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Sample records for 3harachidonic acid release

  1. Release characteristics of polyurethane tablets containing dicarboxylic acids as release modifiers - a case study with diprophylline.

    PubMed

    Claeys, Bart; De Bruyn, Sander; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

    2014-12-30

    The influence of several dicarboxylic acids on the release characteristics of polyurethane tablets with a high drug load was investigated. Mixtures of diprophylline (Dyph) and thermoplastic polyurethane (TPUR) (ratio: 50/50, 65/35 and 75/25 wt.%) were hot-melt extruded and injection molded with the addition of 1, 2.5, 5 and 10% wt.% dicarboxylic acid as release modifier. Incorporating malonic, succinic, maleic and glutaric acid in the TPUR matrices enhanced drug release, proportional to the dicarboxylic acid concentration in the formulation. No correlation was found between the water solubility, melting point, logP and pKa of the acids and their drug release modifying capacity. Succinic and maleic acid had the highest drug release modifying capacity which was linked to more intense molecular interactions with Dyph. A structural fit between the primary and secondary alcohol of Dyph and both carboxylic groups of the acids was at the origin of this enhanced interaction. PMID:25445517

  2. Capture and release of acid-gasses with acid-gas binding organic compounds

    DOEpatents

    Heldebrant, David J; Yonker, Clement R; Koech, Phillip K

    2015-03-17

    A system and method for acid-gas capture wherein organic acid-gas capture materials form hetero-atom analogs of alkyl-carbonate when contacted with an acid gas. These organic-acid gas capture materials include combinations of a weak acid and a base, or zwitterionic liquids. This invention allows for reversible acid-gas binding to these organic binding materials thus allowing for the capture and release of one or more acid gases. These acid-gas binding organic compounds can be regenerated to release the captured acid gasses and enable these organic acid-gas binding materials to be reused. This enables transport of the liquid capture compounds and the release of the acid gases from the organic liquid with significant energy savings compared to current aqueous systems.

  3. Control of arachidonic acid release in chick muscle cultures

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Wright, W.

    1985-01-01

    Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

  4. Release of selected amino acids from zinc carriers.

    PubMed

    Dyja, Renata; Dolińska, Barbara; Ryszka, Florian

    2016-06-01

    The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 μmol of histidine or 17.4 μmol of tryptophan) that provides release of similar amounts of amino acid (4.1-4.6 μmol of histidine or 8.7-9.9 μmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9-11.2 μmol) is limited by the tyrosine low solubility in water. PMID:27279069

  5. Bioerodible devices for intermittent release of simvastatin acid.

    PubMed

    Jeon, Ju Hyeong; Thomas, Mark V; Puleo, David A

    2007-08-01

    The association polymer system of cellulose acetate phthalate (CAP) and Pluronic F-127 (PF-127) was used to create intermittent release devices for mimicking the daily injection of simvastatin that has been reported to stimulate bone formation. To enhance solubility in water, prodrug simvastatin was modified by lactone ring opening, which converts the molecule to its hydroxyacid form. CAP/PF-127 microspheres incorporating simvastatin acid were prepared by a water-acetone-oil-water (W/A/O/W) triple emulsion process. Devices were then fabricated by pressure-sintering UV-treated blank and drug-loaded microspheres. Using a multilayered fabrication approach, pulsatile release profiles were obtained. Delivery was varied by changing loading, number of layers, blend ratio, and incubation conditions. To determine the cellular effects of intermittent exposure to simvastatin acid, MC3T3-E1 cells were cultured with either alternating or sustained concentrations of simvastatin acid in the medium, and DNA content, alkaline phosphatase activity, and osteocalcin secretion were measured. For all three cell responses, cultures exposed to simvastatin acid showed higher activity than did control cultures. Furthermore, cell activity was greater for cells cultured with intermittent concentrations of simvastatin acid compared to cells that were constantly treated. These results imply that devices intermittently releasing simvastatin acid warrant further study for locally promoting osteogenesis. PMID:17433584

  6. Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli.

    PubMed

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2016-01-01

    We previously reported that levels of long-chain fatty acids (FAs) including docosahexaenoic acids (DHA) increase in the hypothalamus of inflammatory pain model mice. However, the precise mechanisms underlying the increment of free fatty acids (FFAs) in the brain during inflammation remains unknown. In this study, we characterized FFAs released by inflammatory stimulation in rat primary cultured astrocytes, and tested the involvement of phospholipase A2 (PLA2) on these mechanisms. Lipopolysaccharide (LPS) stimulation significantly increased the levels of several FAs in the astrocytes. Under these conditions, mRNA expression of cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in LPS-treated group increased compared with the control group. Furthermore, in the culture media, the levels of DHA and arachidonic acid (ARA) significantly increased by LPS stimuli compared with those of a vehicle-treated control group whereas the levels of saturated FAs (SFAs), namely palmitic acid (PAM) and stearic acid (STA), did not change. In summary, our findings suggest that astrocytes specifically release DHA and ARA by inflammatory conditions. Therefore astrocytes might function as a regulatory factor of DHA and ARA in the brain. PMID:27374285

  7. Bis(mesitoyl)phosphinic acid: photo-triggered release of metaphosphorous acid in solution.

    PubMed

    Fast, David E; Zalibera, Michal; Lauer, Andrea; Eibel, Anna; Schweigert, Caroline; Kelterer, Anne-Marie; Spichty, Martin; Neshchadin, Dmytro; Voll, Dominik; Ernst, Hanna; Liang, Yu; Dietliker, Kurt; Unterreiner, Andreas-Neil; Barner-Kowollik, Christopher; Grützmacher, Hansjörg; Gescheidt, Georg

    2016-08-01

    Bis(mesitoyl)phosphinic acid and its sodium salt display a unique photo-induced reactivity: both derivatives stepwise release two mesitoyl radicals and, remarkably, metaphosphorous acid (previously postulated as transient species in the gas phase), providing a new phosphorus-based reagent. PMID:27431207

  8. Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.

    PubMed

    Miyajima, M; Koshika, A; Okada, J; Ikeda, M

    1999-08-01

    The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium. PMID:10425326

  9. Microbial community potentially responsible for acid and metal release from an Ostrobothnian acid sulfate soil

    PubMed Central

    Wu, Xiaofen; Lim Wong, Zhen; Sten, Pekka; Engblom, Sten; Österholm, Peter; Dopson, Mark; Nakatsu, Cindy

    2013-01-01

    Soils containing an approximately equal mixture of metastable iron sulfides and pyrite occur in the boreal Ostrobothnian coastal region of Finland, termed ‘potential acid sulfate soil materials’. If the iron sulfides are exposed to air, oxidation reactions result in acid and metal release to the environment that can cause severe damage. Despite that acidophilic microorganisms catalyze acid and metal release from sulfide minerals, the microbiology of acid sulfate soil (ASS) materials has been neglected. The molecular phylogeny of a depth profile through the plough and oxidized ASS layers identified several known acidophilic microorganisms and environmental clones previously identified from acid- and metal-contaminated environments. In addition, several of the 16S rRNA gene sequences were more similar to sequences previously identified from cold environments. Leaching of the metastable iron sulfides and pyrite with an ASS microbial enrichment culture incubated at low pH accelerated metal release, suggesting microorganisms capable of catalyzing metal sulfide oxidation were present. The 16S rRNA gene analysis showed the presence of species similar to Acidocella sp. and other clones identified from acid mine environments. These data support that acid and metal release from ASSs was catalyzed by indigenous microorganisms adapted to low pH. PMID:23369102

  10. Production of ascorbic acid releasing biomaterials for pelvic floor repair

    PubMed Central

    Mangır, Naşide; Bullock, Anthony J.; Roman, Sabiniano; Osman, Nadir; Chapple, Christopher; MacNeil, Sheila

    2016-01-01

    Objective An underlying abnormality in collagen turnover is implied in the occurrence of complications and recurrences after mesh augmented pelvic floor repair surgeries. Ascorbic acid is a potent stimulant of collagen synthesis. The aim of this study is to produce ascorbic acid releasing poly-lactic acid (PLA) scaffolds and evaluate them for their effects on extracellular matrix production and the strength of the materials. Materials and methods Scaffolds which contained either l-ascorbic acid (AA) and Ascorbate-2-Phosphate (A2P) were produced with emulsion electrospinning. The release of both drugs was measured by UV spectrophotometry. Human dermal fibroblasts were seeded on scaffolds and cultured for 2 weeks. Cell attachment, viability and total collagen production were evaluated as well as mechanical properties. Results No significant differences were observed between AA, A2P, Vehicle and PLA scaffolds in terms of fibre diameter and pore size. The encapsulation efficiency and successful release of both AA and A2P were demonstrated. Both AA and A2P containing scaffolds were significantly more hydrophilic and stronger in both dry and wet states compared to PLA scaffolds. Fibroblasts produced more collagen on scaffolds containing either AA or A2P compared to cells grown on control scaffolds. Conclusion This study is the first to directly compare the two ascorbic acid derivatives in a tissue engineered scaffold and shows that both AA and A2P releasing electrospun PLA scaffolds increased collagen production of fibroblasts to similar extents but AA scaffolds seemed to be more hydrophilic and stronger compared to A2P scaffolds. Statement of significance Mesh augmented surgical repair of the pelvic floor currently relies on non-degradable materials which results in severe complications in some patients. There is an unmet and urgent need for better pelvic floor repair materials. Our current understanding suggests that the ideal material should be able to better

  11. Chemical evolution. XXI - The amino acids released on hydrolysis of HCN oligomers

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Wos, J. D.; Nooner, D. W.; Oro, J.

    1974-01-01

    Major amino acids released by hydrolysis of acidic and basic HCN oligomers are identified by chromatography as Gly, Asp, and diaminosuccinic acid. Smaller amounts of Ala, Ile and alpha-aminoisobutyric acid are also detected. The amino acids released did not change appreciably when the hydrolysis medium was changed from neutral to acidic or basic. The presence of both meso and d, l-diaminosuccinic acids was established by paper chromatography and on an amino acid analyzer.

  12. Development of a controlled release of salicylic acid loaded stearic acid-oleic acid nanoparticles in cream for topical delivery.

    PubMed

    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

  13. 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

  14. Hormonal Regulation of Organic and Phosphoric Acid Release by Barley Aleurone Layers and Scutella.

    PubMed Central

    Drozdowicz, Y. M.; Jones, R. L.

    1995-01-01

    The release of acid from the aleurone layer and scutellum of barley (Hordeum vulgare L. cv Himalaya) was investigated. Aleurone layers isolated from mature barley grains acidify the external medium by releasing organic and phosphoric acids. Gibberellic acid and abscisic acid stimulate acid release 2-fold over control tissue incubated in 10 mM CACl2. Gibberellic acid causes medium acidification by stimulating the release of phosphoric and citric acids, whereas abscisic acid stimulates the release of malic acid. The accumulation of these acids in the incubation medium buffers the medium against changes in pH, particularly between pH 4 and 5. The amounts of amino acids that accumulate in the medium are low (2-12 nmol/layer) compared to other organic and phosphoric acids (100-500 nmol/layer). The scutellum does not play a major role in medium acidification but participates in the uptake of organic acids. The organic acid composition of the starchy endosperm changes after 3 d of imbibition; malic, succinic, and lactic acids decrease, whereas citric and phosphoric acids remain unchanged or increase. These results indicate that during postgerminative growth, the acidity of the starchy endosperm is maintained by acid production by the aleurone layer. PMID:12228509

  15. Metal release from fly ash upon leaching with sulfuric acid or acid mine drainage

    SciTech Connect

    Skousen, J.; Bhumbla, D.K.

    1998-12-31

    Generation of electricity by coal-fired power plants produces large quantities of bottom ash and fly ash. New power plants commonly use fluidized bed combustion (FBC) boilers, which create ashes with high neutralization potential (NP). These ashes, due to their alkaline nature, are often used in surface mine reclamation to neutralize acidity and reduce hydraulic conductivity of disturbed overburdens. Conventional fly ashes from older power plants exhibit a range of pH and NP, with some ashes having neutral or acidic pH and low NP values, and may not be good candidates for supplying alkalinity in reclamation projects. In this study, the authors used two acidic solutions to leach a low NP fly ash (LNP ash) and two FBC ashes (FBC1 and FBC2). After passing 78 pore volumes of sulfuric acid and 129 pore volumes of acid mine drainage (AMD) through these ash materials several trace elements were found at high levels in the leachates. LNP fly ash leachates had high arsenic and selenium concentrations with sulfuric acid leaching, but showed low arsenic and selenium concentrations after leaching with AMD. Leaching with AMD caused the iron and aluminum inherent in AMD to complex these elements and make them unavailable for leaching. Lead, cadmium, and barium concentrations in fly ash leachates were not high enough to cause water pollution problems with either leaching solution. For both leaching solutions, manganese was released from LNP ash at a constant level, FBC1 ash did not release manganese, and FBC2 ash released manganese only after the NP had been exhausted by >60 pore volumes of leaching.

  16. Risk of hydrocyanic acid release in the electroplating industry.

    PubMed

    Piccinini, N; Ruggiero, G N; Baldi, G; Robotto, A

    2000-01-01

    This paper suggests assessing the consequences of hydrocyanic acid (HCN) release into the air by aqueous cyanide solutions in abnormal situations such as the accidental introduction of an acid, or the insertion of a cyanide in a pickling bath. It provides a well-defined source model and its resolution by methods peculiar to mass transport phenomena. The procedure consists of four stages: calculation of the liquid phase concentration, estimate of the HCN liquid-vapour equilibrium, determination of the mass transfer coefficient at the liquid-vapour interface, evaluation of the air concentration of HCN and of the damage distances. The results show that small baths operating at high temperatures are the major sources of risk. The building up of lethal air concentrations, on the other hand, is governed by the values of the mass transfer coefficient, which is itself determined by the flow dynamics and bath geometry. Concerning the magnitude of the risk, the fallout for external emergency planning is slight in all the cases investigated. PMID:10677671

  17. Proliferation-dependent changes in release of arachidonic acid from endothelial cells.

    PubMed Central

    Whatley, R E; Satoh, K; Zimmerman, G A; McIntyre, T M; Prescott, S M

    1994-01-01

    Stimulation of endothelial cells resulted in release of arachidonic acid from phospholipids. The magnitude of this response decreased as the cells became confluent and the change coincided with a decrease in the percentage of cells in growth phases (G2+M); this was not a consequence of time in culture or a factor in the growth medium. Preconfluent cells released approximately 30% of arachidonic acid; confluent cells released only 6%. The decreasing release of arachidonic acid was demonstrated using metabolic labeling, mass measurements of arachidonic acid, and measurement of PGI2. The decrease was not due to a changing pool of arachidonic acid, and mass measurements showed no depletion of arachidonic acid. Release from each phospholipid and from each phospholipid class decreased with confluence. Conversion of confluent cells to the proliferative phenotype by mechanical wounding of the monolayer caused increased release of arachidonic acid. Potential mechanisms for these changes were investigated using assays of phospholipase activity. Phospholipase A2 activity changed in concert with the alteration in release, a consequence of changes in phosphorylation of the enzyme. The increased release of arachidonic acid from preconfluent, actively dividing cells may have important physiologic implications and may help elucidate mechanisms regulating release of arachidonic acid. Images PMID:7962534

  18. Influence of Organic Acids on Diltiazem HCl Release Kinetics from Hydroxypropyl Methyl Cellulose Matrix Tablets.

    PubMed

    Sateesha, Sb; Rajamma, Aj; Narode, Mk; Vyas, Bd

    2010-07-01

    The matrix tablets of diltiazem hydrochloride were prepared by direct compression using hydroxypropyl methyl cellulose (HPMC) and various amounts (2.5%, 5.0%, 10% and 20%) of citric acid, malic acid and succinic acid. The characterization of physical mixture of drug and organic acids was performed by Infra-red spectroscopy. An organic acid was incorporated to set up a system bringing about gradual release of this drug. The influence of organic acids on the release rate were described by the Peppas equation: M (t) /M(∞) = Kt (n) and Higuchi's equation: Q (t) = K(1)t(1/2). The addition of organic acids and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing amounts of organic acid produced an increase in drug release rate, which showed a good linear relationship between contents of organic acid and drug accumulate release (%) in phosphate buffer, pH 7.4. The drug release increased significantly (P < 0.05) with use of succinic acid in tablet formulation. Increasing amounts of succinic acid above 10% produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a burst release of drug from the matrix. Optimized formulations are found to be stable upon 3-month study. PMID:21042476

  19. Influence of Organic Acids on Diltiazem HCl Release Kinetics from Hydroxypropyl Methyl Cellulose Matrix Tablets

    PubMed Central

    Sateesha, SB; Rajamma, AJ; Narode, MK; Vyas, BD

    2010-01-01

    The matrix tablets of diltiazem hydrochloride were prepared by direct compression using hydroxypropyl methyl cellulose (HPMC) and various amounts (2.5%, 5.0%, 10% and 20%) of citric acid, malic acid and succinic acid. The characterization of physical mixture of drug and organic acids was performed by Infra-red spectroscopy. An organic acid was incorporated to set up a system bringing about gradual release of this drug. The influence of organic acids on the release rate were described by the Peppas equation: M t /M∞ = Kt n and Higuchi’s equation: Q t = K1t1/2. The addition of organic acids and the pH value of medium could notably influence the dissolution behavior and mechanism of drug-release from matrices. Increasing amounts of organic acid produced an increase in drug release rate, which showed a good linear relationship between contents of organic acid and drug accumulate release (%) in phosphate buffer, pH 7.4. The drug release increased significantly (P < 0.05) with use of succinic acid in tablet formulation. Increasing amounts of succinic acid above 10% produced decreasing values of n and increasing values of k, in a linear relationship, which indicated there was a burst release of drug from the matrix. Optimized formulations are found to be stable upon 3-month study. PMID:21042476

  20. Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

    SciTech Connect

    Tao, W.

    1988-01-01

    Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release ({sup 3}H)arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. ({sup 3}H)arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The ({sup 3}H)arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates ({sup 3}H) arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils.

  1. Synthesis and release of fatty acids by human trophoblast cells in culture

    SciTech Connect

    Coleman, R.A.; Haynes, E.B.

    1987-11-01

    In order to determine whether placental cells can synthesize and release fatty acids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fatty acid was rapidly synthesized from (/sup 14/C)acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fatty acids synthesized from (/sup 14/C)acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. (/sup 14/C)acetate was also incorporated into cellular triacylglycerol, phospholipid, and cholesterol, but radiolabeled free fatty acid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with (1-/sup 14/C)oleate; trophoblast cells then released /sup 14/C-labeled fatty acid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fatty acid. Twenty percent of the /sup 14/C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fatty acid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fatty acids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fatty acid metabolism and release.

  2. Novel amino acids: synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs.

    PubMed

    Nortcliffe, Andrew; Botting, Nigel P; O'Hagan, David

    2013-07-28

    The incorporation of furoxan and sydnonimine ring systems into amino acid side chains is demonstrated with the preparation of four novel amino acids which carry these nitric oxide-releasing motifs. N-((4-Nitrophenoxy)carbonyl)-3-phenylsydnonimine 9 and bis(phenylsulfonyl)furoxan 10 are the key intermediates for introducing the heterocycle side chains onto appropriate amine and alcohol functionalities respectively. Furoxan 5 and 7 both displayed NO release based on determination of nitrite production. Orthogonal amino acid protecting group strategies were deployed to demonstrate that the amino acids could be incorporated into peptide frameworks. By way of demonstration the amino acids were placed centrally into several tripeptide motifs. Griess test assays showed that these amino acids released NO in the presence of γ-glutathione (GST). PMID:23753002

  3. Inherently antioxidant and antimicrobial tannic acid release from poly(tannic acid) nanoparticles with controllable degradability.

    PubMed

    Sahiner, Nurettin; Sagbas, Selin; Aktas, Nahit; Silan, Coskun

    2016-06-01

    From a natural polyphenol, Tannic acid (TA), poly(TA) nanoparticles were readily prepared using a single step approach with three different biocompatible crosslinkers; trimethylolpropane triglycidyl ether (TMPGDE), poly(ethylene glycol) diglycidyl ether (PEGGE), and trisodium trimetaphosphate (STMP). P(TA) particles were obtained with controllable diameters between 400 to 800nm with -25mV surface charge. The effect of synthesis conditions, such as the emulsion medium, pH values of TA solution, and the type of crosslinker, on the shape, size, dispersity, yield, and degradability of poly(Tannic Acid) (p(TA)) nanoparticles was systematically investigated. The hydrolytic degradation amount in physiological pH conditions of 5.4, 7.4, and 9.0 at 37.5°C were found to be in the order TMPGDEreleasing media. The highest TA release, 600mg/g, was obtained for TMPGDE-crosslinked p(TA) particles in intestinal pH conditions (pH 9) over 3 days; whereas, a slow and linear TA release profile over almost 30 days was obtained by using PEGGE-crosslinked p(TA) in body fluid pH conditions (pH 7.4). The total phenol content of p(TA) particles was calculated as 70±1μgmL(-1) for 170μgmL(-1) p(TA), and the trolox equivalent antioxidant capacity was found to be 2027±104mM trolox equivalent g(-1). Moreover, p(TA) nanoparticles demonstrated strong antimicrobial effects against common bacterial strains. More interestingly, with a higher concentration of p(TA) particles, higher blood clotting indices were obtained. PMID:26970821

  4. Effect of different polyphenol sources on the efficiency of ellagic acid release by Aspergillus niger.

    PubMed

    Sepúlveda, Leonardo; de la Cruz, Reynaldo; Buenrostro, José Juan; Ascacio-Valdés, Juan Alberto; Aguilera-Carbó, Antonio Francisco; Prado, Arely; Rodríguez-Herrera, Raúl; Aguilar, Cristóbal Noé

    2016-01-01

    Fungal hydrolysis of ellagitannins produces hexahydroxydiphenic acid, which is considered an intermediate molecule in ellagic acid release. Ellagic acid has important and desirable beneficial health properties. The aim of this work was to identify the effect of different sources of ellagitannins on the efficiency of ellagic acid release by Aspergillus niger. Three strains of A. niger (GH1, PSH and HT4) were assessed for ellagic acid release from different polyphenol sources: cranberry, creosote bush, and pomegranate used as substrate. Polyurethane foam was used as support for solid-state culture in column reactors. Ellagitannase activity was measured for each of the treatments. Ellagic acid was quantified by high performance liquid chromatography. When pomegranate polyphenols were used, a maximum value of ellagic acid (350.21 mg/g) was reached with A. niger HT4 in solid-state culture. The highest amount of ellagitannase (5176.81 U/l) was obtained at 8h of culture when cranberry polyphenols and strain A. niger PSH were used. Results demonstrated the effect of different polyphenol sources and A. niger strains on ellagic acid release. It was observed that the best source for releasing ellagic acid was pomegranate polyphenols and A. niger HT4 strain, which has the ability to degrade these compounds for obtaining a potent bioactive molecule such as ellagic acid. PMID:26916811

  5. The effects of anaesthetics on the uptake and release of amino acid neurotransmitters in thalamic slices.

    PubMed Central

    Kendall, T. J.; Minchin, M. C.

    1982-01-01

    1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesthetics used had any detectable effect upon the spontaneous release of either amino acid. 4 Urethane and ketamine had no effect upon the K+-stimulated release of either amino acid. 5 Methohexitone and thiopentone produced a biphasic dose-response on the K+-stimulated release of both amino acids; low concentrations enhanced release, high concentrations depressed release. 6 Bicuculline hydrochloride and picrotoxin both significantly reduced the barbiturate-induced enhancement of K+-stimulated amino acid release, but did not significantly alter the depression of K+-stimulated release at higher barbiturate concentrations. 7 Baclofen, either alone (1 microM to 1 mM), or tested against the barbiturates, had no detectable effect. PMID:6122480

  6. Release of brain amino acids during hyposmolar stress and energy deprivation.

    PubMed

    Haugstad, T S; Langmoen, I A

    1996-04-01

    The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p < 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p < 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p < 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p < 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p < 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic > neutral > basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress. PMID:8829565

  7. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120

    PubMed Central

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-01-01

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion. PMID:25915115

  8. Amino Acid Transporters and Release of Hydrophobic Amino Acids in the Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120.

    PubMed

    Pernil, Rafael; Picossi, Silvia; Herrero, Antonia; Flores, Enrique; Mariscal, Vicente

    2015-01-01

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can use inorganic compounds such as nitrate or ammonium as nitrogen sources. In the absence of combined nitrogen, it can fix N2 in differentiated cells called heterocysts. Anabaena also shows substantial activities of amino acid uptake, and three ABC-type transporters for amino acids have been previously characterized. Seven new loci encoding predicted amino acid transporters were identified in the Anabaena genomic sequence and inactivated. Two of them were involved in amino acid uptake. Locus alr2535-alr2541 encodes the elements of a hydrophobic amino acid ABC-type transporter that is mainly involved in the uptake of glycine. ORF all0342 encodes a putative transporter from the dicarboxylate/amino acid:cation symporter (DAACS) family whose inactivation resulted in an increased uptake of a broad range of amino acids. An assay to study amino acid release from Anabaena filaments to the external medium was set up. Net release of the alanine analogue α-aminoisobutyric acid (AIB) was observed when transport system N-I (a hydrophobic amino acid ABC-type transporter) was engaged in the uptake of a specific substrate. The rate of AIB release was directly proportional to the intracellular AIB concentration, suggesting leakage from the cells by diffusion. PMID:25915115

  9. EPA releases study describing potential acid rain damage

    SciTech Connect

    Not Available

    1989-11-01

    The U.S. Environmental Protection Agency's acid rain researchers on August 24 offered evidence that if sulfur emissions are not reduced in the future, aquatic systems in the South will suffer damage from acid rain. Evidence also indicates that reductions in sulfur emissions could improve the health of damaged lakes in the Northeast. The study Future Effects of Long-Term Sulfur Deposition on Surface Water Chemistry: The Direct/Delayed Response Project, developed 50-year projections of watershed quality under three plausible acidic deposition, or acid rain, scenarios. Three areas were studied - the Northeast, comprising all of New England and parts of New York and Pennsylvania; the Mid-Appalachian Region, covering much of Pennsylvania, Maryland, Virginia, and West Virginia; and the Southern Blue Ridge Province, an area covering parts of North Carolina, Tennessee, South Carolina and Georgia. The study is a key element in the closing months of the 10-year National Acid Precipitation Assessment Program.

  10. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    PubMed Central

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  11. [Effect of cholinomimetics on L-glutamic acid release and uptake in the neostriatum of rats].

    PubMed

    Godukhin, O V; Budantsev, A Iu; Selifonova, O V; Agapova, V N

    1983-12-01

    The effects of cholinomimetics on release and uptake of exogenic glutamic acid in the rat brain neostriatum in vivo and in vitro were studied. Carbocholine and nicotin were shown to inhibit the release, carbocholine acting directly on the presynaptic receptors whereas nicotin acting indirectly through the interneurons of neostriatum. PMID:6141074

  12. Vasopressin induces release of arachidonic acid from vascular smooth muscle cells

    SciTech Connect

    Grillone, L.R.; Clark, M.A.; Heckman, G.; Schmidt, D.; Stassen, F.L.; Crooke, S.T.

    1986-05-01

    Cultured smooth muscle cells (A-10), derived from rat thoracic aorta, have vascular (V/sub 1/) vasopressin receptors. They have previously shown that these receptors mediate phosphatidylinositol turnover, Ca/sup 2 +/ efflux, and inhibition of isoproterenol-induced increases in cAMP. Here they studied the effect of vasopressin on arachidonic acid metabolism of A-10 cells. Cells were incubated for 18-20 hr with (/sup 3/H)-arachidonic acid (80 Ci/mmol). Vasopressin stimulated release of arachidonic acid in a time- and dose-dependent manner. Significant release of arachidonic acid was observed after 4 min with 10/sup -9/ M vasopressin. Maximum release was reached 4 min after addition of 10/sup -7/ M vasopressin (1100 dpm/10/sup 6/ cells). About 800 dmp were released after 1 and 4 min with 10/sup -7/ M and 10/sup -8/ M vasopressin, respectively. The vasopressin-stimulated release of arachidonic acid was blocked by the specific V/sub 1//V/sub 2/ vasopressin antagonist d(CH2)5D-Tyr(Et)VAVP. These data indicate that vascular smooth muscle cells increase arachidonic acid release in response to vasopressin. This response is likely mediated by V/sub 1/ receptors.

  13. Capture and release of mixed acid gasses with binding organic liquids

    DOEpatents

    Heldebrant, David J.; Yonker, Clement R.

    2010-09-21

    Reversible acid-gas binding organic liquid systems that permit separation and capture of one or more of several acid gases from a mixed gas stream, transport of the liquid, release of the acid gases from the ionic liquid and reuse of the liquid to bind more acid gas with significant energy savings compared to current aqueous systems. These systems utilize acid gas capture compounds made up of strong bases and weak acids that form salts when reacted with a selected acid gas, and which release these gases when a preselected triggering event occurs. The various new materials that make up this system can also be included in various other applications such as chemical sensors, chemical reactants, scrubbers, and separators that allow for the specific and separate removal of desired materials from a gas stream such as flue gas.

  14. Influence of the Surface Acidity of the Alumina on the Sustained Release of Ketoprofen.

    PubMed

    San Roman, Soledad; Gullón, Jesús; Del Arco, Margarita; Martín, Cristina

    2016-07-01

    This work reports the immobilization of ketoprofen into mesoporous alumina, prepared in different way, to assess their possible applications as a matrix for controlled drug release. The acids' surface properties of the aluminas and their effect on the drug content and release rate were also analyzed. The systems have been characterized by powder X-ray diffractometry, Fourier transformer infrared spectroscopy (FT-IR), N2 adsorption desorption, transmission electron microscopy, and FT-IR of pyridine adsorption. The results show that the drug is incorporated inside the pores of mesoporous alumina, and the content and release rate depend of surface acidity, when increase the surface acidity decrease the drug content and increase the release rate. PMID:27287518

  15. Influence of enteric citric acid on the release profile of 4-aminopyridine from HPMC matrix tablets.

    PubMed

    Martínez González, Ilona; Villafuerte Robles, Leopoldo

    2003-01-30

    A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to study the influence of enteric citric acid (ECA) on the release profile from hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about gradual release of the drug. For this purpose, powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using first 900 ml HCl 0.1 N, and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf)=kt(n). As physically expected, increasing proportions (2-9%) of the in acid insoluble ECA decreased the release rate. In an acid medium, ECA acts as a physical barrier obstructing the diffusion path, dissolving after the pH change to 7.4. Both circumstances flattening the release profile. Apparent zero order release was observed at ECA concentrations of about 10%. The presence of ECA compensates the effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA proportions (10-50%) act increasing the dissolution rate. This is attributed to a void space formation around the insoluble ECA, after HPMC hydration, which percolates after a critical ECA proportion of approximately 10%. Moreover, decreasing release constant values (k) show a logarithmic relationship with increasing values of the exponent (n). This indicates that an apparent zero-order release can be obtained at a given release constant. PMID:12527188

  16. In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust

    SciTech Connect

    Thomson, T.A.; Edwards, J.H.; Al-Zubaidy, T.S.; Brown, R.C.; Poole, A.; Nicholls, P.J.

    1986-04-01

    It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms.

  17. Ethyl cellulose microcapsules for protecting and controlled release of folic acid.

    PubMed

    Prasertmanakit, Satit; Praphairaksit, Nalena; Chiangthong, Worawadee; Muangsin, Nongnuj

    2009-01-01

    Ethyl cellulose microcapsules were developed for use as a drug-delivery device for protecting folic acid from release and degradation in the undesirable environmental conditions of the stomach, whilst allowing its release in the intestinal tract to make it available for absorption. The controlled release folic acid-loaded ethyl cellulose microcapsules were prepared by oil-in-oil emulsion solvent evaporation using a mixed solvent system, consisting of a 9:1 (v/v) ratio of acetone:methanol and light liquid paraffin as the dispersed and continuous phase. Span 80 was used as the surfactant to stabilize the emulsion. Scanning electron microscopy revealed that the microcapsules had a spherical shape. However, the particulate properties and in vitro release profile depended on the concentrations of the ethyl cellulose, Span 80 emulsifier, sucrose (pore inducer), and folic acid. The average diameter of the microcapsules increased from 300 to 448 microm, whilst the folic acid release rate decreased from 52% to 40%, as the ethyl cellulose concentration was increased from 2.5% to 7.5% (w/v). Increasing the Span 80 concentration from 1% to 4% (v/v) decreased the average diameter of microcapsules from 300 to 141 microm and increased the folic acid release rate from 52% to 79%. The addition of 2.5-7.5% (w/v) of sucrose improved the folic acid release from the microcapsules. The entrapment efficiency was improved from 64% to 88% when the initial folic acid concentration was increased from 1 to 3 mg/ml. PMID:19763838

  18. pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles

    PubMed Central

    Häuser, Manuel; Langer, Klaus

    2015-01-01

    Summary Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative. PMID:26885463

  19. Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid

    NASA Technical Reports Server (NTRS)

    Somogyi, Dezso; Feiler, Charles E.

    1960-01-01

    The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

  20. Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules.

    PubMed

    Tan, Yinhe; Si, Xiaoqing; Zhong, Lulu; Feng, Xin; Yang, Xinmin; Huang, Min; Wu, Chuanbin

    2016-10-01

    Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle. PMID:27066697

  1. Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

    PubMed

    Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

    2014-01-01

    Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules. PMID:24060930

  2. Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules

    PubMed Central

    Tan, Yinhe; Si, Xiaoqing; Zhong, Lulu; Feng, Xin; Yang, Xinmin; Huang, Min; Wu, Chuanbin

    2016-01-01

    Abstract Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX® Sprinkle (RAB) delayed-release capsules (ACIPHEX® Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX® Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX® Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX® Sprinkle. PMID:27066697

  3. Depolarization-induced release of amino acids from the vestibular nuclear complex.

    PubMed

    Godfrey, Donald A; Sun, Yizhe; Frisch, Christopher; Godfrey, Matthew A; Rubin, Allan M

    2012-04-01

    There is evidence from immunohistochemistry, quantitative microchemistry, and pharmacology for several amino acids as neurotransmitters in the vestibular nuclear complex (VNC), including glutamate, γ-aminobutyrate (GABA), and glycine. However, evidence from measurements of release has been limited. The purpose of this study was to measure depolarization-stimulated calcium-dependent release of amino acids from the VNC in brain slices. Coronal slices containing predominantly the VNC were prepared from rats and perfused with artificial cerebrospinal fluid (ACSF) in an interface chamber. Fluid was collected from the chamber just downstream from the VNC using a microsiphon. Depolarization was induced by 50 mM potassium in either control calcium and magnesium concentrations or reduced calcium and elevated magnesium. Amino acid concentrations in effluent fluid were measured by high performance liquid chromatography. Glutamate release increased fivefold during depolarization in control calcium concentration and twofold in low calcium/high magnesium. These same ratios were 6 and 1.5 for GABA, 2 and 1.3 for glycine, and 2 and 1.5 for aspartate. Differences between release in control and low calcium/high magnesium ACSF were statistically significant for glutamate, GABA, and glycine. Glutamine release decreased during and after depolarization, and taurine release slowly increased. No evidence for calcium-dependent release was found for serine, glutamine, alanine, threonine, arginine, taurine, or tyrosine. Our results support glutamate and GABA as major neurotransmitters in the VNC. They also support glycine as a neurotransmitter and some function for taurine. PMID:22147284

  4. Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

    PubMed

    Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

    2014-11-19

    A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples. PMID:25369799

  5. Biochemical characterization of polyunsaturated fatty acid synthesis in Schizochytrium: release of the products as free fatty acids.

    PubMed

    Metz, James G; Kuner, Jerry; Rosenzweig, Bradley; Lippmeier, James C; Roessler, Paul; Zirkle, Ross

    2009-06-01

    In marine bacteria and some thraustochytrids (marine stramenopiles) long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced de novo by PUFA synthases. These large, multi-domain enzymes carry out the multitude of individual reactions required for conversion of malonyl-CoA to the final LC-PUFA products. Here we report on the release of fatty acids from the PUFA synthase found in Schizochytrium, a thraustochytrid that has been developed as a commercial source for DHA-enriched biomass and oil. Data from in vitro activity assays indicate that the PUFAs are released from the enzyme as free fatty acids (FFAs). Addition of ATP and Mg(2+) to in vitro assays facilitates appearance of radiolabel from (14)C-malonyl-CoA in a triacylglycerol fraction, suggesting the involvement of acyl-CoA synthetases (ACS). Furthermore, addition of triascin C, an inhibitor of ACSs, to the assays blocks this conversion. When the Schizochytrium PUFA synthase is expressed in Escherichia coli, the products of the enzyme accumulate as FFAs, suggesting that the thioesterase activity required for fatty acid release is an integral part of the PUFA synthase. PMID:19272783

  6. Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

    NASA Astrophysics Data System (ADS)

    Kou, Jim Hwai-Cher

    In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling

  7. Arachidonic acid release and prostaglandin synthesis in a macrophage-like cell line exposed to asbestos.

    PubMed

    Brown, R C; Poole, A

    1984-10-01

    A macrophage-like cell line (P388D1) has been treated with asbestos and the release of arachidonic acid and its metabolites has been studied using two methods. In the first monolayer cultures of the cells were labelled with tritiated arachidonic acid and the release of label into the medium was quantified: secondly the synthesis and release of prostaglandins E2 and F2 alpha were followed using radioimmune assay. Crocidolite asbestos caused the greatest release of tritium while the medium from chrysotile-treated cultures contained more of both prostaglandins. Both of the fibrous dusts were significantly more active in both test systems than were the two 'inert' materials--titanium dioxide and milled sample of crocidolite. It is suggested that these phenomena are due to the effect of mineral dusts on phospholipase activity and that differences in this activity are associated with differences in the pathogenicity of various mineral dusts. PMID:6098173

  8. Epoxyeicosatrienoic Acids (EETs) are Endogenous Regulators of Vasoactive Neuropeptide Release from Trigeminal Ganglion Neurons

    PubMed Central

    Iliff, Jeffrey J.; Fairbanks, Stacy L.; Balkowiec, Agnieszka; Alkayed, Nabil J.

    2010-01-01

    Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of CYP-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. Herein we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for one hour with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K+ (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K+ stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, while in the presence of 14,15-EEZE K+-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p<0.01 ANOVA, n=6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p<0.05 ANOVA, n=6). Similarly, pre-treatment with the CYP epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage. PMID:20950340

  9. Epoxyeicosatrienoic acids are endogenous regulators of vasoactive neuropeptide release from trigeminal ganglion neurons.

    PubMed

    Iliff, Jeffrey J; Fairbanks, Stacy L; Balkowiec, Agnieszka; Alkayed, Nabil J

    2010-12-01

    Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. We previously described the expression of cytochrome P450-2J epoxygenase in rat trigeminal ganglion neurons and that EETs signaling is involved in cerebrovascular dilation resulting from perivascular nerve stimulation. In this study, we evaluate the presence of the EETs signaling pathway in trigeminal ganglion neurons and their role in modulating the release of calcitonin gene-related peptide (CGRP) by trigeminal ganglion neurons. Liquid chromatography tandem mass spectrometry identified the presence of each of the four EETs regio-isomers within primary trigeminal ganglion neurons. Stimulation for 1 h with the transient receptor potential vanilloid-1 channel agonist capsaicin (100 nmol/L) or depolarizing K(+) (60 mmol/L) increased CGRP release as measured by ELISA. Stimulation-evoked CGRP release was attenuated by 30 min pre-treatment with the EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol/L). K(+) stimulation elevated CGRP release 2.9 ± 0.3-fold above control levels, whereas in the presence of 14,15-EEZE K(+)-evoked CGRP release was significantly reduced to 1.1 ± 0.2-fold above control release (p < 0.01 anova, n = 6). 14,15-EEZE likewise attenuated capsaicin-evoked CGRP release from trigeminal ganglion neurons (p < 0.05 anova, n = 6). Similarly, pre-treatment with the cytochrome P450 epoxygenase inhibitor attenuated stimulation-evoked CGRP release. These data demonstrate that EETs are endogenous constituents of rat trigeminal ganglion neurons and suggest that they may act as intracellular regulators of neuropeptide release, which may have important clinical implications for treatment of migraine, stroke and vasospasm after subarachnoid hemorrhage. PMID:20950340

  10. Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

    PubMed

    Arcan, Iskender; Yemenicioğlu, Ahmet

    2014-08-13

    To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food. PMID:25025594

  11. Controlled protein release from polyethyleneimine-coated poly(L-lactic acid)/pluronic blend matrices.

    PubMed

    Park, T G; Cohen, S; Langer, R

    1992-01-01

    Protein release from degradable polymer matrices, composed of poly(L-lactic acid) and its blends with Pluronic surfactant, was investigated with and without the aqueous coating of an adsorptive water-soluble polymer, polyethyleneimine (PEI). PEI is a highly branched cationic polymer containing primary, secondary, and tertiary amino groups in its backbone. The treatment of PEI for PLA/Pluronic blend films exhibited a remarkable decrease in the "burst" release of protein at an initial stage and a significant extension in the protein release period. Protein release profiles could be controlled by varying PEI treatment time and its concentration. Our results suggest that PEI diffuses into the polymer matrices and crosslinks protein molecules by ionic interactions. Such a PEI-protein network near the surface region of matrix may act as a diffusional barrier for further release of protein molecules. PMID:1589407

  12. Photoreactivation of ultraviolet radiation-induced release of arachidonic acid from marsupial cells.

    PubMed

    Kaleta, E W; Applegate, L A; Ley, R D

    1991-11-01

    Exposure of an established marsupial cell line, PtK2 (Potorous tridactylus), to ultraviolet radiation (UVR) from an FS-40 sunlamp (280-400 nm) resulted in a fluence-dependent release of radiolabeled arachidonic acid (AA) from cell membranes. Post-UVR, but not pre-UVR, exposure to photoreactivating light reversed UVR-induced pyrimidine dimers in DNA and suppressed the UVR-induced release of AA. These data indicate that DNA damage contributes to the release of AA from membrane phospholipids. PMID:1665911

  13. Polymer length of teichuronic acid released from cell walls of Micrococcus luteus.

    PubMed Central

    Wolters, P J; Hildebrandt, K M; Dickie, J P; Anderson, J S

    1990-01-01

    Teichuronic acid released from its phosphodiester linkage to peptidoglycan in the cell walls of Micrococcus luteus by mild acid treatment is resolved into a ladderlike series of bands by electrophoresis on polyacrylamide gels in the presence of borate. Each band of the ladder differs from its nearest neighbor by one disaccharide repeat unit, ----4)-2-acetamido-2-deoxy-beta-D-mannopyranuronosyl-(1----6)- alpha-D-glucopyranosyl-(1-. Acid-fragmented teichuronic acid, after conversion to the phenylamine derivative, was fractionated by preparative-scale molecular sieve column chromatography, which produced a series of elution peaks. Fast-atom-bombardment mass spectrometry of the smallest member of the series determined its molecular weight and established its identity as the phenylamine derivative of one disaccharide repeat unit of teichuronic acid. Homologous fractions of the same series were used to index the ladder of bands obtained by polyacrylamide gel electrophoresis from samples containing a more extensive distribution of polymer lengths. Nearly native teichuronic acid consists of polymers with a broad range of molecular sizes ranging from 20 to 55 disaccharide units. The most abundant species are those which have 25 to 40 repeat units. Prolonged treatment of teichuronic acid with the acid conditions used to release it from peptidoglycan causes gradual fragmentation of the teichuronic acid. Images PMID:2394683

  14. The effect of humic acids on the element release from high level waste glass

    SciTech Connect

    Wei, J.; Van Iseghem, P.

    1997-12-31

    Eu and Am doped glasses were interacted with synthetic interstitial clay water (SiC) and corresponding reference leachant, humic acids free interstitial solution (IS) to investigate the influence of humic acids on the leaching behavior of the waste glass. Static leach tests were carried out at 40 C and 90 C. The release of the lanthanide Eu and the actinide Am from the glass was obviously enhanced by the presence of humic acids. The leaching of transition elements, Fe and Ti strongly depends on the humic acids concentration. The leaching of glass matrix components, Al and B was also influenced by the concentrations of humic acids. However, humic acids have little effect on the leaching of glass matrix element Si.

  15. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    SciTech Connect

    Saxena, U.; Witte, L.D.; Goldberg, I.J.

    1989-03-15

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of /sup 125/I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid.

  16. Adenosine inhibition of gamma-aminobutyric acid release from slices of rat cerebral cortex.

    PubMed Central

    Hollins, C.; Stone, T. W.

    1980-01-01

    1 The effect of purine compounds on the potassium-evoked release of 14C-labelled gamma-aminobutyric acid (GABA) has been studied in 400 micrometers slices of rat cerebral cortex in vitro. 2 Adenosine and adenosine 5' monophosphate (AMP) inhibited the release of GABA at 10(-5) to 10(-3) M. Adenosine triphosphate (ATP) produced a significant inhibition of release only at 10(-3) M. 3 Theophylline 10(-4) or 10(-3) M reduced the inhibitory effect of adenosine, but did not change basal release of GABA. 4 Dipyridamole 10(-5) M itself reduced evoked GABA release, but did not prevent the inhibitory effect of adenosine, implying that adenosine was acting at an extracellularly directed receptor. 5 Calcium removal or antagonism by verapamil reduced the evoked release of GABA, but adenosine did not produce any further reduction of the calcium-independent release. This may indicate that the inhibitory effect of adenosine on GABA release results from interference with calcium influx or availability within the terminals. PMID:7378648

  17. Release Kinetic in Yogurt from Gallic Acid Microparticles with Chemically Modified Inulin.

    PubMed

    García, Paula; Vergara, Cristina; Robert, Paz

    2015-10-01

    Gallic acid (GA) was encapsulated with native (NIn), cross-linked (CIn) and acetylated (AIn) inulin by spray-drying. Inulin microparticles were characterized by encapsulation efficiency (EE) and their release profile in yogurt. The EE was significantly higher for GA-CIn (98%) compared with GA-NIn (81%) and GA-AIn (77%) microparticles, showing the effect of the modification of inulin on interaction of GA-polymer. GA release profile data in yogurt for GA-CIn, GA-NIn and GA-AIn were fitted to Peppas and Higuchi models in order to obtain the GA release rate constant. Although the GA release rate constants were significantly different among systems, these differences were slight and the GA release was fast (80% < 2 h) in the three systems, showing that inulin-systems did not control GA release in yogurt. The mechanism of GA release followed a Fickian diffusion and relaxation of chains for all microparticles. According to the release profile, these microparticles would be best suited for use in instant foods. PMID:26305430

  18. Erosive effects of different acids on bovine enamel: release of calcium and phosphate in vitro.

    PubMed

    Hannig, Christian; Hamkens, Arne; Becker, Klaus; Attin, Rengin; Attin, Thomas

    2005-06-01

    The present study intended to investigate minimal erosive effects of different acids on enamel during short time incubation via determination of calcium and phosphate dissolution. Bovine enamel specimens were eroded for 1-5 min with eight different acids of pH 2, 2.3 and 3 (citric (CA), maleic (MA), lactic (LA), tartaric (TA), phosphoric (PA), oxalic (OA), acetic (AA) and hydrochloric acid (HCl)). Calcium (Ca) and phosphate (P) release were determined photometrically using arsenazo III (calcium) and malachite green (phosphate) as substrates. Each subgroup contained eight enamel specimens. Amount of titratable acid was determined for all acidic solutions. MA, LA, TA, AA and HCl caused linear release of Ca and P, PA of Ca, CA of P. For CA, MA, LA, TA, AA, PA and HCl mineral loss was shown to be pH-dependent. Ca dissolution varied between 28.6+/-4.4 (LA, pH 2) and 2.4+/-0.7 nmol mm(-2)min(-1) (HCl, pH 3), P dissolution ranged between 17.2+/-2.6 (LA, pH 2) and 1.4+/-0.4 nmol mm(-2)min(-1) (HCl, pH 3). LA was one of the most erosive acids. AA was very erosive at pH 3. HCl and MA were shown to have the lowest erosive effects. There was only a weak correlation (r=0.28) between P and Ca release and the amount of titratable acid. The method of the present study allows investigation of minimal erosive effects via direct determination of P and Ca dissolution. During short time exposition at constant pH level, erosive effects mainly depend on pH and type of acid but not on amount of titratable acid. PMID:15848147

  19. Disruption of Adenovirus Type 7 by Lithium Iodide Resulting in the Release of Viral Deoxyribonucleic Acid

    PubMed Central

    Neurath, A. Robert; Stasny, John T.; Rubin, Benjamin A.

    1970-01-01

    Adenovirus type 7 exposed to solutions of LiI was progressively converted into slower sedimenting deoxyribonucleic acid (DNA)-containing particles, and, ultimately, under proper conditions, DNA free or almost free from protein was released from the virus. The degree of viral degradation was dependent on the time of treatment, on the temperature, and on the concentration of the reagent. PMID:4988267

  20. Release and consumption of D-amino acids during growth of marine prokaryotes.

    PubMed

    Azúa, Iñigo; Goiriena, Itziar; Baña, Zuriñe; Iriberri, Juan; Unanue, Marian

    2014-01-01

    Analysis of the composition of the marine-dissolved organic matter has highlighted the importance of D-amino acids, whose origin is attributed mainly to the remains of bacterial peptidoglycan released as a result of grazing or viral lysis. However, very few studies have focused on the active release of D-amino acids by bacteria. With this purpose, we measured the concentration of dissolved amino acids in both enantiomeric forms with two levels of complexity: axenic cultures of Vibrio furnissii and Vibrio alginolyticus and microcosms created from marine microbial assemblages (Biscay Bay, Cantabrian Sea) with and without heterotrophic nanoflagellates (HNFs). Axenic cultures showed that only D-Ala was significantly released and accumulated in the medium up to a concentration of 120 nM, probably as a consequence of the rearrangement of peptidoglycan. The marine microbial assemblages showed that only two D-amino acids significantly accumulated in the environment, D-Ala and D-aspartic acid (Asp), in both the absence and presence of HNFs. The D/L ratio increased during the incubation and reached maximum values of 3.0 to 4.3 for Ala and 0.4 to 10.6 for Asp and correlated with prokaryotic and HNF abundance as well as the rate of prokaryotic thymidine and leucine incorporation. Prokaryotes preferentially consumed L-amino acids, but the relative uptake rates of D-Ala significantly increased in the growth phase. These results demonstrate that bacteria can release and consume D-amino acids at high rates during growth, even in the absence of viruses and grazers, highlighting the importance of bacteria as producers of dissolved organic matter (DOM) in the sea. PMID:24057323

  1. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    SciTech Connect

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. )

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  2. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    PubMed Central

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang

    2015-01-01

    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy. PMID:25837468

  3. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo.

    PubMed

    Stelmakienė, Ada; Ramanauskienė, Kristina; Briedis, Vitalis

    2015-06-01

    The aim of this study was to evaluate the release of rosmarinic acid (RA) from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration. PMID:26011936

  4. Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

    PubMed

    Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

    2015-09-01

    This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. PMID:25887216

  5. Enhanced histamine release from lung mast cells of guinea pigs exposed to sulfuric acid aerosols

    SciTech Connect

    Fujimaki, Hidekazu ); Katayama, Noboru; Wakamori, Kazuo )

    1992-06-01

    To clarify the relationship between air pollution and mast cell response, the effects of sulfuric acid aerosols on histamine release from lung mast cells of guinea pigs were investigated. Guinea pigs were exposed to 0.3, 1.0 and 3.2 mg/m{sup 3} sulfuric acid (H{sub 2}SO{sub 4}) aerosols or 4 ppm nitrogen dioxide (NO{sub 2}) for 2 and 4 weeks. After the exposure, lung mast cell suspensions were isolated by collagenase treatment and antigen- or A23187-induced histamine release was measured. Antigen-induced histamine release from mast cells was significantly enhanced by the exposure to 1.0 and 3.2 mg/m{sup 3} H{sub 2}SO{sub 4} for 2 weeks, but exposure to H{sub 2}SO{sub 4} for 4 weeks did not show the enhancement of antigen-induced histamine release. A23187-induced histamine release was significantly enhanced by the exposure to 1.0 mg/m{sup 3} H{sub 2}SO{sub 4} or 4 ppm NO{sub 2} for 2 weeks, but suppression of histamine release from lung mast cells stimulated with A23187 was observed by the exposure to 3.2 mg/m{sup 3} H{sub 2}So{sub 4} for 4 weeks. The exposure to 0.3 mg/m{sup 3} H{sub 2}So{sub 4} showed no changes in antigen- and A23187-induced histamine release. The combination of 1.0 mg/m{sup 3} H{sub 2}So{sub 4} with 4 ppm NO{sub 2} for 2 weeks resulted in no changes in antigen- and A23187-induced histamine release. These results suggested that functional properties of lung mast cells may be altered by a low concentration of H{sub 2}So{sub 4} aerosol exposure.

  6. Spore Cortex Hydrolysis Precedes Dipicolinic Acid Release during Clostridium difficile Spore Germination

    PubMed Central

    Francis, Michael B.; Allen, Charlotte A.

    2015-01-01

    ABSTRACT Bacterial spore germination is a process whereby a dormant spore returns to active, vegetative growth, and this process has largely been studied in the model organism Bacillus subtilis. In B. subtilis, the initiation of germinant receptor-mediated spore germination is divided into two genetically separable stages. Stage I is characterized by the release of dipicolinic acid (DPA) from the spore core. Stage II is characterized by cortex degradation, and stage II is activated by the DPA released during stage I. Thus, DPA release precedes cortex hydrolysis during B. subtilis spore germination. Here, we investigated the timing of DPA release and cortex hydrolysis during Clostridium difficile spore germination and found that cortex hydrolysis precedes DPA release. Inactivation of either the bile acid germinant receptor, cspC, or the cortex hydrolase, sleC, prevented both cortex hydrolysis and DPA release. Because both cortex hydrolysis and DPA release during C. difficile spore germination are dependent on the presence of the germinant receptor and the cortex hydrolase, the release of DPA from the core may rely on the osmotic swelling of the core upon cortex hydrolysis. These results have implications for the hypothesized glycine receptor and suggest that the initiation of germinant receptor-mediated C. difficile spore germination proceeds through a novel germination pathway. IMPORTANCE Clostridium difficile infects antibiotic-treated hosts and spreads between hosts as a dormant spore. In a host, spores germinate to the vegetative form that produces the toxins necessary for disease. C. difficile spore germination is stimulated by certain bile acids and glycine. We recently identified the bile acid germinant receptor as the germination-specific, protease-like CspC. CspC is likely cortex localized, where it can transmit the bile acid signal to the cortex hydrolase, SleC. Due to the differences in location of CspC compared to the Bacillus subtilis germinant

  7. Co-release of acetylcholine and gamma-aminobutyric acid by a retinal neuron

    SciTech Connect

    O'Malley, D.M.; Masland, R.H.

    1989-05-01

    Rabbit retinas were vitally stained with 4',6-diamidino-2-phenylindole (DAPI), a fluorescent compound that selectively accumulates within the cholinergic amacrine cells. The retinas were then incubated in vitro in the presence of radioactive gamma-aminobutyric acid (GABA) and autoradiographed. The cells that accumulated DAPI were found to accumulate GABA, confirming immunohistochemical evidence that the cholinergic amacrine cells contain GABA. Incubation of retinas in the presence of elevated concentrations of K+ caused them to release acetylcholine and GABA, and autoradiography showed depletion of radioactive GABA from the cholinergic amacrine cells. This indicates that the cholinergic amacrine cells can secrete acetylcholine and GABA. Retinas were double-labeled with (14C)GABA and (3H)acetylcholine, allowing simultaneous measurement of their release. The release of (14C)GABA was found to be independent of extracellular Ca2+. Radioactive GABA synthesized endogenously from (14C)glutamate behaved the same way as radioactive GABA accumulated from the medium. In the same experiments the simultaneously measured release of (3H)acetylcholine was strongly Ca2+-dependent, indicating that the releases of acetylcholine and GABA are controlled by different mechanisms. Synaptic vesicles immunologically isolated from double-labeled retinas contained much (3H)acetylcholine and little or no (14C)GABA. These results suggest that the cholinergic amacrine cells release acetylcholine primarily by vesicle exocytosis and release GABA primarily by means of a carrier.

  8. Acacia-gelatin microencapsulated liposomes: preparation, stability, and release of acetylsalicylic acid.

    PubMed

    Dong, C; Rogers, J A

    1993-01-01

    Liposomes of dipalmitoylphosphatidylcholine (DPPC) containing acetylsalicylic acid (ASA) have been microencapsulated by acacia-gelatin using the complex coacervation technique as a potential oral drug delivery system. The encapsulation efficiency of ASA was unaltered by the microencapsulation process. The stability of the microencapsulated liposomes in sodium cholate solutions at pH 5.6 was much greater than the corresponding liposomes. The optimum composition and conditions for stability and ASA release were 3.0% acacia-gelatin and a 1- to 2-hr formaldehyde hardening time. Approximately 25% ASA was released in the first 6 hr from microencapsulated liposomes at 23 degrees C and the kinetics followed matrix-controlled release (Q varies; is directly proportional to t1/2). At 37 degrees C, this increased to 75% released in 30 min followed by a slow constant release, likely due to lowering of the phase transition temperature of DPPC by the acacia-gelatin to near 37 degrees C. At both temperatures, the release from control liposomes was even more rapid. Hardening times of 4 hr and an acacia-gelatin concentration of 5% resulted in a lower stability of liposomes and a faster release of ASA. It is concluded that under appropriate conditions the microencapsulation of liposomes by acacia-gelatin may increase their potential as an oral drug delivery system. PMID:8430052

  9. Controlled release of insulin through hydrogels of (acrylic acid)/trimethylolpropane triacrylate

    NASA Astrophysics Data System (ADS)

    Raymundi, Vanessa C.; Aguiar, Leandro G.; Souza, Esmar F.; Sato, Ana C.; Giudici, Reinaldo

    2015-12-01

    Hydrogels of poly(acrylic acid) crosslinked with trimethylolpropane triacrylate (TMPTA) were produced through solution polymerization. After these hydrogels were loaded with insulin solution, they evidenced swelling. Experiments of controlled release of insulin through the hydrogels were performed in acidic and basic media in order to evaluate the rates of release of this protein provided by the referred copolymer. Additionally, a mathematical description of the system based on differential mass balance was made and simulated in MATLAB. The model consists of a system of differential equations which was solved numerically. As expected, the values of swelling index at the equilibrium and the rates of insulin release were inversely proportional to the degree of crosslinking. The mathematical model provided reliable predictions of release profiles with fitted values of diffusivity of insulin through the hydrogels in the range of 6.0 × 10-7-1.3 × 10-6 cm2/s. The fitted and experimental values of partition coefficients of insulin between the hydrogel and the medium were lower for basic media, pointing out good affinity of insulin for these media in comparison to the acidic solutions.

  10. Sustained release formulation of erythropoietin using hyaluronic acid hydrogels crosslinked by Michael addition.

    PubMed

    Hahn, Sei Kwang; Oh, Eun Ju; Miyamoto, Hajime; Shimobouji, Tsuyoshi

    2006-09-28

    A novel sustained release formulation of erythropoietin (EPO) was successfully developed using hyaluronic acid (HA) hydrogels crosslinked by Michael addition. Adipic acid dihydrazide grafted HA (HA-ADH) was prepared and then modified into methacrylated HA (HA-MA). (1)H NMR analysis showed that the degrees of HA-ADH and HA-MA modification were 69 and 29 mol%, respectively. Using the specific crosslinkers of dithiothreitol (DTT) and peptide linker, EPO was loaded during HA-MA hydrogel preparation by Michael addition chemistry between thiol and methacrylate groups. The amount of EPO recovered from both hydrogels after degradation with hyaluronidase SD (HAse SD) was about 90%. The crosslinking reaction with peptide linker (GCYKNRDCG) was faster than that with DTT. The gelation time was about 30 min for peptide linker and 180 min for DTT. In vitro release test of EPO from HA-MA hydrogel at 37 degrees C showed that EPO was released rapidly for 2 days and then slowly up to 7 days from HA-MA hydrogels. The released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo release test of EPO from HA-MA hydrogels crosslinked with the peptide linker in Sprague-Dawley (SD) rats, elevated plasma concentration of EPO was maintained up to 7 days. There was no adverse effect during and after the in vivo tests. PMID:16781096

  11. Release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) antimicrobial nanofibrous membranes.

    PubMed

    Jiang, Suwei; Lv, Jian; Ding, Man; Li, Yanan; Wang, Hualin; Jiang, Shaotong

    2016-02-01

    The present work aimed to evaluate the release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) (Tet-CS/PLA) antimicrobial nanofibrous membranes fabricated via electrospinning technique. The electrospinning solution was a blend of Tet, CS formic acid solution and PLA chloroform/ethanol solution. The interaction between CS and PLA in CS/PLA nanofibers was confirmed to be hydrogen bond. The incorporation of Tet caused a slight decrease in the diameter of nanofibers with Tet content below 30%. Tet-CS/PLA nanofibrous membrane showed a slight initial burst within the first 4h before a gradual increase in cumulative release, and the release percentage increased with increasing Tet contents. Tet release (Mt/M∞<0.6) from the medicated nanofibers could be described by Fickian diffusion model and the release profiles showed two sequential stages. Tet-CS/PLA nanofibrous membranes exhibited an effective and sustainable inhabitance on the growth of Staphylococcus aureus, and the antimicrobial activity increased rapidly with increasing Tet contents below 20%. Furthermore, the incorporation of Tet promoted the degradation of nanofibrous membranes. PMID:26652352

  12. Lipoxygenase Pathway in Islet Endocrine Cells. OXIDATIVE METABOLISM OF ARACHIDONIC ACID PROMOTES INSULIN RELEASE

    PubMed Central

    Metz, Stewart; VanRollins, Michael; Strife, Robert; Fujimoto, Wilfred; Robertson, R. Paul

    1983-01-01

    Metabolism of arachidonic acid (AA) via the cyclooxygenase pathway reduces glucose-stimulated insulin release. However, metabolism of AA by the lipoxygenase pathway and the consequent effects on insulin secretion have not been simultaneously assessed in the endocrine islet. Both dispersed endocrine cell-enriched pancreatic cells of the neonatal rat, as well as intact islets of the adult rat, metabolized [3H]AA not only to cyclooxygenase products (prostaglandins E2, F2α, and prostacyclin) but also to the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE). 12-HETE was identified by coelution with authentic tritiated or unlabeled 12-HETE using four high performance liquid chromatographic systems under eight mobile-phase conditions and its identity was confirmed by gas chromatography/mass spectrometry using selected ion monitoring. The predominant effect of exogenous AA (5 μg/ml) was to stimulate insulin release from pancreatic cells grown in monolayer. This effect was concentration- and time-dependent, and reversible. The effect of AA upon insulin release was potentiated by a cyclooxygenase inhibitor (indomethacin) and was prevented by either of two lipoxygenase inhibitors (5,8,11,14-eicosatetraynoic acid [ETYA] and BW755c). In addition, glucose, as well as two structurally dissimilar agents (the calcium ionophore A23187 and bradykinin), which activate phospholipase(s) and thereby release endogenous AA in several cell systems, also stimulated insulin secretion. The effects of glucose, glucagon, bradykinin and high concentrations of A23187 (5 μg/ml) to augment insulin release were blocked or considerably reduced by lipoxygenase inhibitors. However, a lower concentration of the ionophore (0.25 μg/ml), which did not appear to activate phospholipase, was resistant to blockade. Exogenous 12-HETE (up to 2,000 ng/ml) did not alter glucose-induced insulin release. However, the labile intermediate 12-hydroperoxy-ETE increased insulin release. Furthermore

  13. Inhibition by somatostatin (growth-hormone release-inhibiting hormone, GH-RIH) of gastric acid and pepsin and G-cell release of gastrin.

    PubMed Central

    Barros D'sa, A A; Bloom, S R; Baron, J H

    1978-01-01

    Somatostatin (cyclic growth-hormone release-inhibiting hormone--GH-RIH) was infused into dogs with gastric fistulae. Somatostatin inhibited gastric acid response to four gastric stimulants--insulin, food, histamine, and pentagastrin. Histamine- and pentagastrin-stimulated pepsins were inhibited similarly to inhibition of acid. Somatostatin inhibited the gastrin response to insulin and food. PMID:348581

  14. OX1 orexin/hypocretin receptor signaling through arachidonic acid and endocannabinoid release.

    PubMed

    Turunen, Pauli M; Jäntti, Maria H; Kukkonen, Jyrki P

    2012-08-01

    We showed previously that OX(1) orexin receptor stimulation produced a strong (3)H overflow response from [(3)H]arachidonic acid (AA)-labeled cells. Here we addressed this issue with a novel set of tools and methods, to distinguish the enzyme pathways responsible for this response. CHO-K1 cells heterologously expressing human OX(1) receptors were used as a model system. By using selective pharmacological inhibitors, we showed that, in orexin-A-stimulated cells, the AA-derived radioactivity was released as two distinct components, i.e., free AA and the endocannabinoid 2-arachidonoyl glycerol (2-AG). Two orexin-activated enzymatic cascades are responsible for this response: cytosolic phospholipase A(2) (cPLA(2)) and diacylglycerol lipase; the former cascade is responsible for part of the AA release, whereas the latter is responsible for all of the 2-AG release and part of the AA release. Essentially only diacylglycerol released by phospholipase C but not by phospholipase D was implicated as a substrate for 2-AG production, although both phospholipases were strongly activated. The 2-AG released acted as a potent paracrine messenger through cannabinoid CB(1) receptors in an artificial cell-cell communication assay that was developed. The cPLA(2) cascade, in contrast, was involved in the activation of orexin receptor-operated Ca(2+) influx. 2-AG was also released upon OX(1) receptor stimulation in recombinant HEK-293 and neuro-2a cells. The results directly show, for the first time, that orexin receptors are able to generate potent endocannabinoid signals in addition to arachidonic acid signals, which may explain the proposed orexin-cannabinoid interactions (e.g., in neurons). PMID:22550093

  15. Adsorption and release of amino acids mixture onto apatitic calcium phosphates analogous to bone mineral

    NASA Astrophysics Data System (ADS)

    El Rhilassi, A.; Mourabet, M.; El Boujaady, H.; Bennani-Ziatni, M.; Hamri, R. El; Taitai, A.

    2012-10-01

    Study focused on the interaction of adsorbate with poorly crystalline apatitic calcium phosphates analogous to bone mineral. Calcium phosphates prepared in water-ethanol medium at physiological temperature (37 °C) and neutral pH, their Ca/P ratio was between 1.33 and 1.67. Adsorbate used in this paper takes the mixture form of two essential amino acids L-lysine and DL-leucine which have respectively a character hydrophilic and hydrophobic. Adsorption and release are investigated experimentally; they are dependent on the phosphate type and on the nature of adsorbate L-lysine, DL-leucine and their mixture. Adsorption of mixture of amino acids on the apatitic calcium phosphates is influenced by the competition between the two amino acids: L-lysine and DL-leucine which exist in the medium reaction. The adsorption kinetics is very fast while the release kinetics is slow. The chemical composition of apatite has an influence on both adsorption and release. The interactions adsorbate-adsorbent are electrostatic type. Adsorption and release reactions of the amino acid mixture are explained by the existence of the hydrated surface layer of calcium phosphate apatite. The charged sbnd COOsbnd and sbnd NH3+ of adsorbates are the strongest groups that interact with the surface of apatites, the adsorption is mainly due to the electrostatic interaction between the groups sbnd COOsbnd of amino acids and calcium Ca2+ ions of the apatite. Comparative study of interactions between adsorbates (L-lysine, DL-leucine and their mixture) and apatitic calcium phosphates is carried out in vitro by using UV-vis and infrared spectroscopy IR techniques.

  16. Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF)-release induced by interleukin-1 from superfused rat hypothalami.

    PubMed

    Cambronero, J C; Rivas, F J; Borrell, J; Guaza, C

    1992-07-01

    The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypoxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE2 failed to induce increases on CRF release, PGF2 alpha stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2 alpha could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1. PMID:1619039

  17. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors.

    PubMed

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J; Gribble, Fiona M; Reimann, Frank

    2015-11-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

  18. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

    PubMed Central

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.; Glass, Leslie L.; Schoonjans, Kristina; Holst, Jens J.

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

  19. Layered double hydroxides as supports for the slow release of acid herbicides.

    PubMed

    Cardoso, Lucelena P; Celis, Rafael; Cornejo, Juan; Valim, João B

    2006-08-01

    A Mg/Al layered double hydroxide (LDH) was intercalated with the anionic herbicides 2,4-D, MCPA, and picloram by using three different methodologies: (i) direct synthesis (DS), (ii) regeneration (RE), and (iii) ion exchange (IE). The resulting complexes were characterized and assayed by batch release and column leaching tests, aiming at the controlled release of these herbicides. All the tested LDH-herbicide complexes displayed similar slow herbicide release properties in water, although the IE method seemed to result in complexes with a greater fraction of herbicide in a readily available form. Apparently, the LDH-herbicide complexes released most of the active ingredient present in the complexes at the end of the batch release experiment. This was attributed to the replacement of the intercalated herbicide by carbonate and hydroxyl anions from the aqueous solution. Compared to the free herbicides, the application of the three LDH-herbicide complexes (RE) to soil columns resulted in reduction in the maximum herbicide concentration in leachates and led to the retardation of herbicide leaching through the soil. All LDH-herbicide complexes presented an herbicidal efficacy similar to that of the free (technical) herbicides. Our results indicated the potential applicability of LDHs as supports for the preparation of slow release formulations of acid herbicides such as 2,4-D, MCPA, or picloram. PMID:16881703

  20. Structural characterization of lyotropic liquid crystals containing a dendrimer for solubilization and release of gallic acid.

    PubMed

    Bitan-Cherbakovsky, Liron; Aserin, Abraham; Garti, Nissim

    2013-12-01

    The role of 2nd generation polypropyleneimine (PPIG2) dendrimer in controlling the release of gallic acid (GA) as a model drug from lyotropic liquid crystal was explored. GA (0.2wt%) was solubilized in three types of mesophases: lamellar (Lα), cubic (space group of Ia3d, Q(G)), and reverse hexagonal (HII), composed of GMO and water (and d-α-tocopherol, or tricaprylin in the case of HII mesophases). Small angle X-ray scattering (SAXS) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) along with UV spectrophotometry were utilized to elucidate the structure modifications and release resulting from the cosolubilization of GA and PPIG2. Solubilization of PPIG2 into Lα and Q(G) phases caused transformation of both structures to HII. The diffusion of GA out of the mesophases was found to be dependent on water content and PPIG2 concentration. Rapid release from Lα+PPIG2 and Q(G)+PPIG2 mesophases was recorded. The release from both HII mixtures (with d-α-tocopherol and tricaprylin) was shown to be dependent on the type of oil. Release studies conducted for 72h showed that GA release can be modulated and sustained by the presence of PPIG2, supposedly due to the electrostatic interactions between the dendrimer and the drug molecule. PMID:23973908

  1. Intracellular release of rapamycin from poly (lactic acid) nanospheres modifies autophagy.

    PubMed

    Nagata, Junpei; Matsui, Makoto; Tabata, Yasuhiko

    2016-09-01

    The objective of this study is to investigate the autophagy activity of cells by the intracellular release of rapamycin (Rapa) of an autophagy inducer. Rapa was incorporated into nanospheres of poly (lactic-co-glycolic acid) (PLGA) for the controlled release of Rapa. Rapa was released from the PLGA nanospheres incorporating rapamycin (Rapa-PLGA-NS) with time while the Rapa-PLGA-NS were hydrolytically degraded. When human hepatocellular carcinoma (HepG2) cells were incubated with the Rapa-PLGA-NS, the Rapa-PLGA-NS were internalized, and the intracellular concentration was maintained over four days, indicating the intracellular Rapa release. The microtubule-associated protein 1 light chain (LC3) of an autophagy marker was significantly high for the Rapa-PLGA-NS group compared with the free Rapa group even after four days incubation. In addition, intracellular harmful ubiquitinated proteins were degraded by the intracellular release of Rapa even after four days incubation in contrast to free Rapa. It is concluded that the intracellular Rapa release is effective in modulating the autophagy activity over a longer time period. PMID:27320771

  2. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    SciTech Connect

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-10-02

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  3. The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: effect of additives on drug release rates and mechanical strength.

    PubMed

    Jackson, John; Leung, Fay; Duncan, Clive; Mugabe, Clement; Burt, Helen

    2011-04-01

    Bone cement containing antibiotics is commonly used to treat orthopedic related infections. However, effective treatment (especially of resistant bacteria, methacillin-resistant Staphylococcus aureus (MRSA)) is compromised by very low levels of drug release so that typically less than 10% of loaded drug is released over a 6-week period. The objective of this study was to investigate the effect of incorporation of water soluble excipients (polyethylene glycol, sodium chloride, or dextran) into antibiotic-loaded cement on mechanical strength and drug release properties. Poly(methyl methylacrylate) cement implants containing various amounts of drug (vancomycin, linezolid or fusidic acid (all MRSA active)) and excipients were cast in the form of beads or films and characterized using differential scanning calorimetry. Mechanical strength as assessed by Young's modulus was determined by thermo-mechanical analysis. Drug release was measured by incubation in phosphate buffered saline with analysis by HPLC methods. The inclusion of sodium chloride up to 20% w/w caused only minor reductions in Young's modulus. Vancomycin and linezolid released very slowly from unmodified bone cement beads (less than 3% released by 4 weeks) whereas fusidic acid released more quickly (approximately 8% released by 4 weeks). The inclusion of sodium chloride or dextran in bone cement resulted in major increases in the release rate of vancomycin, linezolid and fusidic acid. These studies support the inclusion of sodium chloride and dextran in bone cement to increase the release rate of vancomycin, linezolid, or fusidic acid without compromising the mechanical strength of the composite material. PMID:25788111

  4. Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

    PubMed

    Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y

    2005-08-01

    Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211

  5. Modulation of leukotriene release from human polymorphonuclear leucocytes by PMA and arachidonic acid.

    PubMed Central

    Raulf, M; König, W

    1988-01-01

    Stimulation of human neutrophils (PMN) with Ca ionophore A23187, opsonized zymosan and formyl-L-methionyl-L-leucyl-phenylalanine (FMLP) led to a time- and dose-dependent release of LTB4, 20-OH-LTB4, 20-COOH-LTB4, 6-trans-LTB4, 12-epi-6-trans LTB4 and LTC4, as detected by reverse-phase HPLC. Preincubation of the PMN suspension in the presence of Ca2+ and Mg2+ with phorbol-12-myristate-13-acetate (PMA) did not release leukotrienes by itself, but modulated the subsequent Ca ionophore-induced leukotriene release. The release of LTC4, 20-OH-LTB4 and 20-COOH-LTB4 was significantly decreased. Lesser effects were observed for the release of LTB4 and the non-enzymatic LTB4 isomers. In contrast, opsonized zymosan and FMLP enhanced the release of LTB4 and LTB4-omega-oxidation products from cells pretreated with PMA. With arachidonic acid as prestimulus, the amounts of the LTB4 isomers (6-trans-LTB4 and 12-epi-6-trans-LTB4) were enhanced significantly on subsequent stimulation with Ca ionophore. Prestimulation of lymphocytes, monocytes and basophilic granulocytes (LMB) with PMA had no significant effects on the ionophore-induced release of LTC4 and LTB4. PMN, but not LMB, suspensions prestimulated with PMA convert exogenously added LTC4 to LTB4 isomers and LTC4 sulphoxide. Our data suggest that preincubation of human granulocytes with PMA modified leukotriene release by activation or inhibition of different metabolic pathways for LTC4 and LTB4. PMID:2838420

  6. Anticancer drug release from poly(N-isopropylacrylamide/itaconic acid) copolymeric hydrogels

    NASA Astrophysics Data System (ADS)

    Taşdelen, B.; Kayaman-Apohan, N.; Güven, O.; Baysal, B. M.

    2005-08-01

    The drug uptake and release of anticancer drug from N-isopropylacrylamide/itaconic acid copolymeric hydrogels containing 0-3 mol% of itaconic acid irradiated at 48 kGy have been investigated. 5-Fluorouracil (5-FU) is used as a model anticancer drug. The effect of 5-FU solution on swelling characteristics of PNIPAAm and P(NIPAAm/IA) copolymeric hydrogels have also been studied. The percent swelling, equilibrium swelling, equilibrium water/5-FU content and diffusion constant values are evaluated for poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide/itaconic) (P(NIPAAm/IA)) hydrogels at 130 ppm of 5-FU solution at room temperature. Diffusion of 5-FU solution into the hydrogels has been found to be the non-Fickian type. Finally, the kinetics of drug release from the hydrogels are examined.

  7. Acid Stimulation (Sour Taste) Elicits GABA and Serotonin Release from Mouse Taste Cells

    PubMed Central

    Huang, Yijen A.; Pereira, Elizabeth; Roper, Stephen D.

    2011-01-01

    Several transmitter candidates including serotonin (5-HT), ATP, and norepinephrine (NE) have been identified in taste buds. Recently, γ-aminobutyric acid (GABA) as well as the associated synthetic enzymes and receptors have also been identified in taste cells. GABA reduces taste-evoked ATP secretion from Receptor cells and is considered to be an inhibitory transmitter in taste buds. However, to date, the identity of GABAergic taste cells and the specific stimulus for GABA release are not well understood. In the present study, we used genetically-engineered Chinese hamster ovary (CHO) cells stably co-expressing GABAB receptors and Gαqo5 proteins to measure GABA release from isolated taste buds. We recorded robust responses from GABA biosensors when they were positioned against taste buds isolated from mouse circumvallate papillae and the buds were depolarized with KCl or a stimulated with an acid (sour) taste. In contrast, a mixture of sweet and bitter taste stimuli did not trigger GABA release. KCl- or acid-evoked GABA secretion from taste buds was Ca2+-dependent; removing Ca2+ from the bathing medium eliminated GABA secretion. Finally, we isolated individual taste cells to identify the origin of GABA secretion. GABA was released only from Presynaptic (Type III) cells and not from Receptor (Type II) cells. Previously, we reported that 5-HT released from Presynaptic cells inhibits taste-evoked ATP secretion. Combined with the recent findings that GABA depresses taste-evoked ATP secretion [1], the present results indicate that GABA and 5-HT are inhibitory transmitters in mouse taste buds and both likely play an important role in modulating taste responses. PMID:22028776

  8. Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

    PubMed

    Castro, D O; Tabary, N; Martel, B; Gandini, A; Belgacem, N; Bras, J

    2016-12-01

    Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with β-cyclodextrin (β-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of β-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with β-CD. The results indicated that β-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached β-CD and a prolonged release was confirmed. In particular, CNC grafted to β-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to β-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy. PMID:27612798

  9. Stimuli responsive charge-switchable lipids: Capture and release of nucleic acids.

    PubMed

    Hersey, Joseph S; LaManna, Caroline M; Lusic, Hrvoje; Grinstaff, Mark W

    2016-03-01

    Stimuli responsive lipids, which enable control over the formation, transformation, and disruption of supramolecular assemblies, are of interest for biosensing, diagnostics, drug delivery, and basic transmembrane protein studies. In particular, spatiotemporal control over a supramolecular structure can be achieved using light activated compounds to induce significant supramolecular rearrangements. As such, a family of cationic lipids are described which undergo a permanent switch in charge upon exposure to 365 nm ultraviolet (UV) light to enable the capture of negatively charged nucleic acids within the self-assembled supramolecular structure of the lipids and subsequent release of these macromolecules upon exposure to UV light and disruption of the assemblies. The lipids are composed of either two different tripeptide head groups, Lysine-Glycine-Glycine (KGG) and Glycine-Glycine-Glycine (GGG) and three different hydrocarbon chain lengths (C6, C10, or C14) terminated by a UV light responsive 1-(2-nitrophenyl)ethanol (NPE) protected carboxylic acid. The photolysis of the NPE protected lipid is measured as a function of time, and the resulting changes in net molecular charge are observed using zeta potential analysis for each head group and chain length combination. A proof of concept study for the capture and release of both linear DNA (calf thymus) and siRNA is presented using an ethidium bromide quenching assay where a balance between binding affinity and supramolecular stability are found to be the key to optimal nucleic acid capture and release. PMID:26896839

  10. Photon-Manipulated Drug Release from Mesoporous Nanocontainer Controlled by Azobenzene-Modified Nucleic Acid

    PubMed Central

    Yuan, Quan; Zhang, Yunfei; Chen, Tao; Lu, Danqing; Zhao, Zilong; Zhang, Xiaobing; Li, Zhenxing; Yan, Chun-Hua; Tan, Weihong

    2012-01-01

    Herein a photon manipulated mesoporous release system was constructed based on azobenzene-modified nucleic acids. In this system, the azobenzene-incorporated DNA double strands were immobilized at the pore mouth of meso-porous silica nanoparticles. The photo-isomerization of azobenzene induced dehybridization/hybridization switch of complementary DNA, causing uncapping/capping of pore gates of mesoporous silica. This nanoplatform permits holding of guest molecules within the nanopores under visible light but release them when light wavelength turns to UV range. These DNA/mesoporous silica hybrid nanostructures were exploited as carriers for cancer cell chemotherapy drug doxorubicin (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is light wavelength sensitive. Switching of the light from visible to UV range uncapped the pores causes the release of DOX from the mesoporous silica nanospheres and an obvious cytotoxic effect on cancer cells. We envision that this photo-controlled drug release system could find potential applications in cancer therapy. PMID:22670595

  11. Effects of processing on the release profiles of matrix systems containing 5-aminosalicylic acid.

    PubMed

    Korbely, Anita; Kelemen, András; Kása, Péter; Pintye-Hódi, Klára

    2012-12-01

    The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6-19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0-13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54-56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer-Peppas model or the Hopfenberg model. PMID:23054987

  12. Release of arachidonic acid from oligodendrocytes by terminal complement proteins, C5b-C9

    SciTech Connect

    Shirazi, Y.; Imagawa, D.K.; Shin, M.L.

    1986-03-01

    Activation of C5b-C9 on monocytes, macrophages, platelets and neutrophils induces membrane lipid hydrolysis and generates arachidonic acid (AA) and its oxygenated derivatives. Additionally, activation of C5b-C9 and myelin lipid hydrolysis has been observed in demyelination. The authors have investigated the modulatory effect of C5b-9 on membrane lipid hydrolysis of oligodendrocytes (OLG), the myelin producing cells in the central nervous system. Antibody-sensitized rat OLG, prelabeled with /sup 14/C AA were treated with excess C6-deficient rabbit serum reconstituted with limiting doses of C6. Qualitative analysis of the supernatants by HPLC revealed the presence of both cyclooxygenase and lipooxygenase products. Prostaglandin E/sub 2/, leukotriene (LT) E/sub 4/, LTB/sub 4/ and free AA were the major radiolabeled products. The kinetics and dose response of LTB/sub 4/ release with respect to the cytolytic dose of C5b-9 were quantitated by radioimmunoassay. LTB/sub 4/ release approached maximum in 1 hr and higher amounts were detected with fewer C5b-9 channels. Addition of C8 to OLG bearing C5b-7 intermediates induced maximum LTB/sub 4/ release without further enhancement by C9 in contrast to the absolute requirement of C9 in mediator release from rat neutrophils. Thus, the requirement of C5b-8 or C5b-9 in mediator release appears to be cell-type dependent.

  13. An evaluation of trace element release associated with acid mine drainage

    NASA Astrophysics Data System (ADS)

    Sullivan, Patrick J.; Yelton, Jennifer L.

    1988-12-01

    The determination of trace element release from geologic materials, such as oil shale and coal overburden, is important for proper solid waste management planning. The objective of this study was to determine a correlation between trace element residency and concentration to trace element release using the following methods: (1) sequential selective dissolution for determining trace element residencies, (2) toxicity characteristic leaching procedure (TCLP), and (3) humidity cell weathering study simulating maximum trace element release. Two eastern oil shales were used, a New albany shale that contains 4.6 percent pyrite, and a Chattanooga shale that contains 1.5 percent pyrite. Each shale was analyzed for elemental concentrations by soluble, adsorbed, organic, carbonate, and sulfide phases. All leachates were analyzed to determine total trace element concentrations. The results of the selective dissolution studies show that each trace element has a unique distribution between the various phases. Thus, it is possible to predict trace element release based on trace element residency. The TCLP results show that this method is suitable for assessing soluble trace element release but does not realistically assess potential hazards. The results of the humidity cell studies do demonstrate a more reasonable method for predicting trace element release and potential water quality hazards. The humidity cell methods, however, require months to obtain the required data with a large number of analytical measurements. When the selective dissolution data are compared to the trace element concentrations in the TCLP and humidity cell leachates, it is shown that leachate concentrations are predicted by the selective dissolution data. Therefore, selective dissolution may represent a rapid method to assess trace element release associated with acid mine drainage.

  14. Influence of admixed citric acid on the release profile of pelanserin hydrochloride from HPMC matrix tablets.

    PubMed

    Espinoza, R; Hong, E; Villafuerte, L

    2000-05-25

    Pelanserin is a weakly basic experimental drug with a short half-life and a prolonged release formulation was developed using hydroxypropyl methylcellulose (HPMC) and citric acid to set up a system bringing about gradual release of this drug. For this purpose powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using 900 ml HCl 0.1 N, the first 3 h, and phosphate buffer pH 7.4, h 3-8. Dissolution curves were described by M(t)/M(inf)=kt(n), applied separately for each dissolution medium. The dissolution mechanism involved a coupled diffusion/relaxation with a trend favoring the diffusion mechanism with increasing citric acid concentrations. Increasing concentrations of citric acid produced increasing values of the kinetic constants, in a cubic relationship. Higher HPMC proportions produced slower dissolution rates but with a citric acid compensating more clearly a decreased solubility of pelanserin at pH 7.4. Individually calculated dissolution curves showed experimental 8 h pelanserin dissolution in a range of 65-99% for matrices with 100 mg HPMC/tab., while those with 200 mg HPMC/tab. were in the range 57-73%. PMID:10878323

  15. Arachidonate metabolism, 5-hydroxytryptamine release and aggregation in human platelets activated by palmitaldehyde acetal phosphatidic acid.

    PubMed Central

    Brammer, J. P.; Maguire, M. H.

    1984-01-01

    Palmitaldehyde acetal phosphatidic acid ( PGAP ) caused dose-dependent aggregation of human platelets resuspended in modified Tyrode medium, with a threshold concentration of 0.5-1 microM and an EC50 of 4 microM. Concentrations of PGAP which elicited biphasic irreversible aggregation concomitantly induced formation of 1.02 +/- 0.029 nmol (mean +/- s.e. mean) of malondialdehyde (MDA) per 10(9) platelets and caused release of 58 +/- 2.8% of platelet [14C]-5-hydroxytryptamine ([14C]-5-HT) from prelabelled platelets; no MDA formation or [14C]-5-HT release occurred at lower doses of PGAP which elicited only monophasic reversible aggregation. Adenosine 5'-pyrophosphate (ADP)-induced platelet activation resulted in formation of 0.344 +/- 0.004 nmol of MDA per 10(9) platelets in association with irreversible aggregation and 49.1 +/- 1% release of [14C]-5-HT. Mepacrine, a phospholipase A2 inhibitor, at 2.5 microM reduced PGAP -induced MDA formation and [14C]-5-HT release by the resuspended platelets without affecting irreversible aggregation; higher concentrations of mepacrine abolished all three responses. Chlorpromazine, a calmodulin antagonist, similarly inhibited PGAP -induced MDA formation and irreversible aggregation, and at 100 microM abolished monophasic aggregation. The cyclo-oxygenase inhibitor indomethacin caused a concentration-dependent reduction of PGAP -induced MDA formation by resuspended human platelets without significantly inhibiting [14C]-5-HT release or irreversible aggregation; concentrations (greater than or equal to 1.75 microM) which inhibited MDA formation by more than 94% abolished [14C]-5-HT release, and converted second phase irreversible aggregation to an extensive reversible response. 2-Methylthioadenosine 5'-phosphate (2 methylthio-AMP), an ADP antagonist, inhibited PGAP -induced MDA formation, [14C]-5-HT release and second phase aggregation in the human platelet suspensions in a parallel, concentration-dependent manner; at 9.4 microM 2

  16. The alpha 1-adrenergic transduction system in hamster brown adipocytes. Release of arachidonic acid accompanies activation of phospholipase C.

    PubMed Central

    Schimmel, R J

    1988-01-01

    Previous studies of brown adipocytes identified an increased breakdown of phosphoinositides after selective alpha 1-adrenergic-receptor activation. The present paper reports that this response, elicited with phenylephrine in the presence of propranolol and measured as the accumulation of [3H]inositol phosphates, is accompanied by increased release of [3H]arachidonic acid from cells prelabelled with [3H]arachidonic acid. Differences between stimulated arachidonic acid release and formation of inositol phosphates included a requirement for extracellular Ca2+ for stimulated release of arachidonic acid but not for the formation of inositol phosphates and the preferential inhibition of inositol phosphate formation by phorbol 12-myristate 13-acetate. The release of arachidonic acid in response to phenylephrine was associated with an accumulation of [3H]arachidonic acid-labelled diacylglycerol, and this response was not dependent on extracellular Ca2+ but was partially prevented by treatment with the phorbol ester. The release of arachidonic acid was also stimulated by melittin, which increases the activity of phospholipase A2, by ionophore A23187, by lipolytic stimulation with forskolin and by exogenous phospholipase C. The arachidonic acid response to phospholipase C was completely blocked by RHC 80267, an inhibitor of diacylglycerol lipase, but this inhibitor had no effect on release stimulated with melittin or A23187 and inhibited phenylephrine-stimulated release by only 40%. The arachidonate response to forskolin was additive with the responses to either phenylephrine or exogenous phospholipase C. These data indicate that brown adipocytes are capable of releasing arachidonic acid from neutral lipids via triacylglycerol lipolysis, and from phospholipids via phospholipase A2 or by the sequential activities of phospholipase C and diacylglycerol lipase. Our findings also suggest that the action of phenylephrine to promote the liberation of arachidonic acid utilizes both

  17. Selectively crosslinked hyaluronic acid hydrogels for sustained release formulation of erythropoietin.

    PubMed

    Motokawa, Keiko; Hahn, Sei Kwang; Nakamura, Teruo; Miyamoto, Hajime; Shimoboji, Tsuyoshi

    2006-09-01

    A novel sustained release formulation of erythropoietin (EPO) was developed using hyaluronic acid (HA) hydrogels. For the preparation of HA hydrogels, adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and analyzed with (1)H NMR. The degree of HA-ADH modification was about 69%. EPO was in situ encapsulated into HA-ADH hydrogels through a selective cross-linking reaction of bis(sulfosuccinimidyl) suberate (BS(3)) to hydrazide group (pK(a) = 3.0) of HA-ADH rather than to amine group (pK(a) > 9) of EPO. The denaturation of EPO during HA-ADH hydrogel synthesis was drastically reduced with decreasing pH from 7.4 to 4.8. The specific reactivity of BS(3) to hydrazide at pH = 4.8 might be due to its low pK(a) compared with that of amine. In vitro release of EPO in phosphate buffered saline at 37 degrees C showed that EPO was released rapidly for 2 days and then slowly up to 4 days from HA-ADH hydrogels. When the hydrogels were dried at 37 degrees C for a day, however, longer release of EPO up to 3 weeks could be demonstrated. According to in vivo release test of EPO from HA-ADH hydrogels in SD rats, elevated EPO concentration higher than 0.1 ng/mL could be maintained from 7 days up to 18 days depending on the preparation methods of HA-ADH hydrogels. There was no adverse effect during and after HA-ADH hydrogel implantation. PMID:16721757

  18. Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase.

    PubMed

    Sahonero-Canavesi, Diana X; Sohlenkamp, Christian; Sandoval-Calderón, Mario; Lamsa, Anne; Pogliano, Kit; López-Lara, Isabel M; Geiger, Otto

    2015-09-01

    Phospholipids are well known for their membrane-forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth. PMID:25711932

  19. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release

    PubMed Central

    Chu, David S.H.; Johnson, Russell N.; Pun, Suzie H.

    2011-01-01

    Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK10, containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(l)-lysine for nucleic acid binding, (ii) pHCath(d)K10, containing the FKFL linker with oligo-(d)-lysine, and (iii) pH(d)Cath(d)K10, containing all (d) amino acids. Cathepsin B degraded copolymers pHCathK10 and pHCath(d)K10 within one hour while no degradation of pH(d)Cath(d)K10 was observed. Polyplexes formed with pHCathK10 copolymers show DNA release by 4 hrs of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(d)K10 and pH(d)Cath(d)K10 show no DNA release within 8 hrs. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK10 was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. PMID:22036879

  20. Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells.

    PubMed

    Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E; Ziegler, Mathias; Nikiforov, Andrey

    2015-11-01

    NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. PMID:26385918

  1. Release of nitrous acid and nitrogen dioxide from nitrate photolysis in acidic aqueous solutions.

    PubMed

    Scharko, Nicole K; Berke, Andrew E; Raff, Jonathan D

    2014-10-21

    Nitrate (NO3(-)) is an abundant component of aerosols, boundary layer surface films, and surface water. Photolysis of NO3(-) leads to NO2 and HONO, both of which play important roles in tropospheric ozone and OH production. Field and laboratory studies suggest that NO3¯ photochemistry is a more important source of HONO than once thought, although a mechanistic understanding of the variables controlling this process is lacking. We present results of cavity-enhanced absorption spectroscopy measurements of NO2 and HONO emitted during photodegradation of aqueous NO3(-) under acidic conditions. Nitrous acid is formed in higher quantities at pH 2-4 than expected based on consideration of primary photochemical channels alone. Both experimental and modeled results indicate that the additional HONO is not due to enhanced NO3(-) absorption cross sections or effective quantum yields, but rather to secondary reactions of NO2 in solution. We find that NO2 is more efficiently hydrolyzed in solution when it is generated in situ during NO3(-) photolysis than for the heterogeneous system where mass transfer of gaseous NO2 into bulk solution is prohibitively slow. The presence of nonchromophoric OH scavengers that are naturally present in the environment increases HONO production 4-fold, and therefore play an important role in enhancing daytime HONO formation from NO3(-) photochemistry. PMID:25271384

  2. Controlled release of tyrosol and ferulic acid encapsulated in chitosan-gelatin films after electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Benbettaïeb, Nasreddine; Assifaoui, Ali; Karbowiak, Thomas; Debeaufort, Frédéric; Chambin, Odile

    2016-01-01

    This work deals with the study of the release kinetics of antioxidants (ferulic acid and tyrosol) incorporated into chitosan-gelatin edible films after irradiation processes. The aim was to determine the influence of electron beam irradiation (at 60 kGy) on the retention of antioxidants in the film, their release in water (pH=7) at 25 °C, in relation with the barrier and mechanical properties of biopolymer films. The film preparation process coupled to the irradiation induced a loss of about 20% of tyrosol but did not affect the ferulic acid content. However, 27% of the ferulic acid remained entrapped in the biopolymer network during the release experiments whereas all tyrosol was released. Irradiation induced a reduction of the release rate for both compounds, revealing that cross-linking occurred during irradiation. This was confirmed by the mechanical properties enhancement which tensile strength value significantly increased and by the reduction of permeabilities. Although molecular weights, molar volume and molecular radius of the two compounds are very similar, the effective diffusivity of tyrosol was 40 times greater than that of ferulic acid. The much lower effective diffusion coefficient of ferulic acid as determined from the release kinetics was explained by the interactions settled between ferulic acid molecules and the gelatin-chitosan matrix. As expected, the electron beam irradiation allowed modulating the retention and then the release of antioxidants encapsulated.

  3. Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants.

    PubMed

    Zhang, Feng; Meng, Fan; Lubach, Joseph; Koleng, Joseph; Watson, N A

    2016-08-01

    The interactions between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) in aqueous medium at pH 6.8 were investigated in the current study. We have also studied the effect of interpolymer interactions and various formulation variables, including the molecular weight of PEO, the ratio between PEO and PAA, the crystallinity of PEO, and the presence of an acidifying agent, on the release of theophylline from matrix tablets containing both PEO and PAA as release retardants. At pH 6.8, the synergy in solution viscosity between PEO and PAA as the result of ion-dipole interaction was observed in this study. The release of theophylline from the matrix tablets containing physical mixtures of PEO and PAA was found to be a function of dissolution medium pH because of the pH-dependent interactions between these two polymers. Because of the formation of water insoluble interpolymer complex between PEO and PAA in aqueous medium at pH below 4.0, the release of theophylline was independent of PEO molecular weight and was controlled by Fickian diffusion mechanism in 0.01N hydrochloric acid solution. In comparison, the drug release was a function of PEO molecular weight and followed the anomalous transport mechanism in phosphate buffer pH 6.8. The presence of PAA exerted opposite effects on the release of theophylline in phosphate buffer pH 6.8. In one aspect, theophylline release was accelerated because the erosion of PAA was much faster than that of PEO at pH6.8. On the opposite aspect, theophylline release was slowed down because of the formation of insoluble complex inside the gel layer as the result of the acidic microenvironment induced by PAA, and the increase in the viscosity of the gel layer as the result of the synergy between PEO and PAA. These two opposite effects offset each other. As a result, the release of theophylline remained statistically the same even when 75% PEO in the formulation was replaced with PAA. In phosphate buffer pH 6.8, the release of

  4. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols

    PubMed Central

    Bomar, Lindsey; Brugger, Silvio D.; Yost, Brian H.; Davies, Sean S.

    2016-01-01

    ABSTRACT Bacterial interspecies interactions play clinically important roles in shaping microbial community composition. We observed that Corynebacterium spp. are overrepresented in children free of Streptococcus pneumoniae (pneumococcus), a common pediatric nasal colonizer and an important infectious agent. Corynebacterium accolens, a benign lipid-requiring species, inhibits pneumococcal growth during in vitro cocultivation on medium supplemented with human skin surface triacylglycerols (TAGs) that are likely present in the nostrils. This inhibition depends on LipS1, a TAG lipase necessary for C. accolens growth on TAGs such as triolein. We determined that C. accolens hydrolysis of triolein releases oleic acid, which inhibits pneumococcus, as do other free fatty acids (FFAs) that might be released by LipS1 from human skin surface TAGs. Our results support a model in which C. accolens hydrolyzes skin surface TAGS in vivo releasing antipneumococcal FFAs. These data indicate that C. accolens may play a beneficial role in sculpting the human microbiome. PMID:26733066

  5. Controlled release of anti-diabetic drug Gliclazide from poly(caprolactone)/poly(acrylic acid) hydrogels.

    PubMed

    Bajpai, S K; Chand, Navin; Soni, Shweta

    2015-01-01

    Drug Gliclazide (Glz) has limited solubility and low bioavailability. In order to obtain a controlled release of this drug and to improve its bioavailability, the drug has been loaded into poly(caprolactone) (PCL)/poly(acrylic acid) (PAAc) hydrogels, prepared by free radical polymerization of acrylic acid in the presence of poly(caprolactone) in acetone medium using azo-isobutyronitrile as initiator and N,N' methylene bisacrylamide as cross-linking agent. The swelling behaviour of these hydrogels has been investigated in the physiological gastric and intestinal fluids to obtain an optimum composition suitable for delivery of a biologically active compound. The gels were loaded with anti-diabetic drug Glz and a detailed investigation of release of drug has been carried out. Various kinetic models have been applied on the release data. Finally, the Albino wistar rats were treated for Streptozotocin plus nicotinamide - induced diabetes using a Glz-loaded PCL/PAAc hydrogel. The results indicated a fair reduction in the glucose level of rats. PMID:26135033

  6. The cysteine releasing pattern of some antioxidant thiazolidine-4-carboxylic acids.

    PubMed

    Önen Bayram, F Esra; Sipahi, Hande; Acar, Ebru Türköz; Kahveci Ulugöl, Reyhan; Buran, Kerem; Akgün, Hülya

    2016-05-23

    Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures' antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself. PMID:27017266

  7. Effect of lactobionic acid on the acidification, rheological properties and aroma release of dairy gels.

    PubMed

    Ribeiro, Jéssica C Bigaski; Granato, Daniel; Masson, Maria Lucia; Andriot, Isabelle; Mosca, Ana Carolina; Salles, Christian; Guichard, Elisabeth

    2016-09-15

    The food industry is investigating new technological applications of lactobionic acid (LBA). In the current work, the effect of lactobionic acid on the acidification of dairy gels (pH 5.5 and 6.2), rheological properties using a double compression test, sodium mobility using (23)Na NMR technique and aroma release using headspace GC-FID were studied. Our results showed that it is possible to use LBA as an alternative to glucono-δ-lactone (GDL) for the production of dairy gels with a controlled pH value. Small differences in the rheological properties and in the amount of aroma volatile organic compounds that were released in the vapour phase, but no significant difference in the sodium ion mobility were obtained. The gels produced with LBA were less firm and released less volatile aroma compounds than the gels produced with GDL. The gels at pH 6.2 were firmer than those at pH 5.5 and had a more organised structure around the sodium ions. PMID:27080885

  8. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  9. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  10. A selective defect in arachidonic acid release from macrophage membranes in high potassium media.

    PubMed

    Aderem, A A; Scott, W A; Cohn, Z A

    1984-10-01

    Murine peritoneal macrophages cultured in minimal essential medium (alpha-MEM; 118 mM Na+, 5 mM K+) released arachidonic acid (20:4) from phospholipids on encountering a phagocytic stimulus of unopsonized zymosan. In high concentrations of extracellular K+ (118 mM), 3H release from cells prelabeled with [3H]20:4 was inhibited 80% with minimal reduction (18%) in phagocytosis. The inhibitory effect of K+ on 20:4 release was fully reversed on returning cells to medium containing Na+ (118 mM). Preingestion of zymosan particles by macrophages maintained in high K+ medium resulted in cells being "primed" for 20:4 release, which was only effected (without the further addition of particles) by changing the medium to one containing Na+. In contrast, 20:4 release from cells stimulated with the calcium ionophore A23187 was unimpaired by the elevated K+ medium, suggesting no direct effect of high K+ on the phospholipase. Macrophages stimulated with zymosan in alpha-MEM metabolized the released 20:4 to prostacyclin, prostaglandin E2 (PGE2), and leukotriene C (LTC). The smaller quantity of released 20:4 in high K+ medium was recovered as 6-Keto-PGF1 alpha, the breakdown product of prostacyclin, and PGE2. No LTC was synthesized. In high K+, resting (no zymosan) macrophages synthesized hydroxyeicosatetraenoic acids from exogeneously supplied 20:4 in proportions similar to cells maintained in alpha-MEM. These findings and the similarity of products (including LTC) produced by A23187 stimulated cells in alpha-MEM and high K+ medium indicated that the cyclooxygenase and lipoxygenase pathway enzymes were not directly inhibited by high extracellular K+. We conclude that high concentrations of extracellular K+ uncouple phagocytosis of unopsonized zymosan from the induction of the phospholipase responsible for the 20:4 cascade and suggest that the lesion is at the level of signal transduction between the receptor-ligand complex and the phospholipase. PMID:6434547

  11. Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere.

    PubMed

    Pan, Fujing; Liang, Yueming; Zhang, Wei; Zhao, Jie; Wang, Kelin

    2016-01-01

    In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and β-1,4-N-acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID:27252713

  12. Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere

    PubMed Central

    Pan, Fujing; Liang, Yueming; Zhang, Wei; Zhao, Jie; Wang, Kelin

    2016-01-01

    In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and β-1,4-N-acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID:27252713

  13. 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.

  14. Release properties of tannic acid from hydrogen bond driven antioxidative cellulose nanofibrous films.

    PubMed

    Zhou, Bin; Hu, Xiaoqian; Zhu, Jinjin; Wang, Zhenzhen; Wang, Xichang; Wang, Mingfu

    2016-10-01

    Layer-by-layer (LBL) assembled films have been exploited for surface-mediated bioactive compound delivery. Here, an antioxidative hydrogen-bonded multilayer electrospun nanofibrous film was fabricated from tannic acid (TA), acting as a polyphenolic antioxidant, and poly(ethylene glycol) (PEG) via layer-by-layer assembly. It overcame the burst release behavior of nanofibrous carrier, due to the reversible/dynamic nature of hydrogen bond, which was responded to external stimuli. The PEG/TA nanofibrous films disassembled gradually and released TA to the media, when soaked in aqueous solutions. The release rate of TA increased with increasing bilayer number, pH and temperature, but decreased with enhancing ionic strength. The surface morphology of the nanofibrous mats was observed by scanning electron microscopy (SEM). The following antioxidant activity assay revealed that it could scavenge DPPH free radicals and ABTS(+) cation radicals, a major biological activity of polyphenols. This technology can be used to fabricate other phenolic-containing slowly releasing antioxidative nanofibrous films. PMID:27234492

  15. Study of the release of a microencapsulated acid dye in polyamide dyeing using mixed cationic liposomes.

    PubMed

    de Sousa, Isabel S C; Castanheira, Elisabete M S; Rocha Gomes, Jaime I N; Real Oliveira, M Elisabete C D

    2011-06-01

    The main objective of this work was to increase the retarding effect of the acid dye Telon(®) Blue RR (C.I. Acid Blue 62; DyStar, Frankfurt, Germany) release on polyamide fibres dyeing by encapsulation of the dye in liposomes as an alternative to synthetic auxiliaries, in order to reduce effluent pollution. The retarding effect achieved with the use of mixed cationic liposomes of dioctadecyldimethylammonium bromide (DODAB)/soybean lecithin (containing a 10% molar fraction of DODAB) was better in comparison with either pure soybean lecithin liposomes or synthetic auxiliaries. The retarding effect of liposomes on the dye release was analysed through changes in the absorption and fluorescence spectra of the acid dye at different conditions. The effect of temperature (in the range of 25 °C - 70 °C) on the spectroscopic behaviour of the dye in the absence and in presence of polyamide was also studied, in order to simulate the dyeing conditions. Exhaustion curves obtained in dyeing experiments showed that, below 45 °C, the retarding effect of the mixed liposomes (lecithin/DODAB (9:1)) was similar to that of the auxiliaries, but better than the one of pure lecithin liposomes. At higher temperatures (above 45 °C), the system lecithin/DODAB presents a better performance, achieving a higher final exhaustion level when compared with the commercial leveling agent without losing the smoothing effect of lecithin. PMID:20550462

  16. Novel fatty acid gentamicin salts as slow-release drug carrier systems for anti-infective protection of vascular biomaterials.

    PubMed

    Obermeier, A; Matl, F D; Schwabe, J; Zimmermann, A; Kühn, K D; Lakemeier, S; von Eisenhart-Rothe, R; Stemberger, A; Burgkart, R

    2012-07-01

    Infections of vascular prostheses are still a major risk in surgery. The current work presents an in vitro evaluation of novel slow release antibiotic coatings based on new gentamicin fatty acid salts for polytetrafluoroethylene grafts. These grafts were coated with gentamicin sodium dodecyl sulfate, gentamicin laurate and gentamicin palmitate. Drug release kinetics, anti-infective characteristics, biocompatibility and haemocompatibility of developed coatings were compared to commercially available gelatin sealed PTFE grafts (SEALPTFE™) and knitted silver coated Dacron(®) grafts (InterGard(®)). Each gentamicin fatty acid coating showed a continuous drug release in the first eight hours followed by a low continuous release. Grafts coated with gentamicin fatty acids reduced bacterial growth even beyond pathologically relevant high concentrations. Cytotoxicity levels depending on drug formulation bringing up gentamicin palmitate as the most promising biocompatible coating. Thrombelastography studies, ELISA assays and an amidolytic substrate assay confirmed haemocompatibility of developed gentamicin fatty acid coatings comparable to commercially available grafts. PMID:22476651

  17. Facile method to prepare silk fibroin/hyaluronic acid films for vascular endothelial growth factor release.

    PubMed

    Zhou, Juan; Zhang, Bin; Liu, Xunwei; Shi, Lijun; Zhu, Jun; Wei, Daixu; Zhong, Jian; Sun, Gang; He, Dannong

    2016-06-01

    A facile approach was proposed to prepare silk fibroin (SF) and hyaluronic acid (HA) composite films from aqueous solution without crosslinking or any post treatment. Only by controlling the HA content and film formation temperature during the film casting, the HA/SF films with different composition were prepared. The films were then characterized by structural characteristics, thermal stability, morphology, water stability, water absorption, mechanical properties. After immersing in water for 24h, all of the films showed good structural integrity. The degradation rate of the HA/SF films in protease XIV can be controlled by changing the film formation temperature and HA content. Decreasing the temperature and adding HA resulted in the rapid release of VEGF (vascular endothelial growth factor) from the HA/SF films. Overall, the 5% HA/SF films formed at 37°C with more rapid VEGF release exhibited great potential in drug delivery, especially when the rapid vascularization was needed. PMID:27083373

  18. Controlled release of acetylsalicylic acid from polythiophene/carrageenan hydrogel via electrical stimulation.

    PubMed

    Pairatwachapun, Sanita; Paradee, Nophawan; Sirivat, Anuvat

    2016-02-10

    Blends between polythiophene (PTh) and a carrageenan hydrogel were fabricated as the matrix for the electric field assisted drug release. The pristine carrageenan and the blend films were prepared by the solution casting using acetylsalicylic acid (ASA) as the anionic model drug and Mg(2+), Ca(2+), and Ba(2+) as the crosslinking agents. The ASA was released by the Fickian diffusion mechanism. The diffusion coefficient decreased with increasing crosslinking ratio or decreasing crosslinking ionic radii. The diffusion coefficients were greater with the applied electrical potentials by an order of magnitude relative to those without electric field. Moreover, the diffusion coefficients with PTh as the drug carrier were higher than those without PTh. Thus, the presence of the conductive polymer in the hydrogel blend coupled with applied electric field is shown here to drastically enhance the drug delivery rate. PMID:26686123

  19. Acid neutralization mechanisms and metal release in mine tailings: a laboratory column experiment

    NASA Astrophysics Data System (ADS)

    Jurjovec, Jasna; Ptacek, Carol J.; Blowes, David W.

    2002-05-01

    Mining and milling of base metal ore deposits can result in the release of metals to the environment. When sulfide minerals contained in mine tailings are exposed to oxygen and water, they oxidize and dissolve. Two principal antagonistic geochemical processes affect the migration of dissolved metals in tailings impoundments: sulfide oxidation and acid neutralization. This study focuses on acid neutralization reactions occurring in the saturated zone of tailings impoundments. To simulate conditions prevailing in many tailings impoundments, 0.1 mol/L sulfuric acid was passed continuously through columns containing fresh, unoxidized tailings, collected at Kidd Creek metallurgical site. The results of this column experiment represent a detailed temporal observation of pH, Eh, and metal concentrations. The results are consistent with previous field observations, which suggest that a series of mineral dissolution-precipitation reactions control pH and metal mobility. Typically, the series consists of carbonate minerals, Al and Fe(III) hydroxides, and aluminosilicates. In the case of Kidd Creek tailings, the dissolution series consists of ankerite-dolomite, siderite, gibbsite, and aluminosilicates. In the column experiment, three distinct pH plateaus were observed: 5.7, 4.0, and 1.3. The releases of trace elements such as Cd, Co, Cr, Cu, Li, Ni, Pb, V, and Zn were observed to be related to the pH buffering zones. High concentrations of Zn, Ni, and Co were observed at the first pH plateau (pH 5.7), whereas Cd, Cr, Pb, As, V, and Al were released as the pH of the pore water decreased to 4.0 or less.

  20. Single-crystalline ceramic whisker-reinforced carboxylic acid-resin composites with fluoride release.

    PubMed

    Xu, H H; Eichmiller, F C; Antonucci, J M; Flaim, G M

    2000-01-01

    Currently available glass-ionomer, resin-modified glass-ionomer, and compomer materials have relatively low strength and toughness and, therefore, are inadequate for use in large stress-bearing posterior restorations. In the present study, ceramic single-crystalline whiskers were mixed with fluorosilicate glass particles and used as fillers to reinforce experimental carboxylic acid-resin composites. The carboxylic acid was a monofunctional methacryloxyethyl phthalate (MEP). Five mass fractions of whisker/(whisker + fluorosilicate glass), and corresponding resin (resin + MEP), were evaluated. Four control materials were also tested for comparison: a glass ionomer, a resin-modified glass ionomer, a compomer, and a hybrid composite resin. Flexural specimens were fabricated to measure the flexural strength, elastic modulus, and work-of-fracture (an indication of toughness). Fluoride release was measured by using a fluoride ion selective electrode. The properties of whisker composites depended on the whisker/(whisker + fluorosilicate glass) mass fraction. At a mass fraction of 0.8, the whisker composite had a flexural strength in MPa (mean +/- sd; n = 6) of 150 +/- 16, significantly higher than that of a glass ionomer (15 +/- 7) or a compomer control (89 +/- 18) (Tukey's multiple comparison test; family confidence coefficient = 0.95). Depending on the ratio of whisker:fluorosilicate glass, the whisker composites had a cumulative fluoride release up to 60% of that of a traditional glass ionomer. To conclude, combining ceramic whiskers and fluorosilicate glass in a carboxylic acid-resin matrix can result in fluoride-releasing composites with significantly improved mechanical properties. PMID:11203805

  1. p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts

    PubMed Central

    Seok, Jin Kyung

    2015-01-01

    Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging. PMID:25954129

  2. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE

    PubMed Central

    Morawin, B.; Turowski, D.; Naczk, M.; Siatkowski, I.

    2014-01-01

    The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient). It significantly increased serum concentrations of nitric oxide (NO), hydrogen peroxide (H2O2) and pro-oxidative products such as 8-isoprostanes (8-iso), lipid peroxides (LPO) and protein carbonyls (PC). α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise) resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r = 0.718, P < 0.01). Serum total creatine kinase (CK) activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L-1, α-lipoic acid 481 ± 103 IU · L-1), and correlated with EPO (r = 0.478, P < 0.01) in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise. PMID:25177095

  3. Influence of fatty acid oxidation rate on glycerol release from cardiac myocytes

    SciTech Connect

    Larsen, T.S.; Severson, D.L.

    1986-03-05

    Quiescent cardiac myocytes are characterized by low rates of fatty acid oxidation due to the reduced energy demand compared with beating hearts. The accumulation of intracellular fatty acid metabolites may, therefore, result in feed-back inhibition of the cardiac lipase responsible for the mobilization of triacylglycerols (lipolysis). The objective of this study was to examine if interventions that increase fatty acid oxidation rates in myocytes have an effect on lipolysis. Addition of 100 ..mu..M dinitrophenol (DNP) to calcium-tolerant rat ventricular myocytes caused an increase in the rate of /sup 14/C-oleic acid oxidation from 1.11 +/- 0.06 to 2.38 +/- 0.17 nmol /sup 14/CO/sub 2//10/sup 6/ cells/min (115% stimulation; mean +/- S.D., n = 3). In parallel incubations, DNP increased the rate of lipolysis from 4.4 +/- 1.7 to 13.6 +/- 3.2 nmol glycerol/10/sup 6/ cells/30 min (215% stimulation). The addition of 1 mM barium to a modified Ringer's incubation medium produced an increase in the contractile activity of the myocytes, and increased the rates of oleic acid oxidation from 0.62 +/- 0.16 to 0.88 +/- 0.23 nmol/10/sup 6/ cells/min (42% stimulation; n = 6) and lipolysis from 13.1 +/- 6.5 to 22.2 +/- 6.4 nmol/10/sup 6/ cells/30 min (70% stimulation). These data show that stimulation of fatty acid oxidation in myocardial myocytes is accompanied by increased lipolytic rates, the latter probably due to release of feed-back inhibition of cardiac lipases by accumulated fatty acid metabolites.

  4. Performance of optimized noncanonical amino acid mutagenesis systems in the absence of release factor 1.

    PubMed

    Zheng, Yunan; Lajoie, Marc J; Italia, James S; Chin, Melissa A; Church, George M; Chatterjee, Abhishek

    2016-05-24

    Site-specific incorporation of noncanonical amino acids (ncAAs) into proteins expressed in E. coli using UAG-suppression competes with termination mediated by release factor 1 (RF1). Recently, unconditional deletion of RF1 was achieved in a genomically recoded E. coli (C321), devoid of all endogenous UAG stop codons. Here we evaluate the efficiency of ncAA incorporation in this strain using optimized suppression vectors. Even though the absence of RF1 does not benefit the suppression efficiency of a single UAG codon, multi-site incorporation of a series of chemically distinct ncAAs was significantly improved. PMID:27027374

  5. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    PubMed Central

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2006-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Gαi, Gαq and Gα12/13 signaling pathways, and a PKCα inhibitor, Gö6976 blocked potentiation while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a non-selective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the N-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus, PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  6. Ferulic acid release and 4-vinylguaiacol formation during brewing and fermentation: indications for feruloyl esterase activity in Saccharomyces cerevisiae.

    PubMed

    Coghe, Stefan; Benoot, Koen; Delvaux, Filip; Vanderhaegen, Bart; Delvaux, Freddy R

    2004-02-11

    The release of ferulic acid and the subsequent thermal or enzymatic decarboxylation to 4-vinylguaiacol are inherent to the beer production process. Phenolic, medicinal, or clove-like flavors originating from 4-vinylguaiacol frequently occur in beer made with wheat or wheat malt. To evaluate the release of ferulic acid and the transformation to 4-vinylguaiacol, beer was brewed with different proportions of barley malt, wheat, and wheat malt. Ferulic acid as well as 4-vinylguaiacol levels were determined by HPLC at several stages of the beer production process. During brewing, ferulic acid was released at the initial mashing phase, whereas moderate levels of 4-vinylguaiacol were formed by wort boiling. Higher levels of the phenolic flavor compound were produced during fermentations with brewery yeast strains of the Pof(+) phenotype. In beer made with barley malt, ferulic acid was mainly released during the brewing process. Conversely, 60-90% of ferulic acid in wheat or wheat malt beer was hydrolyzed during fermentation, causing higher 4-vinylguaiacol levels in these beers. As cereal enzymes are most likely inactivated during wort boiling, the additional release of ferulic acid during fermentation suggests the activity of feruloyl esterases produced by brewer's yeast. PMID:14759156

  7. Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials.

    PubMed

    Faucher, Keith M; Artzi, Natalie; Beck, Moshe; Beckerman, Rita; Moodie, Geoff; Albergo, Theresa; Conroy, Suzanne; Dale, Alicia; Corbeil, Scott; Martakos, Paul; Edelman, Elazer R

    2016-03-01

    In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications. PMID:26502170

  8. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy

    PubMed Central

    2013-01-01

    Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources. PMID:23298332

  9. Multifunctional Environmental Smart Fertilizer Based on l-Aspartic Acid for Sustained Nutrient Release.

    PubMed

    Lü, Shaoyu; Feng, Chen; Gao, Chunmei; Wang, Xinggang; Xu, Xiubin; Bai, Xiao; Gao, Nannan; Liu, Mingzhu

    2016-06-22

    Fertilizer is one of the most important elements of modern agriculture. However, conventional fertilizer, when applied to crops, is vulnerable to losses through volatilization, leaching, nitrification, or other means. Such a loss limits crop yields and pollutes the environment. In an effort to enhance nutrient use efficiency and reduce environmental pollution, an environmental smart fertilizer was reported in the current study. Poly(aspartic acid) and a degradable macro-cross-linker based on l-aspartic acid were synthesized and introduced into the fertilizer as a superabsorbent to improve the fertilizer degradability and soil moisture-retention capacity. Sustained release behavior of the fertilizer was achieved in soil. Cumulative release of nitrogen and phosphorus was 79.8% and 64.4% after 30 days, respectively. The water-holding and water-retention capacities of soil with the superabsorbent are obviously higher than those of the control soil without superabsorbent. For the sample of 200 g of soil with 1.5 g of superabsorbent, the water-holding capacity is 81.8%, and the water-retention capacity remains 22.6% after 23 days. All of the current results in this study indicated that the as-prepared fertilizer has a promising application in sustainable modern agriculture. PMID:27244106

  10. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

  11. Concurrent release of admixed antimicrobials and salicylic acid from salicylate-based poly(anhydride-esters)

    PubMed Central

    Johnson, Michelle L.; Uhrich, Kathryn E.

    2008-01-01

    A polymer blend consisting of antimicrobials (chlorhexidine, clindamycin, and minocycline) physically admixed at 10% by weight into a salicylic acid-based poly (anhydride-ester) (SA-based PAE) was developed as an adjunct treatment for periodontal disease. The SA-based PAE/antimicrobial blends were characterized by multiple methods, including contact angle measurements and differential scanning calorimetry. Static contact angle measurements showed no significant differences in hydrophobicity between the polymer and antimicrobial matrix surfaces. Notable decreases in the polymer glass transition temperature (Tg) and the antimicrobials' melting points (Tm) were observed indicating that the antimicrobials act as plasticizers within the polymer matrix. In vitro drug release of salicylic acid from the polymer matrix and for each physically admixed antimicrobial was concurrently monitored by high pressure liquid chromatography during the course of polymer degradation and erosion. Although the polymer/antimicrobial blends were immiscible, the initial 24 h of drug release correlated to the erosion profiles. The SA-based PAE/antimicrobial blends are being investigated as an improvement on current localized drug therapies used to treat periodontal disease. PMID:19180627

  12. Controlled drug release from cross-linked κ-carrageenan/hyaluronic acid membranes.

    PubMed

    El-Aassar, M R; El Fawal, G F; Kamoun, Elbadawy A; Fouda, Moustafa M G

    2015-01-01

    In this work, hydrogel membrane composed of; kappa carrageenan (κC) and hyaluronic acid (HA) crosslinked with epichlorohydrine is produced. The optimum condition has been established based on their water absorption properties. Tensile strength (TS) and elongation (E%) for the formed films are evaluated. The obtained films were characterized by FTIR, scanning electron microscopy (SEM) and thermal analysis. All membranes were loaded with l-carnosine as a drug model. The swelling properties and kinetics of the release of the model drug from the crosslinked hydrogel membrane were monitored in buffer medium at 37°C. The equilibrium swelling of films showed fair dependency on the high presence of HA in the hydrogel. Moreover, the cumulative release profile increased significantly and ranged from 28% to 93%, as HA increases. SEM explored that, the porosity increased by increasing HA content; consequently, drug release into the pores and channels of the membranes is facilitated. In addition, water uptake % increased as well. A slight change in TS occurred by increasing the HA% to κC, while the highest value of strain for κC membrane was 498.38% by using 3% HA. The thermal stability of the κC/HA was higher than that of HA. PMID:25840148

  13. Surfactants modify the release from tablets made of hydrophobically modified poly (acrylic acid)☆

    PubMed Central

    Knöös, Patrik; Onder, Sebla; Pedersen, Lina; Piculell, Lennart; Ulvenlund, Stefan; Wahlgren, Marie

    2013-01-01

    Many novel pharmaceutically active substances are characterized by a high hydrophobicity and a low water solubility, which present challenges for their delivery as drugs. Tablets made from cross-linked hydrophobically modified poly (acrylic acid) (CLHMPAA), commercially available as Pemulen™, have previously shown promising abilities to control the release of hydrophobic model substances. This study further investigates the possibility to use CLHMPAA in tablet formulations using ibuprofen as a model substance. Furthermore, surfactants were added to the dissolution medium in order to simulate the presence of bile salts in the intestine. The release of ibuprofen is strongly affected by the presence of surfactant and/or buffer in the dissolution medium, which affect both the behaviour of CLHMPAA and the swelling of the gel layer that surrounds the disintegrating tablets. Two mechanisms of tablet disintegration were observed under shear, namely conventional dissolution of a soluble tablet matrix and erosion of swollen insoluble gel particles from the tablet. The effects of surfactant in the surrounding medium can be circumvented by addition of surfactant to the tablet. With added surfactant, tablets that may be insusceptible to the differences in bile salt level between fasted or fed states have been produced, thus addressing a central problem in controlled delivery of hydrophobic drugs. In other words CLHMPAA is a potential candidate to be used in tablet formulations for controlled release with poorly soluble drugs. PMID:25755999

  14. Modified hydroxypropyl methyl cellulose: Efficient matrix for controlled release of 5-amino salicylic acid.

    PubMed

    Das, Raghunath; Pal, Sagar

    2015-01-01

    Hydroxypropyl methyl cellulose has been modified by grafting synthetic polyacrylamide chains [g-HPMC (M)] in presence of microwave irradiation, which has used as carrier for controlled release of 5-amino salicylic acid (5-ASA). The FTIR and UV-vis-NIR studies reveal the excellent compatibility between g-HPMC (M) and 5-ASA. Field emission scanning electron microscopy (FESEM) and UV-vis-NIR analyses suggest that physical interaction predominates between the drug and matrix. % equilibrium swelling ratio (% ESR) of g-HPMC (M) decreased with addition of salt solutions and follow the order: Na(+)>K(+)>Mg(2+)>Ca(2+)>Al(3+). The in vitro 5-ASA release studies indicate that g-HPMC (M) delivers the drug preferentially in colonic region in more sustained way than that of HPMC. The 5-ASA release follows first order kinetics and non-Fickian diffusion mechanism. These favorable features make the graft copolymer a potential matrix for colon specific delivery of 5-ASA. PMID:25796452

  15. Fatty acids for controlled release applications: A comparison between prilling and solid lipid extrusion as manufacturing techniques.

    PubMed

    Vervaeck, A; Monteyne, T; Siepmann, F; Boone, M N; Van Hoorebeke, L; De Beer, T; Siepmann, J; Remon, J P; Vervaet, C

    2015-11-01

    The aim of the present study was to evaluate the solid state characteristics, drug release and stability of fatty acid-based formulations after processing via prilling and solid lipid extrusion. Myristic acid (MA), stearic acid (SA) and behenic acid (BA) were used as matrix formers combined with metoprolol tartrate (MPT) as model drug. The prilling process allowed complete dissolution of MPT in the molten fatty acid phase, generating semi-crystalline MPT and the formation of hydrogen bonds between drug and fatty acids in the solid prills. In contrast, as solid lipid extrusion (SLE) induced only limited melting of the fatty acids, molecular interaction with the drug was inhibited, yielding crystalline MPT. Although the addition of a low melting fatty acid allowed more MPT/fatty acid interaction during extrusion, crystalline MPT was detected after processing. Mathematical modeling revealed that the extrudates exhibited a higher apparent drug/water mobility than prills of the same composition, probably due to differences in the inner systems' structure. Irrespective of the processing method, mixed fatty acid systems (e.g. MA/BA) exhibited a lower matrix porosity, resulting in a slower drug release rate. Solid state analysis of these systems indicated that the crystalline structure of the fatty acids was maintained after SLE, while prilling generated a reduced MA crystallinity. Binary MPT/fatty acid systems processed via extrusion showed better stability during storage at 40 °C than the corresponding prills. Although mixed fatty acid systems were stable at 25 °C, stability problems were encountered during storage at 40 °C: a faster release was obtained from the prills, whereas drug release from the extrudates was slower. PMID:26428938

  16. [Absolute bioavailability of a special sustained-release acetylsalicylic acid formulation].

    PubMed

    Lücker, P W; Swoboda, M; Wetzelsberger, N

    1989-03-01

    Absolute Bioavailability of a Special Acetylsalicylic Acid Sustained Release Formulation. The absolute bioavailability of an acetylsalicylic acid (ASA) sustained release formulation (Contrheuma retard), containing 300 mg ASA as initial dose and 350 mg in a retard formulation, was determined in comparison to a standard ASA solution for intravenous administration in a two-treatment, two-period cross-over trial with 6 healthy male volunteers by comparing the areas under the plasma-fluctuation-time curves of the primary metabolite. In addition, it was examined by comparison of the mean times after administration of both formulations, whether the test formulation meets the requirements of a sustained release formulation. The investigations led to the following results: The absolute bioavailability of the test formulation was 95%. The statistical comparison of the areas under the concentration-time courses allowed no decision (neither for equivalence nor difference). The maximal concentration of SA after intravenous administration of the standard formulation was reached after 0.4 h on an average and amounted to 62 micrograms/ml. After oral administration of the test formulation, a mean concentration maximum of 28 micrograms/ml was calculated, which had been reached after about 2 h. The differences are statistically significant. The mean time for SA was 6 h after the standard formulation, whereas after administration of the test compound, a mean of 11.5 h was calculated. 24 h following administration, the concentration of SA was 1.3 micrograms/ml after intravenous administration of the standard formulation and 5.5 micrograms/ml after administration of the test formulation. These differences, too, are statistically significant. From the comparison of the mean time for SA, a retard factor of 1.9 was calculated. PMID:2757664

  17. Regulation of luteinizing hormone-releasing hormone and luteinizing hormone secretion by hypothalamic amino acids.

    PubMed

    Donoso, A O; Seltzer, A M; Navarro, C E; Cabrera, R J; López, F J; Negro-Vilar, A

    1994-04-01

    1. The present review discusses the proposed roles of the amino acids glutamate and GABA in the central regulation of luteinizing hormone-releasing hormone (LHRH) and in luteinizing hormone (LH) secretion. 2. Descriptions of the mechanisms of action of these neurotransmitters have focused on two diencephalic areas, namely, the preoptic-anterior hypothalamic area where the cell bodies of LHRH neurons are located, and the medial basal hypothalamus which contains the nerve endings of the LHRH system. Increasing endogenous GABA concentration by drugs, GABA agonists, or blockade of glutamatergic neurotransmission by selective antagonists in rats and non-human primates prevents ovulation and pulsatile LH release, and blunts the LH surges induced by estrogen or an estrogen-progesterone combination. In contrast, glutamate and different glutamate agonists such as NMDA, AMPA and kainate, can increase LHRH/LH secretion. 3. The simultaneous enhancement of glutamatergic activity and a decrease of GABAergic tone may positively influence the maturation of the pituitary-gonadal system in rats and non-human primates. Administration of glutamate receptor agonists has been shown to significantly advance the onset of puberty. Conversely, glutamate antagonists or increased endogenous GABA levels may delay the onset of puberty. The physiological regulation of LHRH/LH secretion may thus involve a GABA-glutamate interaction and a cooperative action of the various types of ionotropic glutamate receptors. 4. The inhibitory actions of GABA on LH release and ovulation may be exerted at the level of afferent nerve terminals that regulate LHRH secretion. A likely candidate is noradrenaline, as suggested by the synaptic connections between noradrenergic nerve terminals and GABAergic interneurons in the preoptic area. Recent experiments have provided complementary evidence for the physiological balance between inhibitory and excitatory transmission resulting in modulation of the action of

  18. Release of cetyl pyridinium chloride from fatty acid chelate temporary dental cement

    PubMed Central

    Hurt, Andrew; Coleman, Nichola J.; Tüzüner, Tamer; Bagis, Bora; Korkmaz, Fatih Mehmet; Nicholson, John W.

    2016-01-01

    Abstract Objective To determine whether the antimicrobial nature of a fatty acid chelate temporary dental cement can be enhanced by the addition of 5% cetyl pyridinium chloride (CPC). Materials and methods The temporary cement, Cavex Temporary was employed, and additions of CPC were made to either the base or the catalyst paste prior to mixing the cement. Release of CPC from set cement specimens was followed using reverse-phase HPLC for a period of up to 2 weeks following specimen preparation. Potential interactions between Cavex and CPC were examined by Fourier transform infrared spectroscopy (FTIR) and antimicrobial effects were determined using zone of inhibition measurements after 24 h with disc-shaped specimens in cultured Streptococcus mutans. Results FTIR showed no interaction between CPC and the components of the cement. CPC release was found to follow a diffusion mechanism for the first 6 h or so, and to equilibrate after approximately 2 weeks, with no significant differences between release profiles when the additive was incorporated into the base or the catalyst paste. Diffusion was rapid, and had a diffusion coefficient of approximately 1 × 10−9 m2 s−1 in both cases. Total release was in the range 10–12% of the CPC loading. Zones of inhibition around discs containing CPC were significantly larger than those around the control discs of CPC-free cement. Conclusions The antimicrobial character of this temporary cement can be enhanced by the addition of CPC. Such enhancement is of potential clinical value, though further in vivo work is needed to confirm this. PMID:27335898

  19. Effects of sufentanil on the release and metabolism of dopamine and ascorbic acid and glutamate release in the striatum of freely moving rats.

    PubMed

    Serra, Pier Andrea; Susini, Giuseppe; Rocchitta, Gaia; Migheli, Rossana; Dessanti, Giuseppina; Miele, Egidio; Desole, Maria Speranza; Miele, Maddalena

    2003-06-19

    The effects of either intraperitoneally (i.p.) or intrastriatally administered sufentanil on the release and metabolism of dopamine (DA) in the rat striatum were evaluated using in vivo microdialysis. Dialysate concentrations of DA and its acidic metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased following i.p. administration of either clinical anesthetic (20 microg/kg) or clinical analgesic (1 microg/kg) sufentanil doses. In addition, sufentanil also increased uric acid concentrations. In contrast, dialysate ascorbic acid and glutamate concentrations were unaffected. Intrastriatal infusion of sufentanil (250 nM) induced only a short lasting decrease in dialysate DA. Subcutaneous naloxone (1.0 mg/kg) abolished sufentanil-induced increases in dialysate DA, DOPAC+HVA and uric acid; however, naloxone (0.1 mM) failed to affect these increases when infused intrastriatally. These results demonstrate that sufentanil, at clinical doses, increases striatal DA release and oxidative metabolism of both DA and xanthine acting at extrastriatal sites with a mu-receptor-mediated mechanism. PMID:12781909

  20. The release of histamine during gastric acid secretion in conscious rats

    PubMed Central

    el Munshid, H. A.; Lake, H. J.

    1974-01-01

    1. Conscious gastric-cannulated rats were given [3H]histidine and aminoguanidine by dosage procedures intended to build up fast-turnover and slow-turnover pools of tissue [3H]histamine. Acid secretion was stimulated by I.V. infusion of pentagastrin, and the [3H]histamine content of gastric juice and excretion in urine were determined at 30 min intervals. 2. The amount of [3H]histamine in gastric juice derived from either a slow-turnover or fast-turnover pool was very low in unstimulated animals, and was not altered during pentagastrin-stimulated acid secretion. 3. From a slow-turnover pool pentagastrin caused increased urinary excretion of [3H]histamine. This was abolished by gastrectomy, so that the [3H]histamine liberated by pentagastrin from this pool appears to have been derived from the stomach. Evidence was not found for the existence of a slow-turnover histamine pool in the glandular mucosa of the stomach, and the source within the stomach of this pentagastrin-liberated histamine is thus uncertain. 4. From a fast-turnover pool pentagastrin did not cause an increased urinary excretion of [3H]histamine. The amount of [3H]histamine excreted by gastrectomized rats was not different from that produced by gastric-cannulated animals. This suggests that a high proportion of urinary histamine derived from a fast-turnover pool was non-gastric in origin. 5. Differences in the time scale of [3H]histamine release and acid secretion were not found. In some experiments the urinary output of [3H]histamine was prolonged beyond the end of pentagastrin administration and gastric acid secretion. However, the overall data do not suggest that urinary histamine output and gastric acid secretion take different time courses. PMID:4141368

  1. Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-06-01

    Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers. PMID:27040215

  2. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    SciTech Connect

    Amin, D.

    1986-01-01

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with (/sup 14/C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A/sub 2/ activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents.

  3. Nicotinic acid: new/old drug. Immediate or sustained release: too risky for a drug with no proven benefit.

    PubMed

    2006-12-01

    (1) For patients with hypercholesterolaemia requiring primary or secondary prevention, pravastatin, simvastatin and atorvastatin have a proven benefit in terms of mortality and/or morbidity. Gemfibrozil and cholestyramine have a proven impact on morbidity. (2) The lipid-lowering properties of immediate-release nicotinic acid have been known for about 50 years, as have its frequent and sometimes severe adverse effects. About 70% of patients experience cutaneous flushing, and 20-30% develop gastrointestinal adverse effects. Hepatotoxic effects occur in about 2% of patients, especially in those using high daily doses or sustained-release formulations. (3) The clinical evaluation of immediate-release nicotinic acid is mainly based on two comparative placebo-controlled trials. One, involving 5000 patients monitored on average for 15 years, showed no effect on survival. One trial suggested that immediate-release nicotinic acid reduced the risk of recurrent myocardial infarction. (4) Sustained-release nicotinic acid has not been evaluated in terms of its effect on morbidity or mortality. It has been shown to lower LDL cholesterol and triglyceride levels and to raise the HDL cholesterol level. (5) This new pharmaceutical formulation has a profile and frequency of known adverse effects similar to those of immediate-release nicotinic acid. (6) When hypercholesterolaemia persists despite an appropriate diet, it is best to use one drug with a proven preventive impact on mortality and/or morbidity. This is not the case for sustained-release nicotinic acid. (7) When statin therapy is inadequate, it remains to be shown whether adding another cholesterol-lowering drug is beneficial in terms of morbidity and mortality. If, in rare cases, combination with a statin is envisaged, it is best to use gemfibrozil or cholestyramine. Note that gemfibrozil should only be combined with a statin with the greatest caution. PMID:17165243

  4. Diazeniumdiolate-Doped Poly(lactic-co-glycolic acid)-Based Nitric Oxide Releasing Films as Antibiofilm Coatings

    PubMed Central

    Cai, Wenyi; Wu, Jianfeng; Xi, Chuanwu; Meyerhoff, Mark, E.

    2012-01-01

    Nitric oxide (NO) releasing films with a bilayer configuration are fabricated by doping dibutyhexyldiamine diazeniumdiolate (DBHD/N2O2) in a poly(lactic-co-glycolic acid) (PLGA) layer and further encapsulating this base layer with a silicone rubber top coating. By incorporating pH sensitive dyes within the films, pH changes in the PLGA layer are visualized and correlated with the NO release profiles (flux vs. time). It is demonstrated that PLGA acts as both a promoter and controller of NO release from the coating by providing protons through its intrinsic acid residues (both end-groups and monomeric acid impurities) and hydrolysis products (lactic acid and glycolic acid). Control of the pH changes within the PLGA layer can be achieved by adjusting the ratio of DBHD/N2O2 and utilizing PLGAs with different hydrolysis rates. Coatings with a variety of NO release profiles are prepared with lifetimes of up to 15 d at room temperature (23 °C) and 10 d at 37 °C. When incubated in a CDC flow bioreactor for a one-week period at RT or 37 °C, all the NO releasing films exhibit considerable antibiofilm properties against gram-positive S. aureus and gram-negative E. coli. In particular, compared to the silicone rubber surface alone, an NO releasing film with a base layer of 30 wt% DBHD/N2O2 mixed with poly(lactic acid) exhibits an ~98.4% reduction in biofilm biomass of S. aureus and ~ 99.9% reduction for E. coli at 37 °C. The new diazeniumdiolate-doped PLGA-based NO releasing coatings are expected to be useful antibiofilm coatings for a variety of indwelling biomedical devices (e.g., catheters). PMID:22841918

  5. Differential effects of eicosapentaenoic and docosahexaenoic acids upon oxidant-stimulated release and uptake of arachidonic acid in human lymphoma U937 cells.

    PubMed

    Obajimi, Oluwakemi; Black, Kenneth D; MacDonald, Donald J; Boyle, Rose M; Glen, Iain; Ross, Brian M

    2005-08-01

    The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary supplements, as anti-inflammatory agents is supported by a variety of biochemical and physiological data. Recent studies investigating the therapeutic potential of long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion, however, that not all n-3 fatty acid types are equally efficacious. In particular eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be due to a differential ability to antagonize arachidonic acid (AA)-dependent cell signalling. In this study, we examine the effect of EPA and DHA supplementation upon uptake and release of arachidonic acid stimulated by tert-butyl hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids for 18 days, with the order of effect magnitude being EPA > DHA = AA. Supplementation of cells for 1 day gave qualitatively similar results, although the effect magnitude was smaller. To determine whether enhanced release was due to decreased reuptake of AA, cells were cultured in the presence of 10 microM fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of uptake and release of AA from phospholipids in an exposure time-dependent manner, whereas DHA has no or little effect. Our results predict that EPA will have a more pronounced effect upon AA-dependent processes compared to DHA, and suggests that the relative amounts of EPA and DHA in fish oil supplements may modify their biochemical, and potentially, behavioural effects. PMID:15967385

  6. Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Tomić, S. Lj.; Mićić, M. M.; Filipović, J. M.; Suljovrujić, E. H.

    2007-05-01

    The new copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were prepared by gamma irradiation, in order to examine the potential use of these hydrogels in controlled drug release systems. The influence of IA content in the gel on the swelling characteristics and the releasing behavior of hydrogels, and the effect of different drugs, theophylline (TPH) and fenethylline hydrochloride (FE), on the releasing behavior of P(HEMA/IA) matrix were investigated in vitro. The diffusion exponents for swelling and drug release indicate that the mechanisms of buffer uptake and drug release are governed by Fickian diffusion. The swelling kinetics and, therefore, the release rate depends on the matrix swelling degree. The drug release was faster for copolymeric hydrogels with a higher content of itaconic acid. Furthermore, the drug release for TPH as model drug was faster due to a smaller molecular size and a weaker interaction of the TPH molecules with(in) the P(HEMA/IA) copolymeric networks.

  7. Actions of a tremorgenic mycotoxin on amino acid transmitter release in vivo.

    PubMed

    Peterson, D W; Bradford, H F; Mantle, P G

    1982-09-01

    The tremorgenic mycotoxin verruculogen was administered directly into the brain of freely moving rats by the use of cannula systems that superfused either the cortical surface or the lateral ventricular space. The tremor produced by these CNS routes was compared with that produced by i.p. administration of the toxin or the dried mycelium of the fungus that synthesizes the verruculogen. The nature and degree of tremor produced by the central vs peripheral routes suggest that the site of action of verruculogen is not immediately adjacent to the cannula sites in the brain. Measures of the amino acids in the superfusates collected during the verruculogen-induced tremor showed an increase in the excitatory neurotransmitters, glutamate and aspartate in superfusates from the lateral ventricle but not in superfusates from the cortical surface. The differential effect on transmitter release suggests that a subcortical action of verruculogen is responsible for its tremorgenic activity. PMID:6128004

  8. Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization.

    PubMed

    Bates, Ryan C; Fees, Colby P; Holland, William L; Winger, Courtney C; Batbayar, Khulan; Ancar, Rachel; Bergren, Todd; Petcoff, Douglas; Stith, Bradley J

    2014-02-01

    We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC-γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca](i)). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 min after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca](i) and other fertilization events. As compared to 14 other lipids, PA specifically bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca](i), PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca](i) release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca](i) release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization. PMID:24269904

  9. Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization

    PubMed Central

    Bates, Ryan C.; Fees, Colby P.; Holland, William L.; Winger, Courtney C.; Batbayar, Khulan; Ancar, Rachel; Bergren, Todd; Petcoff, Douglas; Stith, Bradley J.

    2014-01-01

    We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC- γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca]i). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 minute after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca]i and other fertilization events. As compared to 14 other lipids, PA strongly bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca]i, PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca]i release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca]i release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization. PMID:24269904

  10. Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging.

    PubMed

    Jia, Xuekun; Yin, Jinjin; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Chen, Mian; Li, Yuhong

    2013-12-01

    A poly(acrylicacid)-modified NaYF4:Yb, Er upconversion nanoparticles (PAA-UCNPs) with dual functions of drug delivery and release imaging have been successfully developed. The PAA polymer coated on the surface of UCNPs serve as a pH-sensitive nanovalve for loading drug molecules via electrostatic interaction. The drug-loading efficiency of the PAA-UCNPs was investigated by using doxorubicin hydrochloride (DOX) as a model anticancer drug to evaluate their potential as a delivery system. Results showed loading and releasing of DOX from PAA-UCNPs were controlled by varying pH, with high encapsulation rate at weak alkaline conditions and an increased drug dissociation rate in acidic environment, which is favorable for construct a pH-responsive controlled drug delivery system. The in vitro cytotoxicity test using HeLa cell line indicated that the DOX loaded PAA-UCNPs (DOX@PAA-UCNPs) were distinctly cytotoxic to HeLa cells, while the PAA-UCNPs were highly biocompatible and suitable to use as drug carriers. Furthermore, the upconversion fluorescence resonance energy transfer (UFRET) imaging through the two-photon laser scanning microscopy (TLSM) revealed the time course of intracellular delivery of DOX from DOX@PAA-UCNPs. Thus, PAA-UCNPs are effective for constructing pH-responsive controlled drug delivery systems for multi-functional cancer therapy and imaging. PMID:24266261

  11. Doxorubicin hydrochloride-oleic acid conjugate loaded nanostructured lipid carriers for tumor specific drug release.

    PubMed

    Zhao, Shuangni; Minh, Le Van; Li, Na; Garamus, Vasil M; Handge, Ulrich A; Liu, Jianwen; Zhang, Rongguang; Willumeit-Römer, Regine; Zou, Aihua

    2016-09-01

    The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment. PMID:27137808

  12. Noble Gases and Nitrogen Released from a Lunar Soil Pyroxene Separate by Acid Etching

    NASA Astrophysics Data System (ADS)

    Rider, P. E.

    1993-07-01

    We report initial results from a series of experiments designed to measure recently implanted solar wind (SW) ions in lunar soil mineral grains [1]. An acid-etching technique similar to the CSSE method developed at ETH Zurich was used to make abundance and isotope measurements of the SW noble gas and nitrogen compositions. Among the samples examined was a pyroxene separate from soil 75081. It was first washed with H2O to remove contamination from the sample finger walls and grain surfaces. H2O also acted as a weak acid, releasing gases from near-surface sites. Treatment with H2SO3 followed the water washes. Acid pH (~1.8 to ~1.0) and temperature (~23 degrees C to ~90 degrees C) and duration of acid attack (several minutes to several days) were varied from step to step. Finally, the sample was pyrolyzed in several steps to remove the remaining gases, culminating with a high-temperature pyrolysis at 1200 degrees C. Measurements of the light noble gases were mostly consistent with those from previous CSSE experiments performed on pyroxene [2,3]. It should be noted, however, that the Zurich SEP component was not easily distinguishable in the steps where it was expected to be observed. We suspect our experimental protocol masked the SEP reservoir, preventing us from seeing its distinctive signature. The most interesting results from this sample are its Kr and Xe isotopic and elemental compositions. Pyroxene apparently retains heavy noble gases as well as ilmenite (and plagioclase [4]). The heavy noble gas element ratios from this sample along with those previously reported [5,6] are, however, considerably heavier than the theoretically determined "solar system" values [7,8]. Explanations for the difference include the possibility that the derivations are incorrect, that there is another component of lunar origin mixing with the solar component, or that some type of loss mechanism is altering the noble gas reservoirs of the grains. The Kr and Xe isotopic compositions for

  13. Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus.

    PubMed

    Kaehler, S T; Sinner, C; Kouvelas, D; Philippu, A

    2000-02-01

    We investigated the importance of endogenous amino acids in the locus coeruleus in inescapable electric shock and conditioned fear. In naive rats and in rats exposed to noise (N), light (L) and electric shock (S) or to N + L only, the locus coeruleus was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of GABA, taurine, glutamate, aspartate, serine and glutamine was determined in the superfusate by HPLC after derivatization with o-phthaldialdehyde. Locomotor activity, arterial blood pressure and heart rate were telemetrically monitored. The placement of naive rats or conditioned rats from their home cage to a chamber provided with a grid-floor for shock virtually did not change the release rates of the amino acids in the locus coeruleus. Motility was enhanced in naive and conditioned rats to a similar extent. Blood pressure and heart rate were enhanced in conditioned rats only. Exposure to N + L + S for 5 min greatly enhanced the release rates of all determined amino acids in the locus coeruleus. In conditioned rats the increase in release of most amino acids lasted longer than in naive rats. Electric shock also enhanced motility, blood pressure and heart rate. In conditioned rats, motility and cardiovascular changes were more pronounced and/or lasted longer than in naive rats. Exposure of conditioned rats to the conditioned stimuli N + L for 5 min led to an increased release of taurine and aspartate. The enhanced release of taurine lasted 30 min. Exposure to N + L did not affect the release rates of amino acids in naive rats. N + L did not influence motility but arterial blood pressure and heart rate were elevated in conditioned rats. The findings show that inescapable electric shock enhances the release of several amino acids in the locus coeruleus, while conditioned fear selectively increases the outflow of taurine and aspartate. Moreover, conditioned fear prolongs the response of excitatory and inhibitory amino acids to

  14. Radiation synthesis of poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels and their controlled release behaviours

    NASA Astrophysics Data System (ADS)

    Şen, M.; Güven, O.

    1999-06-01

    N-vinyl 2-pyrrolidone/itaconic acid copolymeric hydrogels were prepared by irradiating the ternary mixtures of N-vinyl 2-pyrrolidone/itaconic acid/water by γ-rays at ambient temperature. For the characterization of network structure of these hydrogels, swelling properties in phosphate buffer solutions and molecular weight between crosslinks were investigated. Methylene Blue was used as a model drug for the investigation of controlled release behaviour of hydrogels. Specific Methylene Blue adsorption capacity of hydrogels are found to increase from 0.36 to 47.7 (mg MB/g gel) with increasing amount of itaconic acid in the gel system. The influence of molecular weight between cross-links, the concentration of ionizable groups, ionization and concentration of MB in the hydrogel were examined. The release studies show that one of the basic parameters affecting the drug release behaviour of hydrogels is the pH of the solution.

  15. New type of chitosan/2-hydroxypropyl-β-cyclodextrin composite membrane for gallic acid encapsulation and controlled release.

    PubMed

    Paun, Gabriela; Neagu, Elena; Tache, Andreia; Radu, G L

    2014-01-01

    A new type of chitosan/2-hydroxypropyl-β-cyclodextrin composite membrane have been developed for the encapsulation and controlled release of gallic acid. The morphology of the composite membrane was investigated by infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM), whereas swelling gallic acid and release properties were investigated by UV-visible spectroscopy. The release behavior with pH changes was also explored. The composite membrane based on chitosan/2-hydroxypropyl-β-cyclodextrin with gallic acid included showed improved antioxidant capacities compared to plain chitosan membrane. The information obtained in this study will facilitate the design and preparation of composite membrane based on chitosan and could open a wide range of applications, particularly its use as an antioxidant in food, food packaging, biomedical (biodegradable soft porous scaffolds for enhance the surrounding tissue regeneration), pharmaceutical and cosmetics industries. PMID:24664323

  16. Contrast of volatile fatty acid driven and inorganic acid or base driven phosphorus release and uptake in enhanced biological phosphorus removal.

    PubMed

    Randall, Andrew A

    2012-04-01

    Addition of an inorganic acid or base was detrimental to net phosphorus removals in short-term batch experiments, suggesting there might be system upset when pH changes. In contrast, addition of volatile fatty acids (VFAs) increased anaerobic phosphorus release and aerobic phosphorus uptake while maintaining or improving net phosphorus removals. The effect of pH change differed if the acid or base added was inorganic versus organic. Volatile fatty acids that resulted in poly-3-hydroxy-butyrate rather than poly-3-hydroxy-valerate resulted in greater net phosphorus removals, and this corresponded to differences in consumption of reducing equivalents. Acetic acid resulted in improved net phosphorus removal compared to sodium acetate, suggesting that acid forms of VFAs might be superior as supplemental VFAs. It is hypothesized that anaerobic phosphorus release following addition of inorganic acid is primarily a result of phosphorus and proton (H+) symport (excretion from the cell) for pH homeostasis, whereas addition of VFAs results in phosphorus and H+ release to maintain the proton motive force. PMID:22834218

  17. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pandey, Sanjeev K; Patel, Dinesh K; Maurya, Akhilendra K; Thakur, Ravi; Mishra, Durga P; Vinayak, Manjula; Haldar, Chandana; Maiti, Pralay

    2016-08-01

    Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer. PMID:27112980

  18. Involvement of L-type-like amino acid transporters in S-nitrosocysteine-stimulated noradrenaline release in the rat hippocampus.

    PubMed

    Satoh, S; Kimura, T; Toda, M; Maekawa, M; Ono, S; Narita, H; Miyazaki, H; Murayama, T; Nomura, Y

    1997-11-01

    Nitrogen oxides, such as nitric oxide, have been shown to regulate neuronal functions, including neurotransmitter release. We investigated the effect of S-nitroso-L-cysteine (SNC) on noradrenaline (NA) release in the rat hippocampus in vivo and in vitro. SNC stimulated [3H]NA release from prelabeled hippocampal slices in a dose-dependent manner. SNC stimulated endogenous NA release within 30 min to almost five times the basal level in vivo (microdialysis in freely moving rats). In a Na+-containing Tyrode's buffer, SNC-stimulated [3H]NA release was inhibited 30% by the coaddition of L-leucine. In the Na+-free, choline-containing buffer, SNC-stimulated [3H]NA release, which was similar to that in the Na+-containing buffer, was inhibited markedly by L-leucine, L-alanine, L-methionine, L-phenylalanine, and L-tyrosine. The effects of the other amino acids examined were smaller or very limited. The effect of L-leucine was stronger than that of D-leucine. A specific inhibitor of the L-type amino acid transporter, 2-aminobicyclo[2.2.1]-heptane-2-carboxylate (BCH), inhibited the effects of SNC on [3H]NA release in the Na+-free buffer. Uptake of L-[3H]leucine into the slices in the Na+-free buffer was inhibited by SNC, BCH, and L-phenylalanine, but not by L-lysine. The effect of SNC on cyclic GMP accumulation was not inhibited by L-leucine, although SNC stimulated cyclic GMP accumulation at concentrations up to 25 microM, much less than the concentration that stimulates NA release. These findings suggest that SNC is incorporated into rat hippocampus via the L-type-like amino acid transporter, at least in Na+-free conditions, and that SNC stimulates NA release in vivo and in vitro in a cyclic GMP-independent manner. PMID:9349567

  19. Dissociated effects of corticotropin-releasing factor on acid secretion and blood flow.

    PubMed

    Thiefin, G; Leung, F W; Tache, Y; Guth, P H

    1989-02-01

    Peripherally administered corticotropin-releasing factor (CRF) inhibits gastric acid secretion in the rat via unknown mechanisms. Because intravenous CRF can produce marked systemic hypotension, the hypothesis that its antisecretory effect is due to a reduction in gastric mucosal blood flow (MBF) was tested. Corpus MBF was measured by hydrogen gas clearance in fasted, urethan-anesthetized rats. CRF (15 nmol.kg-1.h-1 iv) had no significant effect on MBF but significantly decreased systemic blood pressure (BP) by 21.8 +/- 3.4%. This dose of CRF significantly decreased acid secretion stimulated by 40 micrograms.kg-1.h-1 pentagastrin iv but did not decrease MBF despite a 30.3 +/- 2.3% decrease in BP. To avoid the confounding effect of systemic hypotension on MBF, close gastric intra-arterial infusions were performed. CRF (1.7 nmol/h ia) had no effect on BP and did not increase MBF. CRF (3.4 nmol/h ia) slightly decreased BP without modifying MBF. In contrast, histamine (200 micrograms/h ia) significantly increased MBF by 58 +/- 11%. We conclude that 1) the peripheral antisecretory effect of CRF is not related to a decrease in MBF, 2) the maintenance of MBF during CRF-induced hypotension is not due to a direct vasodilator effect of CRF on the gastric microvasculature. PMID:2784035

  20. Xanthurenic acid distribution, transport, accumulation and release in the rat brain.

    PubMed

    Gobaille, Serge; Kemmel, Véronique; Brumaru, Daniel; Dugave, Christophe; Aunis, Dominique; Maitre, Michel

    2008-05-01

    Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre-synaptic terminals. A neuronal transport, partially dependant on adenosine 5'-triphosphate (ATP), sodium and chloride ions exists in NCB-20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions. Finally, electrical in vivo stimulation of A10-induced Xa release in the extracellular spaces of the rat prefrontal cortex. This phenomenon is reproduced by veratrine, K+ ions and blocked by EGTA and tetrodotoxin. These results strongly argue for a role for Xa in neurotransmission/neuromodulation in the rat brain, thus providing the existence of specific Xa receptors. PMID:18182052

  1. Cellulose crosslinked pH-responsive polyurethanes for drug delivery: α-hydroxy acids as drug release modifiers.

    PubMed

    Solanki, Archana; Thakore, Sonal

    2015-09-01

    Cellulose crosslinked waterborne polyurethanes (PUs) based on poly ɛ-caprolactone with lactic acid/glycolic acid/dimethylol-propionic acid as a drug release modifiers cum chain extenders were prepared. PUs were loaded with felodipine and drug release was monitored at different pH values. The structure of the polymers was characterized by FTIR, DSC & TGA and SEM. The encapsulation of dug inside PU matrix and the morphology of polymer after drug release were studied by using SEM. All the PUs were observed to degrade under highly basic conditions. The PUs act as pH sensitive drug carriers with an added advantage of modulated release rate as a function of acid chain extenders. The rate of release of the drug was significantly faster at pH 7.4 as compared to gastric pH 1.2, with same incubation time. The PUs reported in the present study may be suitable for medical applications like vaginal drug delivery and colon specific drug delivery. PMID:26188306

  2. Low-molecular-weight solutes released during mild acid hydrolysis of the lipopolysaccharide of Pseudomonas aeruginosa. Identification of ethanolamine triphosphate

    PubMed Central

    Drewry, David T.; Gray, George W.; Wilkinson, Stephen G.

    1972-01-01

    A careful examination of the low-molecular-weight solutes released during mild acid hydrolysis of the lipopolysaccharide of Pseudomonas aeruginosa (N.C.T.C. 1999) revealed the presence of ethanolamine triphosphate. During storage, the compound decomposed to give ethanolamine pyrophosphate, identified in a previous study (Drewry et al., 1971); PPi may be a further decomposition product. Evidence for the attachment of ethanolamine triphosphate to a polysaccharide fraction was obtained, but the possibility that some was attached to the lipid A moiety was not excluded. Basic compounds released during the hydrolysis of lipopolysaccharide included amino acids, polyamines and oligopeptides. PMID:4632171

  3. In vitro ozone exposure increases release of arachidonic acid products from a human bronchial epithelial cell line

    SciTech Connect

    McKinnon, K.P.; Madden, M.C.; Noah, T.L.; Devlin, R.B. )

    1993-02-01

    Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), LTD4, LTE4, and 12-hydroxyheptadecatrienoic acid (HHT) after exposure to ozone at concentrations of 0.1, 0.25, 0.5, and 1.0 ppm. The eicosanoids were identified by coelution with authentic standards. The largest product from ozone-exposed BEAS cells was the most polar peak, designated Peak 1. Release of cyclooxygenase products such as TxB2, PGE2, and HHT was inhibited by acetylsalicylic acid. Peaks that migrated with authentic standards for LTB4, LTC4, and LTD4 were inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid. The leukotrienes LTB4 and LTC4/D4 could also be detected by immunoassay of concentrated peak fractions. Thus BEAS cells released eicosanoids from cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism following exposure to ozone. Airway epithelial cells may be an important source of eicosanoids following ozone stimulation in humans.

  4. Clostridium thermocellum releases coumaric acid during degradation of untreated grasses by the action of an unknown enzyme.

    PubMed

    Herring, Christopher D; Thorne, Philip G; Lynd, Lee R

    2016-03-01

    Clostridium thermocellum is an anaerobic thermophile with the ability to digest lignocellulosic biomass that has not been pretreated with high temperatures. Thermophilic anaerobes have previously been shown to more readily degrade grasses than wood. Part of the explanation for this may be the presence of relatively large amounts of coumaric acid in grasses, with linkages to both hemicellulose and lignin. We found that C. thermocellum and cell-free cellulase preparations both release coumaric acid from bagasse and switchgrass. Cellulase preparations from a mutant strain lacking the scaffoldin cipA still showed activity, though diminished. Deletion of all three proteins in C. thermocellum with ferulic acid esterase domains, either singly or in combination, did not eliminate the activity. Further work will be needed to identify the novel enzyme(s) responsible for the release of coumaric acid from grasses and to determine whether these enzymes are important factors of microbial biomass degradation. PMID:26762388

  5. Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue.

    PubMed Central

    Jhamandas, K.; Marien, M.

    1987-01-01

    The present study examined the effect of a selective delta-opioid receptor agonist [D-Ala2-D-Leu5] enkephalin (DADL) on the spontaneous and the L-glutamic acid (L-Glu)-evoked release of endogenous dopamine from superfused slices of rat caudate-putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d.) after a two-step separation procedure. The spontaneous release of endogenous dopamine was partially dependent on Ca2+, enhanced in Mg2+-free superfusion medium, partially reduced by tetrodotoxin (TTX, 0.3 microM), partially reduced by the putative excitatory amino acid receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (DL-APH, 1 mM), and increased 10 fold by the dopamine uptake blocker, nomifensine (10 microM). DADL (5 and 50 nM) did not significantly affect spontaneous dopamine release. L-Glu (0.1-10 mM) produced a concentration-dependent release of endogenous dopamine from slices of caudate-putamen. This effect was Ca2+-dependent, strongly inhibited by 1.2 mM Mg2+, attenuated by DL-APH (1 mM), attenuated by TTX (0.3 microM), and enhanced by nomifensine (10 microM). In the presence of nomifensine DADL (50 nM) reduced significantly the L-Glu-evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 microM naloxone. These results indicate that L-Glu stimulates the Ca2+-dependent release of endogenous dopamine in the caudate-putamen by activation of N-methy-D-aspartate-type of excitatory amino acid receptors. This release can be selectively modified by the delta-opioid agonist DADL in a naloxone-sensitive manner. PMID:2884003

  6. Comparison of alkali treatments for efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith.

    PubMed

    Jiang, Kankan; Li, Lulu; Long, Liangkun; Ding, Shaojun

    2016-05-01

    Two separate temperature and time ranges were respectively conducted for optimizing release of p-coumaric acid and enzymatic saccharification of sorghum pith by NaOH pretreatment using response surface methodology. Two desirable pretreatment conditions were selected as follows: 37°C, 2% NaOH and 12h, and 100°C, 1.75% NaOH and 37min in the low and high temperature ranges, respectively. Under these conditions, the enzymatic glucose yields were 85.6% and 90.4% respectively, whereas p-coumaric acid yields were 95.1% and 98.1% respectively. The final recovery of esterified p-coumaric acid reached 82.8% and 87.4% respectively after further separation with HP-20 resin. Interestingly, strong linear correlations exist between p-coumaric acid release with glucan saccharification yield and lignin dissolution. These results indicate that sorghum pith could be an attractive source for natural p-coumaric acid and efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith can be achieved by mild NaOH pretreatment. PMID:26868149

  7. Acute health effects in a community after a release of hydrofluoric acid

    SciTech Connect

    Wing, J.S.; Brender, J.D.; Sanderson, L.M.; Perrotta, D.M.; Beauchamp, R.A. )

    1991-05-01

    {approximately} 3,000 persons were evacuated from a Texas community after 24,036 kg (53,000 lb) of caustic hydrofluoric acid (HF) were released from a nearby petrochemical plant. Emergency room and hospital records of 939 persons who were seen at two area hospitals were reviewed. Most persons who presented at the emergency rooms were female (56%) or black (60%), and their mean age was 33.9 y. The most frequently reported symptoms were eye irritation (41.5%), burning throat (21%), headache (20.6%), and shortness of breath (19.4%). Physical examination results were normal for 49% of the cases; however, irritation of the eyes, nose, throat, skin, and lungs were noted on other exams. Decreased pulmonary function was demonstrated by pulmonary function tests (forced expiratory volume in the first second, less than 80% of predicted value, 42.3%); hypoxemia (pO2 less than 80 mm Hg, 17.4%) and hypocalcemia (less than 8.5 mg/dl, 16.3%) were also noted. Ninety-four (10%) of the cases were hospitalized, and more than 83% of all cases were discharged with a primary diagnosis of HF exposure. There are several reports of individuals who are acutely and chronically exposed to HF; however, we are unaware of other published reports that describe exposure of a community to HF. This incident represented a unique opportunity to study the immediate health impact on a community of residents who were exposed to a hazardous materials release. Results of this analysis suggest that (a) initial health problems should be followed up, (b) any long-term health effects of HF exposure must be assessed, and (c) the health impact on the population at risk should be determined.

  8. Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.

    PubMed

    Lee, Byung-Hwan; Kim, Jisu; Lee, Ra Mi; Choi, Sun-Hye; Kim, Hyeon-Joong; Hwang, Sung-Hee; Lee, Myung Koo; Bae, Chun-Sik; Kim, Hyoung-Chun; Rhim, Hyewon; Lim, Kiwon; Nah, Seung-Yeol

    2016-01-26

    Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina. PMID:26706688

  9. Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome.

    PubMed

    Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

    2015-01-01

    Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid (HA) in the treatment of dry eyes using eye drops. In this paper, we present two methods to load HA in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. HA-laden hydrogel contact lenses prepared by soaking method showed release up to 48 h with acceptable physical and optical properties. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. HA entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to HA loading. The batch with 200-μg HA loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under the curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering HA through contact lenses for the treatment of dry eye syndrome. PMID:26176811

  10. Poly-(L-lactic acid) and citric acid-crosslinked gelatin composite matrices as a drug-eluting stent coating material with endothelialization, antithrombogenic, and drug release properties.

    PubMed

    Inoue, Motoki; Sasaki, Makoto; Katada, Yasuyuki; Fujiu, Katsuhito; Manabe, Ichiro; Nagai, Ryozo; Taguchi, Tetsushi

    2013-07-01

    Biodegradable composite matrices comprising poly-(L-lactic acid) (PLLA) and citric acid-crosslinked alkali-treated gelatin (AlGelatin) with endothelialization, antithrombogenic, and drug release properties were prepared. The characterization of composite matrices with various mixing ratios was performed by evaluating their swelling ratio, endothelial cell culture, antithrombogenic tests, and drug release behavior. Tamibarotene (Am80), which specifically inhibits smooth muscle cell proliferation, was employed as the drug. The swelling ratio of composite matrices decreased as the PLLA content decreased. The number of endothelial cells cultured on the surfaces of composite matrices was maximal at the PLLA/AlGelatin-TSC ratio of 80/20. Antithrombogenic tests revealed that the levels of platelets and fibrin network formation decreased as the AlGelatin-TSC content increased. The Am80 release test indicated that the release rate decreased as PLLA content increased. Using the resulting composite matrix, Am80-eluting stents possessing a smooth surface and a coating thickness of ∼15 μm were successfully obtained. Am80 was continuously released from the resulting stent at ∼40%, up to 28 days without burst release. Therefore, Am80-eluting stent with its antithrombogenic and endothelialization properties has great potential for clinical use. PMID:23280946

  11. Intracellular calcium-release and protein kinase C-activation stimulate sonic hedgehog gene expression during gastric acid secretion

    PubMed Central

    El-Zaatari, Mohamad; Zavros, Yana; Tessier, Art; Waghray, Meghna; Lentz, Steve; Gumucio, Deborah; Todisco, Andrea; Merchant, Juanita L.

    2010-01-01

    Introduction Hypochlorhydria during Helicobacter pylori infection inhibits gastric Shh expression. We investigated whether acid-secretory mechanisms regulate Shh gene expression through Ca2+i-dependent protein kinase C (PKC) or cAMP-dependent protein kinase A (PKA)-activation. Method We blocked Hedgehog signaling by transgenically overexpressing a secreted form of the Hedgehog interacting protein-1 (sHip-1), a natural inhibitor of hedgehog ligands, which induced hypochlorhydria. Gadolinium, EGTA+BAPTA, PKC-overexpressing adenoviruses, and PKC-inhibitors were used to modulate Ca2+i-release, PKC-activity and Shh gene expression in primary gastric cell, organ, and AGS cell line cultures. PKA hyperactivity was induced in the H+/K+-β-cholera-toxin overexpressing mice (Ctox). Results Mice that expressed sHip-1 had lower levels of gastric acid (hypochlorhydria), reduced production of somatostatin, and increased gastrin gene expression. Hypochlorhydria in these mice repressed Shh gene expression, similar to the levels obtained with omeprazole treatment of wild-type mice. However, Shh expression was also repressed in the hyperchlorhydric Ctox model with elevated cAMP, suggesting that the regulation of Shh was not solely acid-dependent, but pertained to specific acid-stimulatory signaling pathways. Based on previous reports that Ca2+i-release also stimulates acid secretion in parietal cells, we showed that gadolinium-, thapsigargin- and carbachol-mediated release of Ca2+i induced Shh expression. Ca2+-chelation with BAPTA+EGTA reduced Shh expression. Overexpression of PKC-α, -β and -δ (but not PKC-ε) induced Shh gene expression. In addition, phorbol esters induced a Shh-regulated reporter gene. Conclusion Secretagogues that stimulate gastric acid secretion induce Shh gene expression through increased Ca2+i-release and PKC activation. Shh might be the ligand transducing changes in gastric acidity to the regulation of G-cell secretion of gastrin. PMID:20816837

  12. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

    PubMed Central

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain

  13. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines.

    PubMed

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain

  14. Controlled release camptothecin tablets based on pluronic and poly(acrylic acid) copolymer. Effect of fabrication technique on drug stability, tablet structure, and release mode.

    PubMed

    Bromberg, Lev; Hatton, T Alan; Barreiro-Iglesias, Rafael; Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2007-06-01

    Poly(ethylene oxide)-b-poly(propylene oxide)-b-(polyethylene oxide)-g-poly(acrylic acid), a graft-comb copolymer of Pluronic 127 and poly(acrylic acid) (Pluronic-PAA), was explored as an excipient for tablet dosage form of camptothecin (CPT). The tablets were prepared by either direct compression of the drug-polymer physical blend, suspension in ethanol followed by evaporation, or compression after kneading and characterized with respect to their physical structures, drug stability, and release behavior. Porosity and water uptake rate were strongly dependent on the fabrication procedure, ranking in the order: direct compression of physical blend > compression after suspension/evaporation in ethanol > compression after kneading. Tablets prepared by compression of physical blends swelled in water with a rapid surface gel layer formation that impeded swelling and disintegration of the tablets core. These tablets were able to sustain the CPT release for a period of time longer than those observed with the tablets made by either suspension/evaporation or kneading, which disintegrated within a few minutes. Despite the tablet disintegration, the CPT release was impeded for at least 6 hr, which was attributed to the ability of the Pluronic-PAA copolymers to form micellar aggregates at the hydrated surface of the particles. Physical mixing did not alter the fraction of CPT being in the pharmaceutically active lactone form, whilst the preparation of the tablets by the other two methods caused a significant reduction in the lactone form content. Tablets prepared from the physical blends demonstrated CPT release rates increasing with the pH due to the PAA ionization leading to the increase in the rate and extent of the tablet swelling. The results obtained demonstrate the potential of the Pluronic-PAA copolymers for the oral administration of chemotherapeutic agents. PMID:17613025

  15. Lesions of nucleus accumbens affect morphine-induced release of ascorbic acid and GABA but not of glutamate in rats.

    PubMed

    Sun, Ji Y; Yang, Jing Y; Wang, Fang; Wang, Jian Y; Song, Wu; Su, Guang Y; Dong, Ying X; Wu, Chun F

    2011-10-01

    Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ-aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC-ECD) and fluorescent detection (HPLC-FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose-dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine-induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine-induced AA release may be mediated at least by µ-opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA-receptor mediated and synaptically localized in the NAc. PMID:20731632

  16. pH-responsive deoxyribonucleic acid capture/release by polydopamine functionalized magnetic nanoparticles.

    PubMed

    Wang, Yu; Ma, Xiangdong; Ding, Chun; Jia, Li

    2015-03-01

    Polydopamine functionalized magnetic nanoparticles (PDA@Fe3O4) were prepared and characterized by transmission electron microscopy, scanning electron microscopy, zeta potential and vibrating sample magnetometry. They were found to enable highly efficient capture of genomic deoxyribonucleic acid (DNA). The adsorption capacity of PDA@Fe3O4 for genomic DNA can reach 161 mg g(-1). The extraction protocol used aqueous solutions for DNA binding to and releasing from the surface of the magnetic particles based on the pH inducing the charge switch of amino and phenolic hydroxyl groups on PDA@Fe3O4. The extracted DNA with high quality (A260/A280=1.80) can be directly used as templates for polymerase chain reaction (PCR) followed by capillary electrophoresis (CE) analysis. None of the toxic chemical reagents and PCR inhibitors was used throughout the whole procedure. PDA@Fe3O4 based magnetic solid phase extraction (MSPE) method was superior to those using commercial kit and traditional phenol-chloroform extraction methods in yield of DNA. The developed PDA@Fe3O4 based MSPE-PCR-CE method was applied for simultaneous and fast detection of Listeria monocytogenes and Escherichia coli O157:H7 in milk. PMID:25682426

  17. Dynamic modeling of in vitro lipid digestion: individual fatty acid release and bioaccessibility kinetics.

    PubMed

    Giang, T M; Gaucel, S; Brestaz, P; Anton, M; Meynier, A; Trelea, I C; Le Feunteun, S

    2016-03-01

    The aim of this study was to gain knowledge about the role of triacylglycerol (TAG) composition in fatty acids (FA) of o/w emulsions on both the pancreatic lipolysis kinetics and the bioaccessibility of released products (i.e. contained within the bile salt micellar phase). A mathematical model was developed and its predictions were compared to a set of experimental data obtained during an in vitro digestion of a whey protein stabilized emulsion. Modeling results show that FA residues of TAG were hydrolyzed at specific rates, inducing different bioaccessibility kinetics. The estimated lipolysis rate constants of the studied FA (C8:0, C10:0≫C18:1 n-9≫C12:0>C14:0>C16:0≈C16:1 n-7>C22:6 n-3) were in close agreement with the available literature on the substrate specificity of pancreatic lipase. Results also suggest that lipolysis products are very rapidly solubilized in the bile salt mixed micelles with no fractionation according to the FA carbon chain. PMID:26471670

  18. Uptake and release of adrenal ascorbic acid in the guinea pig after injection of ACTH

    SciTech Connect

    Kipp, D.E.; Rivers, J.M.

    1987-09-01

    The effect of a single injection of ACTH (3 IU/100 g body weight) on the distribution of ascorbic acid (AA) and radiolabeled AA in 20 tissues was studied in adult male guinea pigs consuming 500 mg AA/kg diet. Saline- or ACTH-injected animals were simultaneously injected with (1-/sup 14/C)AA, and killed at 0.5, 1, 2, 4 and 6 h after injection. There was no significant difference between treatments in the weight of any tissue over the 6-h experimental period. As anticipated, the concentration of AA in the adrenals of animals injected with ACTH was 33% of that of animals injected with saline at 4 h. Unexpectedly, the concentration of radiolabeled AA in the adrenals at 0.5 h after ACTH injection was 172% of that after saline injection. The concentration of radiolabeled AA in the adrenal of the saline-injected animals increased slowly over time to reach a level similar to that of ACTH-injected animals by 6 h. There was no effect of ACTH on the level of AA or uptake in any of the other tissues examined. These results demonstrate that a single dose of ACTH markedly influences the retention of AA in the adrenal gland without similarly altering retention of AA in other tissues. Furthermore, ACTH treatment causes both accelerated uptake and release of AA into the adrenals.

  19. Release of FITC-BSA from poly(l-lactic acid) microspheres analysis using flow cytometry.

    PubMed

    Kuo, Chih-Feng; Tsao, Nina; Chou, Hsin-Hao; Liu, Yi-Ling; Hsieh, Wen-Chuan

    2012-01-01

    In this investigation, biodegradable polymer poly(L-lactic acid) (PLA) microspheres were prepared by the W(1)/O/W(2) solvent evaporation method. The inner phase was aqueous solution (W(1)) that contained bovine serum albumin that was labeled with fluorescein isothiocyanate (FITC-BSA). PLA was dissolved in chloroform with emulsifier sorbitan monooleate (span 80) as the dispersed phase (O). These two solutions (W(1)/O) were emulsified by a homogenizer to form a primary emulsion. Polyvinyl alcohol (PVA) used as surfactant, was applied in the formation of microspheres (W(2)). 0.5% (w/v) PLA was stirred at 3000 rpm using a homogenizer. Microspheres with sizes of up to around 10 μm were produced. These microspheres were separated by the glycerol gradient method, and take microspheres at part of 25% glycerol gradient concentration was analyzed by flow cytometry, indicating a more homogeneous particle size distribution than that not separated. The microspheres were degraded using several enzymes, and around 40% was degraded by 72 h. This result reveals the effectiveness of drug delivery by PLA microspheres, which was evaluated by performing a drug release test and flow cytometric analysis. The FITC-BSA concentration in the supernatant increased with the experimental time. At the phagocytosis experiments, encapsulated with FITC-BSA drug of microspheres can be used by the cell, as particle size approximately 1 μm. PMID:21992796

  20. The Salicylic Acid-Mediated Release of Plant Volatiles Affects the Host Choice of Bemisia tabaci

    PubMed Central

    Shi, Xiaobin; Chen, Gong; Tian, Lixia; Peng, Zhengke; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Zhou, Xuguo; Zhang, Youjun

    2016-01-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) causes serious crop losses worldwide by transmitting viruses. We have previously shown that salicylic acid (SA)-related plant defenses directly affect whiteflies. In this study, we applied exogenous SA to tomato plants in order to investigate the interaction between SA-induced plant volatiles and nonviruliferous B. tabaci B and Q or B- and Q-carrying tomato yellow leaf curl virus (TYLCV). The results showed that exogenous SA caused plants to repel nonviruliferous whiteflies, but the effect was reduced when the SA concentration was low and when the whiteflies were viruliferous. Exogenous SA increased the number and quantity of plant volatiles—especially the quantity of methyl salicylate and δ-limonene. In Y-tube olfactometer assays, methyl salicylate and δ-limonene repelled the whiteflies, but the repellency was reduced for viruliferous Q. We suggest that the release of plant volatiles as mediated by SA affects the interaction between whiteflies, plants, and viruses. Further studies are needed to determine why viruliferous Q is less sensitive than nonviruliferous Q to repellent plant volatiles. PMID:27376280

  1. The Salicylic Acid-Mediated Release of Plant Volatiles Affects the Host Choice of Bemisia tabaci.

    PubMed

    Shi, Xiaobin; Chen, Gong; Tian, Lixia; Peng, Zhengke; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Zhou, Xuguo; Zhang, Youjun

    2016-01-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) causes serious crop losses worldwide by transmitting viruses. We have previously shown that salicylic acid (SA)-related plant defenses directly affect whiteflies. In this study, we applied exogenous SA to tomato plants in order to investigate the interaction between SA-induced plant volatiles and nonviruliferous B. tabaci B and Q or B- and Q-carrying tomato yellow leaf curl virus (TYLCV). The results showed that exogenous SA caused plants to repel nonviruliferous whiteflies, but the effect was reduced when the SA concentration was low and when the whiteflies were viruliferous. Exogenous SA increased the number and quantity of plant volatiles-especially the quantity of methyl salicylate and δ-limonene. In Y-tube olfactometer assays, methyl salicylate and δ-limonene repelled the whiteflies, but the repellency was reduced for viruliferous Q. We suggest that the release of plant volatiles as mediated by SA affects the interaction between whiteflies, plants, and viruses. Further studies are needed to determine why viruliferous Q is less sensitive than nonviruliferous Q to repellent plant volatiles. PMID:27376280

  2. Hyaluronic Acid-Based Biocompatible Supramolecular Assembly for Sustained Release of Antiretroviral Drug.

    PubMed

    Song, Byeongwoon; Puskás, István; Szente, Lajos; Hildreth, James E K

    2016-09-01

    Human immunodeficiency virus (HIV) infection and its associated diseases continue to increase despite the progress in our understanding of HIV biology and the availability of a number of antiretroviral drugs. Adherence is a significant factor in the success of HIV therapy and current HIV treatment regimens require a combination of antiviral drugs to be taken at least daily for the remainder of a patient's life. A drug delivery system that allows sustained drug delivery could reduce the medical burden and costs associated with medication nonadherence. Here, we describe a novel supramolecular assembly or matrix that contains an anionic polymer hyaluronic acid, cationic polymer poly-l-lysine, and anionic oligosaccharide sulfobutylether-beta-cyclodextrin. HIV reverse transcriptase inhibitors Zidovudine and Lamivudine were successfully encapsulated into the polymer assembly in a noncovalent manner. The physicochemical properties and antiviral activity of the polymer assemblies were studied. The results of this study suggest that the supramolecular assemblies loaded with HIV drugs exert potent antiviral activity and allow sustained drug release. A novel drug delivery formulation such as the one described here could facilitate our efforts to reduce the morbidity and mortality associated with HIV infections and could be utilized in the design of therapeutic approaches for other diseases. PMID:26975245

  3. Macroporous chitosan hydrogels: Effects of sulfur on the loading and release behaviour of amino acid-based compounds.

    PubMed

    Elviri, Lisa; Asadzadeh, Maliheh; Cucinelli, Roberta; Bianchera, Annalisa; Bettini, Ruggero

    2015-11-01

    Chitosan is a biodegradable, biocompatible polymer of natural origin widely applied to the preparation of functional hydrogels suitable for controlled release of drugs, peptides and proteins. Non-covalent interactions, expecially ionic interactions, are the main driver of the loading and release behaviour of amino acids or peptides from chitosan hydrogels. With the aim to improve the understanding of the mechanisms governing the behaviour of chitosan hydrogels on peptide uptake and delivery, in this paper the attention was focused on the role played by sulfur on the interactions of chitosan hydrogels with sulfur-containing amino acids (AA) and peptides. Hence, loading and release experiments on cysteine, cystine and glutathione (SH containing amino acid, dipeptide and tripeptide, respectively) as well as on glycine and valine as apolar amino acids were carried out. For these puroses, chitosan hydrogels were prepared in an easy and reproducible manner by a freeze-gelation process on a poly-L-lysine coated support. The hydrogel surface pore size, uniformity and distribution were tested. Optimal results (D50 = 26 ± 4 μm) were obtained by using the poly-L-lysine positively-charged surface. The loading results gathered evidenced that the sulfur-containing molecules presented an increased absorption both in terms of rate and extent by chitosan hydrogels with respect to nonpolar amino acids, mainly due to ionic and hydrogen bond interactions. ATR-FTIR analysis carried out on chitosan hydrogels, with and without the AA related compounds to study putative interactions, supported these apparent sulfur-dependent results. Finally, chitosan hydrogels displayed excellent retention capabilities (AA release <5%) for all AA, strongly supporting the use of chitosan hydrogels as matrix for controlled drug release. PMID:26256323

  4. Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.

    PubMed

    Kim, Kyung Soo; Jin, Sung Giu; Mustapha, Omer; Yousaf, Abid Mehmood; Kim, Dong Wuk; Kim, Young Hun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2015-07-25

    The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product. PMID:26024820

  5. Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.

    PubMed

    Zhang, Wuxia; Dong, Dongqi; Li, Peng; Wang, Dongdong; Mu, Haibo; Niu, Hong; Duan, Jinyou

    2016-03-30

    Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability. PMID:26794949

  6. Estimating industrial and domestic environmental releases of perfluorooctanoic acid and its salts in China from 2004 to 2012.

    PubMed

    Li, Li; Zhai, Zihan; Liu, Jianguo; Hu, Jianxin

    2015-06-01

    China has been documented as one of the few remaining producers of perfluorooctanoic acid and its salts (PFOA/PFO) and the world's major contamination hotspot. However, limited information has been available for evaluating their environmental releases in China and the contribution to global PFOA/PFO burden. Here we present the first source-specific inventory for environmental releases of PFOA/PFO in China from 2004 to 2012, using a bottom-up approach for industrial sources and an inverse approach for domestic sources. Our results show that China became the current world's largest PFOA/PFO emitter, with cumulative environmental releases reaching 250tonnes (t) over the period of nine years. The eastern region was identified as the hotspot of environmental releases. Most of the national environmental releases were due to the activities of the fluorochemical industry (94.0%) rather than domestic use of PFOA/PFO-related consumer products (6.0%). Fluoropolymer manufacturing and processing, a dominating industrial source, contributed 83.7% of the national environmental releases. In contrast to the general decline trends in annual industrial environmental releases of PFOA/PFO in most industrialized countries, the trend increased in China because of the expansion of production as a result of the global geographical transition in fluorochemical industry. Based on these results, we recommend that the future reduction options are required in industrial sector in China. PMID:25541533

  7. Serotonin stimulates phospholipase A sub 2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis

    SciTech Connect

    Felder, C.C.; Ma, A.L.; Axelrod, J.; Kanterman, R.Y. )

    1990-03-01

    Serotonin (5-HT) stimulated the release of arachidonic acid in hippocampal neurons cocultured with glial cells but not in glial cultures alone. Similar results were observed for the 5-HT-stimulated release of inositol phosphates. These results suggest a neural but not glial origin of both responses. Pharmacological studies suggested that release of arachidonic acid and inositol phosphates was mediated by a type 2 5-HTT (5-HT{sub 2}) receptor. 5-HT-stimulated release of arachidonic acid was also detected in cortical neurons, which contain high levels of 5-HT{sub 2} receptors, but not striatum, spinal cord, or cerebellar granule cells, which have very low levels or are devoid of 5-HT{sub 2} receptors. The phorbol ester phorbol 12-myristate 13-acetate augmented the 5-HT-stimulated release of arachidonic acid but inhibited the 5-HT-stimulated release of inositol phosphates. 5-HT-stimulated release of arachidonic acid, but not inositol phosphates, was dependent on extracellular calcium. 5-HT stimulated the release of ({sup 3}H)lysophosphatidylcholine from ({sup 3}H)choline-labeled cells with no increase in the release of ({sup 3}H)choline or phospho({sup 3}H)choline. These data suggest that 5-HT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A{sub 2}, independent of the activation of phospholipase C.

  8. Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis.

    PubMed Central

    Felder, C C; Kanterman, R Y; Ma, A L; Axelrod, J

    1990-01-01

    Serotonin (5-HT) stimulated the release of arachidonic acid in hippocampal neurons cocultured with glial cells but not in glial cultures alone. Similar results were observed for the 5-HT-stimulated release of inositol phosphates. These results suggest a neural but not glial origin of both responses. Pharmacological studies suggested that release of arachidonic acid and inositol phosphates was mediated by a type 2 5-HT (5-HT2) receptor. 5-HT-stimulated release of arachidonic acid was also detected in cortical neurons, which contain high levels of 5-HT2 receptors, but not striatum, spinal cord, or cerebellar granule cells, which have very low levels or are devoid of 5-HT2 receptors. The phorbol ester phorbol 12-myristate 13-acetate augmented the 5-HT-stimulated release of arachidonic acid but inhibited the 5-HT-stimulated release of inositol phosphates. 5-HT-stimulated release of arachidonic acid, but not inositol phosphates, was dependent on extracellular calcium. 5-HT stimulated the release of [3H]lysophosphatidylcholine from [3H]choline-labeled cells with no increase in the release of [3H]choline or phospho[3H]choline. These data suggest that 5-HT stimulated the release of arachidonic acid in hippocampal neurons through the activation of phospholipase A2, independent of the activation of phospholipase C. PMID:2315313

  9. Ascorbic acid does not modulate stimulated dopamine release: in vivo voltammetric data in the rat.

    PubMed

    Stamford, J A; Kruk, Z L; Millar, J

    1985-10-10

    Electrical stimulation of the nigrostriatal pathway released dopamine (DA) in the striatum of the anaesthetized rat. The level of DA released by 10-s stimulus trains was measured by high-speed cyclic voltammetry. Metoclopramide (10 mg/kg) increased DA release by approximately 20%. Apomorphine (1.76 mg/kg) caused a approximately 40% decrease in release which was blocked by metoclopramide. Ascorbate (1.76 g/kg) had no effect on stimulated DA release. Furthermore, pretreatment of rats with ascorbate trebled the striatal extracellular ascorbate level, but failed to modify the effects of metoclopramide and apomorphine on DA release. We conclude that ascorbate has no effect on the presynaptic autoreceptors that modulate striatal DA release in vivo. PMID:2999651

  10. Rapid Trimming of Cell Surface Polysialic Acid (PolySia) by Exovesicular Sialidase Triggers Release of Preexisting Surface Neurotrophin.

    PubMed

    Sumida, Mizuki; Hane, Masaya; Yabe, Uichiro; Shimoda, Yasushi; Pearce, Oliver M T; Kiso, Makoto; Miyagi, Taeko; Sawada, Makoto; Varki, Ajit; Kitajima, Ken; Sato, Chihiro

    2015-05-22

    As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac (N-acetylneuraminic acid), was demonstrated. PolySia is known to modulate cell adhesion, migration, and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc (N-glycolylneuraminic acid) caused resistance to Neu1-induced polySia turnover and also inhibited the associated release of brain-derived neurotrophic factor. These results indicate the importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases in neurotrophin regulation. PMID:25750127

  11. Uronic Acid products release from enzymically active cell wall from tomato fruit and its dependency on enzyme quantity and distribution.

    PubMed

    Huber, D J; Lee, J H

    1988-07-01

    Isolated cell wall from tomato (Lycopersicon esculentum Mill. cv Rutgers) fruit released polymeric (degree of polymerization [DP] > 8), oligomeric, and monomeric uronic acids in a reaction mediated by bound polygalacturonase (PG) (EC 3.2.1.15). Wall autolytic capacity increased with ripening, reflecting increased levels of bound PG; however, characteristic oligomeric and monomeric products were recovered from all wall isolates exhibiting net pectin release. The capacity of wall from fruit at early ripening (breaker, turning) to generate oligomeric and monomeric uronic acids was attributed to the nonuniform ripening pattern of the tomato fruit and, consequently, a locally dense distribution of enzyme in wall originating from those fruit portions at more temporally advanced stages of ripening. Artificial autolytically active wall, prepared by permitting solubilized PG to bind to enzymically inactive wall from maturegreen fruit, released products which were similar in size characteristics to those recovered from active wall isolates. Extraction of wall-bound PG using high concentrations of NaCl (1.2 molar) did not attenuate subsequent autolytic activity but greatly suppressed the production of oligomeric and monomeric products. An examination of water-soluble uronic acids recovered from ripe pericarp tissue disclosed the presence of polymeric and monomeric uronic acids but only trace quantities of oligomers. The significance in autolytic reactions of enzyme quantity and distribution and their possible relevance to in vivo pectin degradation will be discussed. PMID:16666191

  12. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid.

    PubMed

    Duncan, Sylvia H; Russell, Wendy R; Quartieri, Andrea; Rossi, Maddalena; Parkhill, Julian; Walker, Alan W; Flint, Harry J

    2016-07-01

    Cereal fibres such as wheat bran are considered to offer human health benefits via their impact on the intestinal microbiota. We show here by 16S rRNA gene-based community analysis that providing amylase-pretreated wheat bran as the sole added energy source to human intestinal microbial communities in anaerobic fermentors leads to the selective and progressive enrichment of a small number of bacterial species. In particular, OTUs corresponding to uncultured Lachnospiraceae (Firmicutes) related to Eubacterium xylanophilum and Butyrivibrio spp. were strongly enriched (by five to 160 fold) over 48 h in four independent experiments performed with different faecal inocula, while nine other Firmicutes OTUs showed > 5-fold enrichment in at least one experiment. Ferulic acid was released from the wheat bran during degradation but was rapidly converted to phenylpropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites that are detected in human faecal samples. Pure culture work using bacterial isolates related to the enriched OTUs, including several butyrate-producers, demonstrated that the strains caused substrate weight loss and released ferulic acid, but with limited further conversion. We conclude that breakdown of wheat bran involves specialist primary degraders while the conversion of released ferulic acid is likely to involve a multi-species pathway. PMID:26636660

  13. Wheat bran promotes enrichment within the human colonic microbiota of butyrate‐producing bacteria that release ferulic acid

    PubMed Central

    Duncan, Sylvia H.; Russell, Wendy R.; Quartieri, Andrea; Rossi, Maddalena; Parkhill, Julian; Flint, Harry J.

    2016-01-01

    Summary Cereal fibres such as wheat bran are considered to offer human health benefits via their impact on the intestinal microbiota. We show here by 16S rRNA gene‐based community analysis that providing amylase‐pretreated wheat bran as the sole added energy source to human intestinal microbial communities in anaerobic fermentors leads to the selective and progressive enrichment of a small number of bacterial species. In particular, OTUs corresponding to uncultured Lachnospiraceae (Firmicutes) related to E ubacterium xylanophilum and B utyrivibrio spp. were strongly enriched (by five to 160 fold) over 48 h in four independent experiments performed with different faecal inocula, while nine other Firmicutes OTUs showed > 5‐fold enrichment in at least one experiment. Ferulic acid was released from the wheat bran during degradation but was rapidly converted to phenylpropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites that are detected in human faecal samples. Pure culture work using bacterial isolates related to the enriched OTUs, including several butyrate‐producers, demonstrated that the strains caused substrate weight loss and released ferulic acid, but with limited further conversion. We conclude that breakdown of wheat bran involves specialist primary degraders while the conversion of released ferulic acid is likely to involve a multi‐species pathway. PMID:26636660

  14. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    von Sperber, C.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-07-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (myo-inositol hexakisphosphate, IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields available Pi and less phosphorylated inositol derivates as products. The hydrolysis of organic P compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'-monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as a substrate were prepared. During the hydrolysis of IP6 by phytase, four of the six Pi were released, and one oxygen atom from water was incorporated into each Pi. This incorporation of oxygen from water into Pi was subject to an apparent inverse isotopic fractionation (ϵ ~ 6 to 10 ‰), which was similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ~ 7 ‰), where less than three Pi were released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ~ -12 ‰), similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ϵ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking

  15. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    Sperber, C. v.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-03-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields plant available inorganic phosphate (Pi) and less phosphorylated inositol derivates as products. The hydrolysis of organic P-compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as substrate were prepared. During the hydrolysis of IP6 by phytase, four Pi are released, and one oxygen atom from water is incorporated into each Pi. This incorporation of oxygen from water into Pi is subject to an apparent inverse isotopic fractionation (ϵ ∼ 6 to 10‰), which is similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ∼ 7‰) where less than three Pi are released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ∼ -12‰), again similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ɛ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking substrate-dependency of

  16. Controlled-release fertilizer prepared using a biodegradable aliphatic copolyester of poly(butylene succinate) and dimerized fatty acid.

    PubMed

    Lubkowski, Krzysztof; Smorowska, Aleksandra; Grzmil, Barbara; Kozłowska, Agnieszka

    2015-03-18

    The preparation and characterization of a controlled-release multicomponent (NPK) fertilizer with the coating layer consisting of a biodegradable copolymer of poly(butylene succinate) and a butylene ester of dilinoleic acid (PBS/DLA) is reported. The morphology and structure of the resulting polymer-coated materials and the thickness of the covering layers were examined using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis. The mechanical properties of these materials were determined with a strength-testing machine. Nutrient release was measured in water using spectrophotometry, potentiometry, and conductivity methods. The results of the nutrient release experiments from these polymer-coated materials were compared with the requirements for controlled-release fertilizers. A conceptual model is presented describing the mechanism of nutrient release from the materials prepared in this study. This model is based on the concentrations of mineral components inside the water-penetrated fertilizer granules, the diffusion properties of the nutrients in water, and a diffusion coefficient through the polymer layer. The experimental kinetic data on nutrient release were interpreted using the sigmoidal model equation developed in this study. PMID:25715823

  17. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids

    PubMed Central

    Knöös, Patrik

    2015-01-01

    A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. PMID:26473964

  18. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.

    PubMed

    Knöös, Patrik; Svensson, Anna V; Ulvenlund, Stefan; Wahlgren, Marie

    2015-01-01

    A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. PMID:26473964

  19. Antioxidant modulation of oxidant-stimulated uptake and release of arachidonic acid in eicosapentaenoic acid-supplemented human lymphoma U937 cells.

    PubMed

    Obajimi, Oluwakemi; Black, Kenneth D; Glen, Iain; Ross, Brian M

    2007-02-01

    Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as treatments for a variety of medical conditions. PUFA supplementation can, however, result in increased oxidative stress causing elevated turnover rate of membrane phospholipids, impairment of membrane integrity and increased formation of inflammatory mediators. The aim of this study was to determine which antioxidant compounds were most effective in ameliorating the stimulation of phospholipid turnover by oxidative stress. U937 cells were supplemented with eicosapentaenoic acid and either ascorbic acid, alpha-tocopherol, beta-carotene or astaxanthin prior to being challenged with oxidant. Although all antioxidants were found to be effective in decreasing oxidant-stimulated peroxide formation, only alpha-tocopherol significantly decreased oxidant-stimulated release of 3H-labeled arachidonic acid (AA), while ascorbic acid markedly increased release. All antioxidants except alpha-tocopherol decreased oxidant-stimulated 3H-AA uptake. Our data suggest that antioxidants are not equally effective in combating the effects of oxidative stress upon membrane phospholipid turnover, and that optimal protection will require mixtures of antioxidants. PMID:17198751

  20. Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

    PubMed

    Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

    2016-11-15

    The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. PMID:27450331

  1. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    PubMed

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent. PMID:10934737

  2. Drying of micro-encapsulated lactic acid bacteria — Effects of trehalose and immobilization on cell survival and release properties

    NASA Astrophysics Data System (ADS)

    Li, Xiaoyan; Chen, Xiguang

    2009-03-01

    Lactic acid bacteria (LAB) were encapsulated with alginate, gelatin and trehalose additives by the extrusion method and dried at 4 °C. The microcapsules were generally spherical and had a wrinkled surface with a size of 1.7 mm ± 0.2 mm. Trehalose as a carbohydrate source in the culture medium could reduce acid production and performed no function in the positive proliferation of LAB. Using trehalose as a carbohydrate source and protective medium simultaneously had a benefit in the protection of LAB cells during the storage at 4 °C. The density of live LAB cells could be 107 CFU g-1 after 8 weeks of storage. Cells of LAB could be continuously released from the capsules from the acidic (pH 1.2) to neutral conditions (pH 6.8). The release amounts and proliferation speeds of LAB cells in neutral medium were much larger and faster than those in acidic conditions. Additionally, immobilization of LAB could improve the survival of cells when they were exposed to acidic medium (pH 1.2) with a survival rate of 76 %.

  3. Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor.

    PubMed

    Huang, Pingsheng; Song, Huijuan; Wang, Weiwei; Sun, Yu; Zhou, Junhui; Wang, Xue; Liu, Jinjian; Liu, Jianfeng; Kong, Deling; Dong, Anjie

    2014-08-11

    Reasonably structural design of nanoparticles (NPs) to combine functions of prolonged systemic circulation, enhanced tumor targeting and specific intracellular drug release is crucial for antitumor drug delivery. Combining advantages of Arg-Gly-Asp (RGD) for active tumor targeting, zwitterionic polycarboxybetaine methacrylate (PCB) for prolonged systemic circulation, poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) for acid-triggered intracellular release, novel RGD-PCB-b-PDPA (RGD-PCD) block copolymers were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and followed by functionalization with RGD. Doxorubicine (DOX) was encapsulated within the RGD-PCD NPs as model medicine (RGD-PCD/DOX NPs). With ultra pH-sensitivity of PDPA, the drug release was restrained at pH 7.4 for only 24% within 36 h, which was increased to 60% at pH 6.0 within 24 h, and released more rapidly at pH 5.0 for 100% within 5 h, indicating that the RGD-PCD/DOX NPs were able to turn drug release "off" at neutral pH (e.g., systemic circulation) whereas "on" under acidic conditions (e.g., inside endo/lysosomes). Furthermore, the results of fluorescence microscopy and flow cytometry analysis demonstrated improved internalization of RGD-PCD/DOX NPs in HepG2 cells via integrin-mediated endocytosis with rapid DOX release intracellularly. Consequently, the RGD-PCD/DOX NPs showed considerable cytotoxicity against HepG2 and HeLa cells in comparison with free DOX. Importantly, the RGD-PCD/DOX NPs exhibited little protein adsorption property with excellent serum stability, which led to prolonged systemic circulation and enhanced tumor accumulation in tumor-bearing nude mice. Therefore, this multifunctional RGD-PCD NPs, which represented the flexible design approach, showed great potential for the development of novel nanocarriers in tumor-targeted drug delivery. PMID:25054812

  4. A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release.

    PubMed

    Gong, Chu; Shan, Meng; Li, Bingqiang; Wu, Guolin

    2016-10-01

    A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release. PMID:27388968

  5. Preparation of polyelectrolyte complex nanoparticles of chitosan and poly(2-acry1amido-2-methylpropanesulfonic acid) for doxorubicin release.

    PubMed

    Zhang, Liping; Wang, Jie; Ni, Caihua; Zhang, Yanan; Shi, Gang

    2016-01-01

    A new kind of polyelectrolyte complex (PEC) based on cationic chitosan (CS) and anionic poly(2-acry1amido-2-methylpropanesulfonic acid) (PAMPS) was prepared using a polymer-monomer pair reaction system. Chitosan was mixed with 2-acry1amido-2-methylpropanesulfonic acid) (AMPS) in an aqueous solution, followed by polymerization of AMPS. The complex was formed by electrostatic interaction of NH3(+) groups of CS and SO3(-) groups of AMPS, leading to a formation of complex nanoparticles of CS-PAMPS. A series of nanoparticles were obtained by changing the weight ratio of CS to AMPS, the structure and properties of nanoparticles were investigated. It was observed that the nanoparticles possessed spherical morphologies with average diameters from 255 nm to 390 nm varied with compositions of the nanoparticles. The nanoparticles were used as drug vehicles for doxorubicin, displaying relative high drug loading rate and encapsulation rate. The vitro release profiles revealed that the drug release could be controlled by adjusting pH of the release media. The nanoparticles demonstrated apparent advantages such as simple preparation process, free of organic solvents, size controllable, good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field. PMID:26478364

  6. Acid-independent release of secretin and cholecystokinin by intraduodenal infusion of fat in humans.

    PubMed

    Rhodes, R A; Skerven, G; Chey, W Y; Chang, T M

    1988-01-01

    In order to clarify a possible role of fat content in the release of secretin and cholecystokinin by liquid nutritional supplements in humans, duodenal pH and plasma concentrations of secretin and cholecystokinin were studied during the intraduodenal infusion of Ensure, Vivonex, 10% Intralipid, and sodium oleate. Significant release of secretin was observed with Intralipid and sodium oleate, while significant release of cholecystokinin was observed with all four testing solutions. Duodenal pH was rarely below 4.5 during the infusion of Ensure, Intralipid, and sodium oleate. Duodenal pH was high, greater than 6.0, when plasma secretin and cholecystokinin levels were elevated during the administration of Ensure, Intralipid, and sodium oleate. We conclude that both secretin and cholecystokinin are released in response to fat solutions in the duodenum and that low duodenal pH was not responsible for either secretin or cholecystokinin release during intraduodenal infusions of Ensure, Intralipid, or sodium oleate. PMID:3140233

  7. Extracellular ATP stimulates exocytosis via localized Ca(2+) release from acidic stores in rat pancreatic beta cells.

    PubMed

    Xie, Li; Zhang, Ming; Zhou, Wei; Wu, Zhengxing; Ding, Jiuping; Chen, Liangyi; Xu, Tao

    2006-04-01

    Three different methods, membrane capacitance (C(m)) measurement, amperometry and FM dye labeling were used to investigate the role of extracellular ATP in insulin secretion from rat pancreatic beta cells. We found that extracellular application of ATP mobilized intracellular Ca(2+) stores and synchronously triggered vigorous exocytosis. No influence of ATP on the readily releasable pool of vesicles was observed, which argues against a direct modulation of the secretory machinery at a level downstream of Ca(2+) elevation. The stimulatory effects of ATP were greatly reduced by intracellular perfusion of BAPTA but not EGTA, suggesting a close spatial association of fusion sites with intracellular Ca(2+) releasing sites. ATP-induced Ca(2+) transients and exocytosis were not blocked by thapsigargin (TG), by a ryanodine receptor antagonist or by dissipation of pH in acidic stores by monensin alone, but they were greatly attenuated by IP(3) receptor inhibition as well as ionomycin plus monensin, suggesting involvement of IP(3)-sensitive acidic Ca(2+) stores. Taken together, our data suggest that extracellular ATP triggers exocytosis by mobilizing spatially limited acidic Ca(2+) stores through IP(3) receptors. This mechanism may explain how insulin secretion from the pancreas is coordinated through diffusible ATP that is co-released with insulin. PMID:16536741

  8. Nicotinic Acid Adenine Dinucleotide Phosphate Analogs Substituted on the Nicotinic Acid and Adenine Ribosides. Effects on Receptor-Mediated Ca2+ release

    PubMed Central

    Trabbic, Christopher J.; Zhang, Fan; Walseth, Timothy F.; Slama, James T.

    2015-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the nicotinic acid 5-position are recognized by the sea urchin receptor, albeit with a 20–500 fold loss in agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release Ca2+ with an EC50 of 31 µM and to compete with NAADP for receptor binding with an IC50 of 56 nM. Attachment of charged groups to the nicotinic acid of NAADP is associated with loss of activity, suggesting that the nicotinate riboside moiety is recognized as a neutral zwitterion. Substituents (Br- and N3-) can be introduced at the 8-adenosyl position of NAADP while preserving high potency and agonist efficacy and an NAADP derivative substituted at both the 5-position of the nicotinic acid and at the 8-adenosyl position was also recognized although the agonist potency was significantly reduced. PMID:25826221

  9. Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and nitric oxide releasing investigations.

    PubMed

    Griffith, Darren; Krot, Krystyna; Comiskey, Jedd; Nolan, Kevin B; Marmion, Celine J

    2008-01-01

    The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru(III) involves initial formation of Ru(III)-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru(III)-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids. PMID:18399240

  10. Direct behavioral evidence that unique bile acids released by larval sea lamprey (Petromyzon marinus) function as a migratory pheromone

    USGS Publications Warehouse

    Bjerselius, R.; Li, W.; Teeter, J.H.; Seelye, J.G.; Johnsen, P.B.; Maniak, P.J.; Grant, G.C.; Polkinghorne, C.N.; Sorensen, P.W.

    2000-01-01

    Four behavioral experiments conducted in both the laboratory and the field provide evidence that adult sea lamprey (Petromyzon marinus) select spawning rivers based on the odor of larvae that they contain and that bile acids released by the larvae are part of this pheromonal odor. First, when tested in a recirculating maze, migratory adult lamprey spent more time in water scented with larvae. However, when fully mature, adults lost their responsiveness to larvae and preferred instead the odor of mature individuals. Second, when tested in a flowing stream, migratory adults swam upstream more actively when the water was scented with larvae. Third, when migratory adults were tested in a laboratory maze containing still water, they exhibited enhanced swimming activity in the presence of a 0.1 nM concentration of the two unique bile acids released by larvae and detected by adult lamprey. Fourth, when adults were exposed to this bile acid mixture within flowing waters, they actively swam into it. Taken together, these data suggest that adult lamprey use a bile acid based larval pheromone to help them locate spawning rivers and that responsiveness to this cue is influenced by current flow, maturity, and time of day. Although the precise identity and function of the larval pheromone remain to be fully elucidated, we believe that this cue will ultimately prove useful as an attractant in sea lamprey control.

  11. Caffeic Acid Phenethyl Ester: Consequences of Its Hydrophobicity in the Oxidative Functions and Cytokine Release by Leukocytes

    PubMed Central

    Paracatu, Luana Chiquetto; Faria, Carolina Maria Quinello Gomes; Rennó, Camila; Palmeira, Patricia; da Fonseca, Luiz Marcos; Ximenes, Valdecir Farias

    2014-01-01

    Numerous anti-inflammatory properties have been attributed to caffeic acid phenethyl ester (CAPE), an active component of propolis. NADPH oxidases are multienzymatic complexes involved in many inflammatory diseases. Here, we studied the importance of the CAPE hydrophobicity on cell-free antioxidant capacity, inhibition of the NADPH oxidase and hypochlorous acid production, and release of TNF-α and IL-10 by activated leukocytes. The comparison was made with the related, but less hydrophobic, caffeic and chlorogenic acids. Cell-free studies such as superoxide anion scavenging assay, triene degradation, and anodic peak potential (Epa) measurements showed that the alterations in the hydrophobicity did not provoke significant changes in the oxidation potential and antiradical potency of the tested compounds. However, only CAPE was able to inhibit the production of superoxide anion by activated leukocytes. The inhibition of the NADPH oxidase resulted in the blockage of production of hypochlorous acid. Similarly, CAPE was the more effective inhibitor of the release of TNF-α and IL-10 by Staphylococcus aureus stimulated cells. In conclusion, the presence of the catechol moiety and the higher hydrophobicity were essential for the biological effects. Considering the involvement of NADPH oxidases in the genesis and progression of inflammatory diseases, CAPE should be considered as a promising anti-inflammatory drug. PMID:25254058

  12. Host-Pathogen interactions. 25. Endopolygalacturonic acid lyase from Erwinia carotovora elicits phytoalexin accumulation by releasing plant cell wall fragments

    SciTech Connect

    Davis, K.R.; Lyon, G.D.; Darvill, A.G.; Albersheim, P.

    1984-01-01

    Heat-labile elicitors of phytoalexin accumulation in soybeans (Glycine max L. Merr. cv Wayne) were detected in culture filtrates of Erwinia carotovora grown on a defined medium containing citrus pectin as the sole carbon source. The heat-labile elicitors were highly purified by cation-exchange chromatography on a CM-Sephadex (C-50) column, followed by agarose-affinity chromatography on a Bio-Gel A-0.5m gel filtration column. The heat-labile elicitor activity co-purified with two ..cap alpha..-1,4-endopolygalacturonic acid lyases (EC 4 x 2 x 2 x 2). Endopolygalacturonic acid lyase activity appeared to be necessary for elicitor activity because heat-inactivated enzyme preparations did not elicit phytoalexins. The purified endopolygalacturonic acid lyases elicited pterocarpan phytoalexins at microbial-inhibitory concentrations in the soybean-cotyledon bioassay when applied at a concentration of 55 nanograms per milliliter (1 x 10/sup -9/ molar). One of these lyases released heat-stable elicitors from soybean cell walls, citrus pectin, and sodium polypectate. The heat-stable elicitor-active material solubilized from soybean cell walls by the lyase was composed of at least 90% (w/v) uronosyl residues. These results demonstrate that endopolygalacturonic acid lyase elicits phytoalexin accumulation by releasing fragments from pectic polysaccharides in plant cell walls.

  13. Madhucosides A and B, protobassic acid glycosides from Madhuca indica with inhibitory activity on free radical release from phagocytes.

    PubMed

    Pawar, Rahul S; Bhutani, K K

    2004-04-01

    The structures of madhucosides A (1) and B (2), isolated from the bark of Madhuca indica, were established as 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1--> 3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid and 3-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranosyl-28-O-[beta-D-xylopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->4)]-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl]protobassic acid, respectively. These two compounds showed significant inhibitory effects on both superoxide release from polymorphonuclear cells in a NBT reduction assay and hypochlorous acid generation from neutrophils assessed in a luminol-enhanced chemiluminescence assay. PMID:15104500

  14. Purified group X secretory phospholipase A(2) induced prominent release of arachidonic acid from human myeloid leukemia cells.

    PubMed

    Hanasaki, K; Ono, T; Saiga, A; Morioka, Y; Ikeda, M; Kawamoto, K; Higashino, K; Nakano, K; Yamada, K; Ishizaki, J; Arita, H

    1999-11-26

    Group X secretory phospholipase A(2) (sPLA(2)-X) possesses several structural features characteristic of both group IB and IIA sPLA(2)s (sPLA(2)-IB and -IIA) and is postulated to be involved in inflammatory responses owing to its restricted expression in the spleen and thymus. Here, we report the purification of human recombinant COOH-terminal His-tagged sPLA(2)-X, the preparation of its antibody, and the purification of native sPLA(2)-X. The affinity-purified sPLA(2)-X protein migrated as various molecular species of 13-18 kDa on SDS-polyacrylamide gels, and N-glycosidase F treatment caused shifts to the 13- and 14-kDa bands. NH(2)-terminal amino acid sequencing analysis revealed that the 13-kDa form is a putative mature sPLA(2)-X and the 14-kDa protein possesses a propeptide of 11 amino acid residues attached at the NH(2) termini of the mature protein. Separation with reverse-phase high performance liquid chromatography revealed that N-linked carbohydrates are not required for the enzymatic activity and pro-sPLA(2)-X has a relatively weak potency compared with the mature protein. The mature sPLA(2)-X induced the release of arachidonic acid from phosphatidylcholine more efficiently than other human sPLA(2) groups (IB, IIA, IID, and V) and elicited a prompt and marked release of arachidonic acid from human monocytic THP-1 cells compared with sPLA(2)-IB and -IIA with concomitant production of prostaglandin E(2). A prominent release of arachidonic acid was also observed in sPLA(2)-X-treated human U937 and HL60 cells. Immunohistochemical analysis of human lung preparations revealed its expression in alveolar epithelial cells. These results indicate that human sPLA(2)-X is a unique N-glycosylated sPLA(2) that releases arachidonic acid from human myeloid leukemia cells more efficiently than sPLA(2)-IB and -IIA. PMID:10567392

  15. NMR studies reveal the role of biomembranes in modulating ligand binding and release by intracellular bile acid binding proteins.

    PubMed

    Pedò, Massimo; Löhr, Frank; D'Onofrio, Mariapina; Assfalg, Michael; Dötsch, Volker; Molinari, Henriette

    2009-12-18

    Bile acid molecules are transferred vectorially between basolateral and apical membranes of hepatocytes and enterocytes in the context of the enterohepatic circulation, a process regulating whole body lipid homeostasis. This work addresses the role of the cytosolic lipid binding proteins in the intracellular transfer of bile acids between different membrane compartments. We present nuclear magnetic resonance (NMR) data describing the ternary system composed of the bile acid binding protein, bile acids, and membrane mimetic systems, such as anionic liposomes. This work provides evidence that the investigated liver bile acid binding protein undergoes association with the anionic membrane and binding-induced partial unfolding. The addition of the physiological ligand to the protein-liposome mixture is capable of modulating this interaction, shifting the equilibrium towards the free folded holo protein. An ensemble of NMR titration experiments, based on nitrogen-15 protein and ligand observation, confirm that the membrane and the ligand establish competing binding equilibria, modulating the cytoplasmic permeability of bile acids. These results support a mechanism of ligand binding and release controlled by the onset of a bile salt concentration gradient within the polarized cell. The location of a specific protein region interacting with liposomes is highlighted. PMID:19836400

  16. Influence of organic acids on kinetic release of chromium in soil contaminated with leather factory waste in the presence of some adsorbents.

    PubMed

    Taghipour, Marzieh; Jalali, Mohsen

    2016-07-01

    In this study, batch experiments were conducted to investigate the effects of nanoparticles (NPs) (MgO, ZnO, TiO2) and clay minerals (bentonite, zeolite) on the release of chromium (Cr) from leather factory waste (LFW) and LFW treated soil using organic acids. Chromium release from all treatments was studied in the presence of citric acid, oxalic acid and CaCl2 solutions. The results showed that, in all treatments, organic acids released more Cr than inorganic salt (CaCl2). The release of Cr by citric acid was higher than that by oxalic acid. In LFW treated soil and LFW, the release of Cr from the all treatments with NPs was less than that from the clay mineral treatments. On the other hand, in the presence of organic acids, Cr release by NPs and clay minerals decreased. Two kinetic models including pseudo-first- and pseudo-second-order model were tested to describe the time dependent Cr release data. Among the kinetic models used, the pseudo-second-order model generally gave the best fits to experimental data. Before and after release experiments, Cr in LFW, treated LFW, control soil and LFW treated soils were fractionated. In all treatments, the greatest amounts of Cr were found in the residual fraction (RES). The organic acids were effective in reducing the exchangeable (EXC), bound to organic matter (OM) and bound to carbonate (CAR) fractions of Cr in all treatments, whereas, after release of Cr from treated soils, Cr remained mainly in the RES fraction. The application of NPs and clay minerals in soil led to a significant transformation of Cr from mobile fractions to the RES fraction. Therefore, organic ligands played a dominant role in mobility and bioavailability of Cr and the removal of Cr by adsorbents. PMID:27139119

  17. Schistosoma mansoni: possible involvement of protein kinase C in linoleic acid-induced proteolytic enzyme release from cercariae.

    PubMed

    Matsumura, K; Mitsui, Y; Sato, K; Sakamoto, M; Aoki, Y

    1991-04-01

    The possible involvement of protein kinase C and Ca2+ metabolism in the proteolytic enzyme release from schistosome cercariae was studied. Cercariae were placed in dechlorinated tap water containing 0.37 mM calcium in the small glass petri dish and exposed to the stimuli (linoleic acid, phorbol esters, and Ca2+ ionophore) with or without inhibitors of protein kinase C or Ca2+ metabolism. The proteolytic activity of incubation medium of cercariae thus treated was measured by the azocoll assay. The penetration response of cercariae induced by linoleic acid, a physiological stimulus, was mimicked by phorbol esters. When exposed to phorbol esters, 0.02 to 2 microM of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 0.2 to 2 microM of phorbol-12,13-dibutyrate (PDBu), cercariae ceased the swimming movement, began a rhythmic thrusting of the anterior tip of the parasite, and released the proteolytic enzyme, but they did not shed the tails. Lowering Ca2+ in water by addition of 5 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), phorbol ester-induced release of enzyme was completely inhibited. Phorbol ester-induced release of enzyme was partially inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C, at a concentration of 100 microM. H-7 alone, at a concentration of 100 microM, did not affect the swimming movement of cercariae. The cercariae were stimulated to release the enzyme by high concentrations (10 and 100 microM) of the Ca2+ ionophore, A23187, but enzyme was not released by low concentrations (0.5 and 1 microM) of this drug. Cercariae exposed to A23187 behaved differently from those exposed to phorbol esters. They ceased swimming, showed strong muscle contraction, and shed their tail. A23187 stimulated cercariae to release the enzyme in the water containing 5 mM EGTA. A23187-induced enzyme release was not inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin

  18. Aluminum Tolerance Genes on the Short Arm of Chromosome 3R Are Linked to Organic Acid Release in Triticale1

    PubMed Central

    Ma, Jian Feng; Taketa, Shin; Yang, Zhen Ming

    2000-01-01

    Triticale, a hybrid between wheat and rye, shows a high degree of Al tolerance that is inherited from rye, but the mechanisms of high Al tolerance in both rye and triticale are unknown. We found that the short arm of chromosome 3R carries genes necessary for Al tolerance in triticale (× Triticosecale Wittmark cv Currency). Detailed comparative studies with a 3DS.3RL translocation line (ST22) and a non-substitution line (ST2) were conducted. Root elongation was similarly inhibited by Al in ST2 and ST22 during the first 12 h of Al treatment, but more strongly in ST22 than in ST2 at 18 h and thereafter. The root inhibition induced by other metals (Cu, Cd, and La) was similar between ST2 and ST22, suggesting that the action of the genes for Al tolerance on the short arm of triticale chromosome 3R is highly specific to Al. A 2-fold larger amount of malate and citrate was released from the roots of ST2 than from ST22 at 12 and 18 h after Al treatment, respectively. The marked lag phase in the inhibition of root elongation and the release of organic acids implies that the expression of genes on the short arm of triticale chromosome 3R is induced by Al, and that these genes are necessary for the release of organic acids. PMID:10712531

  19. Influence of the backbone structure on the release of bioactive volatiles from maleic acid-based polymer conjugates.

    PubMed

    Berthier, Damien L; Paret, Nicolas; Trachsel, Alain; Herrmann, Andreas

    2010-11-17

    Poly(maleic acid monoester)-based β-mercapto ketones were synthesized and investigated as potential delivery systems for the controlled release of bioactive, volatile, α,β-unsaturated enones (such as damascones and damascenones) by retro 1,4-addition. The bioconjugates were prepared in a one-pot synthesis using 2-mercaptoethanol as a linker. The thiol group of 2-mercaptoethanol adds to the double bond of the enone to form a β-mercapto ketone, which was then grafted via nucleophilic ring-opening of the remaining alcohol function onto a series of alternating copolymers of maleic anhydride and 1-octadecene, ethylene, isobutylene, and methyl vinyl ether. The influence of copolymer backbones on the release of δ-damascone was investigated in buffered aqueous solution as a function of pH and time. In the presence of a cationic surfactant, the polymer conjugates were transferred from an aqueous medium to a cotton surface. The deposition and the release of δ-damascone from the cotton surface as a function of the polymer backbone structure were measured by fluorescence spectroscopy and dynamic headspace analysis, respectively. All polymer conjugates were found to deliver higher amounts of the volatile into the headspace than the reference consisting of unmodified δ-damascone. Polymers with a hydrophobic backbone were generally efficiently deposited on the cotton surface, but released δ-damascone only moderately in solution. Conjugates with a more hydrophilic backbone release the active compound more efficiently in water, but are deposited to a lower extent onto the target surface. A good balance of the hydrophobicity and hydrophilicity of the polymer backbone is the key factor to maximize the deposition of the conjugates on the target surface and to optimize the release of the bioactive volatiles. PMID:20936844

  20. Quantification and evidence for mechanically metered release of pygidial secretions in formic acid-producing carabid beetles.

    PubMed

    Will, Kipling W; Gill, Aman S; Lee, Hyeunjoo; Attygalle, Athula B

    2010-01-01

    This study is the first to measure the quantity of pygidial gland secretions released defensively by carabid beetles (Coleoptera: Carabidae) and to accurately measure the relative quantity of formic acid contained in their pygidial gland reservoirs and spray emissions. Individuals of three typical formic acid producing species were induced to repeatedly spray, ultimately exhausting their chemical compound reserves. Beetles were subjected to faux attacks using forceps and weighed before and after each ejection of chemicals. Platynus brunneomarginatus (Mannerheim) (Platynini), P. ovipennis (Mannerheim) (Platynini) and Calathus ruficollis Dejean (Sphodrini), sprayed average quantities with standard error of 0.313 +/- 0.172 mg, 0.337 +/- 0.230 mg, and 0.197 +/- 0.117 mg per spray event, respectively. The quantity an individual beetle released when induced to spray tended to decrease with each subsequent spray event. The quantity emitted in a single spray was correlated to the quantity held in the reservoirs at the time of spraying for beetles whose reserves are greater than the average amount emitted in a spray event. For beetles with a quantity less than the average amount sprayed in reserve there was no significant correlation. For beetles comparable in terms of size, physiological condition and gland reservoir fullness, the shape of the gland reservoirs and musculature determined that a similar effort at each spray event would mechanically meter out the release so that a greater amount was emitted when more was available in the reservoir. The average percentage of formic acid was established for these species as 34.2%, 73.5% and 34.1% for for P. brunneomarginatus, P. ovipennis and C. ruficollis, respectively. The average quantities of formic acid released by individuals of these species was less than two-thirds the amount shown to be lethal to ants in previously published experiments. However, the total quantity from multiple spray events from a single individual

  1. Quantification and Evidence for Mechanically Metered Release of Pygidial Secretions in Formic Acid-Producing Carabid Beetles

    PubMed Central

    Will, Kipling W.; Gill, Aman S.; Lee, Hyeunjoo; Attygalle, Athula B.

    2010-01-01

    This study is the first to measure the quantity of pygidial gland secretions released defensively by carabid beetles (Coleoptera: Carabidae) and to accurately measure the relative quantity of formic acid contained in their pygidial gland reservoirs and spray emissions. Individuals of three typical formic acid producing species were induced to repeatedly spray, ultimately exhausting their chemical compound reserves. Beetles were subjected to faux attacks using forceps and weighed before and after each ejection of chemicals. Platynus brunneomarginatus (Mannerheim) (Platynini), P. ovipennis (Mannerheim) (Platynini) and Calathus ruficollis Dejean (Sphodrini), sprayed average quantities with standard error of 0.313 ± 0.172 mg, 0.337 ± 0.230 mg, and 0.197 ± 0.117 mg per spray event, respectively. The quantity an individual beetle released when induced to spray tended to decrease with each subsequent spray event. The quantity emitted in a single spray was correlated to the quantity held in the reservoirs at the time of spraying for beetles whose reserves are greater than the average amount emitted in a spray event. For beetles with a quantity less than the average amount sprayed in reserve there was no significant correlation. For beetles comparable in terms of size, physiological condition and gland reservoir fullness, the shape of the gland reservoirs and musculature determined that a similar effort at each spray event would mechanically meter out the release so that a greater amount was emitted when more was available in the reservoir. The average percentage of formic acid was established for these species as 34.2%, 73.5% and 34.1% for for P. brunneomarginatus, P. ovipennis and C. ruficollis, respectively. The average quantities of formic acid released by individuals of these species was less than two-thirds the amount shown to be lethal to ants in previously published experiments. However, the total quantity from multiple spray events from a single individual could

  2. SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

    PubMed

    Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

    2016-01-01

    A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension. PMID:27008813

  3. Induction of inflammatory mediator release (serotonin and 12-hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid.

    PubMed Central

    König, B; Bergmann, U; König, W

    1992-01-01

    Purified glycolipid from Pseudomonas aeruginosa induced the generation of significant amounts of 12-hydroxyeicosatetraenoic acid (12-HETE) and serotonin release from human platelets. The release of serotonin was first observed 2 min after addition of the glycolipid and increased with time. Significant serotonin release was obtained at glycolipid concentrations above 5 micrograms/ml and increased dose-dependently up to 100% at glycolipid concentrations above 40 micrograms/ml. Glycolipid induced 12-HETE in a time- and dose-dependent manner. 12-HETE formation was first measured after 10 min of incubation and increased with time. Optimal 12-HETE formation was obtained at a glycolipid concentration of 50 micrograms/ml; higher concentrations of glycolipid led to a decrease in 12-HETE formation, indicating a cytotoxic effect. Stimulation of platelets with glycolipid (12-HETE formation and serotonin release) was accompanied by calcium influx, translocation of protein kinase C, activation of guanylylimidodiphosphate binding, and increased GTPase activity in platelet membranes within the same concentration range. PMID:1639485

  4. Fatty acyl specificity of the receptor-mediated release of polyunsaturated fatty acids from vascular endothelial cells

    SciTech Connect

    Rosenthal, M.D.

    1987-05-01

    Histamine and bradykinin appear to exhibit the same fatty acid specificity as thrombin. Incubation of human umbilical vein endothelial cells with 10 ..mu..M histamine for 10 min in buffered saline containing 50 ..mu..M fat-free albumin stimulates the release of previously incorporated (/sup 14/C)arachidonate but not (/sup 14/C)22:4(n-6) or (/sup 14/C)20:3(n-6). Similarly calf pulmonary artery endothelial cells release (/sup 14/C)arachidonate but not (/sup 14/C)22:4(n-6) in response to either bradykinin (1 /sup +/g/ml) or histamine (10..mu..M). In both types of endothelial cells, the calcium ionophore A23187 (10 ..mu..M) exhibits the same pattern of fatty acyl specificity as the receptor-mediated agonists. By contrast, mellitin (2-4 ..mu..g/ml) stimulates the release of free 22:4(n-6) and oleate in addition to arachidonate; release of 22:4(n-6) is 30-70% that of arachidonate. These results suggest that histamine, bradykinin and thrombin stimulate a common calcium-dependent fatty acyl-specific phospholipase activity.

  5. Tranexamic acid loaded gellan gum-based polymeric microbeads for controlled release: in vitro and in vivo assessment.

    PubMed

    Bhattacharya, Shiv Sankar; Banerjee, Subham; Chowdhury, Purojit; Ghosh, Amitava; Hegde, Rahul Rama; Mondal, Ranjit

    2013-12-01

    Gellan gum (GG) microbeads containing tranexamic acid (TA), an anti-fibrinolytic drug were prepared by a classic sol-gel transition induced by ionic crosslinking technique using aluminum chloride (AlCl3) as cross-linking agent. The influence of different formulation variables on in vitro physico-chemical parameters and drug release studies were performed systematically. The microbeads were evaluated by scanning electron microscopy (SEM), Fourier transform infra-red (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and high performance liquid chromatographic (HPLC) analysis. Particle size and swelling behavior of microbeads were also investigated. Microbeads showed improved drug encapsulation efficiency along with enhanced drug release. The in vivo studies exhibited sustained drug release in rabbits over a prolonged period after oral administration of these newly developed TA loaded GG microbeads. Based on the results of in vitro and in vivo studies in experimental animal model it was concluded that these microbeads provided intestinal specific controlled release of TA. PMID:24183265

  6. Nitric acid passivation of Ti6Al4V reduces thickness of surface oxide layer and increases trace element release.

    PubMed

    Callen, B W; Lowenberg, B F; Lugowski, S; Sodhi, R N; Davies, J E

    1995-03-01

    Passivation of Ti6Al4V and cpTi implants using methods based on the ASTM-F86 nitric acid protocol are used with the intention of reducing their surface reactivity, and consequently the corrosion potential, in the highly corrosive biologic milieu. The ASTM-F86 passivation protocol was originally developed for surgical implants made of stainless steel and chrome cobalt alloy. Using X-ray photoelectron spectroscopy (XPS) to examine the effect of nitric acid passivation on the surface oxide layer of mill-annealed Ti6Al4V and cpTi, we have found that such treatment actually reduced the oxide thickness on the alloy while having no significant effect on the pure metal. These results correlated with observations obtained using graphite furnace atomic absorption spectrophotometry (GFAAS) to detect trace element release from solid, mill-annealed, Ti6Al4V and cpTi into serum-containing culture medium. We detected significantly greater levels of Ti, Al, and V in the presence of passivated compared to nonpassivated Ti6Al4V. In contrast, nitric acid passivation did not influence Ti release from mill-annealed cpTi. These results, derived from two mill-annealed Ti-based metals, would indicate that re-examination of ASTM-F86-based passivation protocols with respect to Ti6Al4V should be considered in view of the widespread use of this alloy for biomedical devices. PMID:7615579

  7. Chitosan-hyaluronic acid polyelectrolyte complex scaffold crosslinked with genipin for immobilization and controlled release of BMP-2.

    PubMed

    Nath, Subrata Deb; Abueva, Celine; Kim, Boram; Lee, Byong Taek

    2015-01-22

    Polyelectrolyte complex (PEC) is formed when polymers with opposite charges are combined in solution. PECs are recently gaining attention as carriers for controlled release of drugs and proteins. Herein, bone morphogenetic protein-2 (BMP-2) was immobilized in a PEC of natural polymers, chitosan and hyaluronic acid. Charge-to-charge stoichiometry of the formed PEC was estimated based on turbidity of combined chitosan and hyaluronic acid solutions. Free amino groups in chitosan were crosslinked with different amounts of genipin. The degree of crosslinking, consequently its effects in vitro in terms of swelling, degradation and cytocompatibility were analyzed. Immobilization of three different amount of BMP-2 in chitosan-hyaluronic acid PEC scaffold resulted sustained release of the growth factor for more than 30 days. Immobilization efficacies varied from 61% to 76% depending on the amount of BMP-2. Finally effects in osteogenic differentiation of the PEC with BMP-2 to MC3T3-E1 cells were determined by reverse transcriptase PCR. PMID:25439881

  8. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): modifying serotonin's downstream effects on glutamate and GABA (gamma amino butyric acid) release.

    PubMed

    Stahl, Stephen M

    2015-08-01

    Vortioxetine is an antidepressant with multiple pharmacologic modes of action at targets where serotonin neurons connect with other neurons. These actions modify the release of both glutamate and GABA (gamma amino butyric acid) within various brain circuits. PMID:26062900

  9. Studies of manufacturing controlled-release graphene acid and catalyzing synthesis of chalcone with Claisen-Schmidt condensation reaction

    NASA Astrophysics Data System (ADS)

    Li, Jihui; Feng, Jia; Li, Mei; Wang, Qiaolian; Su, Yumin; Jia, Zhixin

    2013-07-01

    In the paper, graphene acid (GA) was manufactured, using flake graphite as raw material, and the acidity and the structure of GA were characterized as well as. Then, chalcone was synthesized in the presence of GA, using acetophenone and benzaldehyde as the reactant. The results showed that the acidity of GA was for pH = 1.12 in aqueous solution, and it was structured by the graphene sheets with the spaces between the graphene sheet and the graphene sheet and sulfuric acid (H2SO4) and acetic acid (CH3CO2H) inside the spaces. At the same time, the results also exhibited that the chalcone yield was able to reach 60.36% when GA dosage was 5 g, and the chalcone yields could attain apart 60.36, 52.05 and 31.16% when 5 g of GA was used thrice. This shows that GA is not only a high-performance catalyst, but also a controlled-release catalyst.

  10. Experimental and chemoinformatics evaluation of some physicochemical properties of excipients influencing release kinetics of the acidic drug ibuprofen.

    PubMed

    Gaikwad, Vinod L; Bhatia, Manish S; Singhvi, Indrajeet

    2015-11-01

    In the present study, ibuprofen, a nonsteroidal anti-inflammatory drug was used in the formulation of tablets using three polymers representing different categories (immediate, moderate and extended release). Prepared tablets were evaluated for different post-compression parameters including dissolution and transportability studies. In vitro dissolution studies indicated Korsmeyer-Peppas as a best fit model, however, the transport of the drug was found to be influenced by its rate of release. A total of 118 molecular descriptors representing physicochemical and topological properties of polymeric structure was calculated and correlated with formulation characteristics for model generation. Further, predictive quantitative-structure property relationship models were developed for correlating polymeric descriptors with formulation properties containing acidic drug (ibuprofen). Developed models exhibited good predictability for formulation characteristics as indicated by squared correlation coefficients (>0.9). Such models could have an ability to predict the formulation properties as well as composition for desired characteristics with saving of time, material and cost. PMID:26197081

  11. Poly(acrylic acid)-block-poly(vinyl alcohol) anchored maghemite nanoparticles designed for multi-stimuli triggered drug release

    NASA Astrophysics Data System (ADS)

    Liu, Ji; Detrembleur, Christophe; Debuigne, Antoine; de Pauw-Gillet, Marie-Claire; Mornet, Stéphane; Vander Elst, Luce; Laurent, Sophie; Labrugère, Christine; Duguet, Etienne; Jérôme, Christine

    2013-11-01

    Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene blue (MB), a cationic model drug. The triggered release of MB was studied under various stimuli such as pH, ionic strength and temperature. Local heating generated under alternating magnetic field (AMF) application was studied, and remotely AMF-triggered release was also confirmed, while a mild heating-up of the release medium was observed. Furthermore, their potential application as magnetic resonance imaging (MRI) contrast agents was explored via relaxivity measurements and acquisition of T2-weighted images. Preliminary studies on the cytotoxicity against mouse fibroblast-like L929 cell line and also their cellular uptake within human melanoma MEL-5 cell line were carried out. In conclusion, this kind of stimuli-responsive nanoparticles appears to be promising carriers for delivering drugs to some tumour sites or into cellular compartments with an acidic environment.Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene

  12. Preparation and controlled-release studies of a protocatechuic acid-magnesium/aluminum-layered double hydroxide nanocomposite

    PubMed Central

    Barahuie, Farahnaz; Hussein, Mohd Zobir; Hussein-Al-Ali, Samer Hasan; Arulselvan, Palanisamy; Fakurazi, Sharida; Zainal, Zulkarnain

    2013-01-01

    In the study reported here, magnesium/aluminum (Mg/Al)-layered double hydroxide (LDH) was intercalated with an anticancer drug, protocatechuic acid, using ion-exchange and direct coprecipitation methods, with the resultant products labeled according to the method used to produce them: “PANE” (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the ion-exchange method) and “PAND” (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the direct method), respectively. Powder X-ray diffraction and Fourier transform infrared spectroscopy confirmed the intercalation of protocatechuic acid into the inter-galleries of Mg/Al-LDH. The protocatechuic acid between the interlayers of PANE and PAND was found to be a monolayer, with an angle from the z-axis of 8° for PANE and 15° for PAND. Thermogravimetric and differential thermogravimetric analysis results revealed that the thermal stability of protocatechuic acid was markedly enhanced upon intercalation. The loading of protocatechuic acid in PANE and PAND was estimated to be about 24.5% and 27.5% (w/w), respectively. The in vitro release study of protocatechuic acid from PANE and PAND in phosphate-buffered saline at pH 7.4, 5.3, and 4.8 revealed that the nanocomposites had a sustained release property. After 72 hours incubation of PANE and PAND with MCF-7 human breast cancer and HeLa human cervical cancer cell lines, it was found that the nanocomposites had suppressed the growth of these cancer cells, with a half maximal inhibitory concentration of 35.6 μg/mL for PANE and 36.0 μg/mL for PAND for MCF-7 cells, and 19.8 μg/mL for PANE and 30.3 μg/mL for PAND for HeLa cells. No half maximal inhibitory concentration for either nanocomposite was found for 3T3 cells. PMID:23737666

  13. Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release.

    PubMed

    Song, Fangfang; Hu, Weikang; Xiao, Longqiang; Cao, Zheng; Li, Xiaoqiong; Zhang, Chao; Liao, Liqiong; Liu, Lijian

    2015-01-01

    Hyaluronic acid (HA) is made up of repeating disaccharide units (β-1,4-d-glucuronic acid and β-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed in situ cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33 h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. In situ three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices. PMID:25598448

  14. Assessment of Heat Resistance of Bacterial Spores from Food Product Isolates by Fluorescence Monitoring of Dipicolinic Acid Release

    PubMed Central

    Kort, Remco; O'Brien, Andrea C.; van Stokkum, Ivo H. M.; Oomes, Suus J. C. M.; Crielaard, Wim; Hellingwerf, Klaas J.; Brul, Stanley

    2005-01-01

    This study is aimed at the development and application of a convenient and rapid optical assay to monitor the wet-heat resistance of bacterial endospores occurring in food samples. We tested the feasibility of measuring the release of the abundant spore component dipicolinic acid (DPA) as a probe for heat inactivation. Spores were isolated from the laboratory type strain Bacillus subtilis 168 and from two food product isolates, Bacillus subtilis A163 and Bacillus sporothermodurans IC4. Spores from the lab strain appeared much less heat resistant than those from the two food product isolates. The decimal reduction times (D values) for spores from strains 168, A163, and IC4 recovered on Trypticase soy agar were 1.4, 0.7, and 0.3 min at 105°C, 120°C, and 131°C, respectively. The estimated Z values were 6.3°C, 6.1°C, and 9.7°C, respectively. The extent of DPA release from the three spore crops was monitored as a function of incubation time and temperature. DPA concentrations were determined by measuring the emission at 545 nm of the fluorescent terbium-DPA complex in a microtiter plate fluorometer. We defined spore heat resistance as the critical DPA release temperature (Tc), the temperature at which half the DPA content has been released within a fixed incubation time. We found Tc values for spores from Bacillus strains 168, A163, and IC4 of 108°C, 121°C, and 131°C, respectively. On the basis of these observations, we developed a quantitative model that describes the time and temperature dependence of the experimentally determined extent of DPA release and spore inactivation. The model predicts a DPA release rate profile for each inactivated spore. In addition, it uncovers remarkable differences in the values for the temperature dependence parameters for the rate of spore inactivation, DPA release duration, and DPA release delay. PMID:16000762

  15. Effect Of Imposed Anaerobic Conditions On Metals Release From Acid-Mine Drainage Contaminated Streambed Sediments

    EPA Science Inventory

    Remediation of streams influenced by mine-drainage may require removal and burial of metal-containing bed sediments. Burial of aerobic sediments into an anaerobic environment may release metals, such as through reductive dissolution of metal oxyhydroxides. Mining-impacted aerob...

  16. Controlled release of linalool using nanofibrous membranes of poly(lactic acid) obtained by electrospinning and solution blow spinning: A comparative study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofib...

  17. Effect of imposed anaerobic conditions on metals release from acid-mine drainage contaminated streambed sediments.

    PubMed

    Butler, Barbara A

    2011-01-01

    Remediation of streams influenced by mine-drainage may require removal and burial of metal-containing bed sediments. Burial of aerobic sediments into an anaerobic environment may release metals, such as through reductive dissolution of metal oxyhydroxides. Mining-impacted aerobic streambed sediments collected from North Fork Clear Creek, Colorado were held under anaerobic conditions for four months. Eh, pH, and concentrations of Cd, Cu, Fe, Mn, and Zn (filtered at 1.5 μm, 0.45 μm, and 0.2 μm), sulfate, and dissolved organic carbon (DOC) were monitored in stream water/sediment slurries. Two sediment size fractions were examined (2 mm-63 μm and <63 μm). Sequential extractions evaluated the mineral phase with which metals were associated in the aerobic sediment. Released Cu was re-sequestered within 5 weeks, while Fe and Mn still were present at 16 weeks. Mn concentration was lower than in the initial stream water at and beyond 14 weeks for the smaller sized sediment. Cd was not released from either sediment size fraction. Zn was released at early times, but concentrations never exceeded those present in the initial stream water and all was re-sequestered over time. The greatest concentrations of Cu, Fe, Mn, and Zn were associated with the Fe/Mn reducible fraction. Sulfate and Fe were strongly correlated (r = 0.90), seeming to indicate anaerobic dissolution of iron oxy-hydroxy-sulfate minerals. DOC and sulfate were strongly correlated (r = 0.81), with iron having a moderately strong correlation with DOC (r = 0.71). Overall concentrations of DOC, sulfate, Cu, Fe, and Zn and pH were significantly higher (p < 0.05) in the water overlying the small sized sediment samples, while the concentrations of Mn released from the larger sized sediment samples were greater. PMID:20709348

  18. Reproductive Biology of Selaginella: I. Determination of Megasporangia by 2-Chloroethylphosphonic Acid, an Ethylene-releasing Compound.

    PubMed

    Brooks, K E

    1973-04-01

    Control clumps of Selaginella wallacei Heiron., sprayed with distilled water with Tween 20, produced a high proportion of microsporangia. Similar clumps sprayed with 2-chlorethyl-phosphonic acid, and ethylene-releasing compound (Ethephon), at 7.65 and 76.5 mg/liter produced almost exclusively megasporangia. Treatment of Selaginella pallescens (Presl) Spring with Ethephon at 34 mg/liter caused the production of megasporangia in the microsporangiate files of the strobili. The possibility that ethylene may be involved in the regulation of heterospory in Selaginella is discussed. PMID:16658398

  19. Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2.

    PubMed

    Xu, Xian; Jha, Amit K; Duncan, Randall L; Jia, Xinqiao

    2011-08-01

    We are interested in developing hydrophilic particulate systems that are capable of sequestering growth factors, regulating their release and potentiating their biological functions. To this end heparin (HP)-decorated, hyaluronic acid (HA)-based hydrogel particles (HGPs) were synthesized using an inverse emulsion polymerization technique employing divinyl sulfone as the crosslinker. By varying the feed composition of the aqueous phase the amount of HP integrated in the particles can be systematically tuned. The resulting microscopic particles are spherical in shape and contain nanosized pores suitable for growth factor encapsulation. The covalently immobilized HP retained its ability to bind bone morphogenetic protein-2 (BMP-2) specifically, and its release kinetics can be adjusted by tuning the particle composition. Compared with pure HA particles the hybrid HA/HP HGPs show a higher BMP-2 loading capacity. While BMP-2 was released from HA HGPs with a significant initial burst, a near zero order release kinetics was observed from HA/HP hybrid particles with an optimized heparin content of 0.55 μg per mg HGPs. The ability of HA/HP hybrid particles to present BMP-2 in a controlled manner, combined with the innate bioactivity of HA, induced robust and consistent chondrogenic differentiation of murine mesenchymal stem cells, as shown by up-regulation of the mRNA levels of chondrogenic markers and the production of cartilage-specific extracellular matrix components. The simplicity of the particle synthesis, combined with the defined biological activities of the constituent building blocks, renders the HP-decorated, HA-based hydrogel particle system an attractive candidate for the sustained release of BMP-2, possibly for cartilage repair and regeneration. PMID:21550426

  20. Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane

    SciTech Connect

    Ray, R.; Legere, R.H.; Majerus, B.J.; Petrali, J.P.

    1995-12-31

    The mechanism of action of the alkylating agent bis-(2-chloroethyl)sulfide (sulfur mustard, SM) was studied using the in thai vitro mouse neuroblastoma-rat glioma hybrid NG 108-1 S clonal p cell line model. Following 0.3 mM SM exposure, cell viability remained high (>80% of untreated control) up to 9 hr and then declined steadily to about 40% of control after 20-24 hr. During the early period of SM exposure, when there was no significant cell viability loss, the following effects were observed. The cellular glutathione level decreased 20% after 1 hr and 34% after 6 hr. Between 2 and 6 hr, there was a time-dependent increase (about 10 to 30%) in intracellular free calcium (Ca2+), which was localized to the limiting membrane of swollen endoplasmic reticula and mitochondria, to euchromatin areas of the nucleus, and to areas of the cytosol and plasma membrane. Moreover,there was also a time-dependent increase in the release of isotopically labeled arachidonic acid ((3H)AA) from cellular membranes. Increase in (3H)AA release was 28% at 3 hr and about 60-80% between 6 and 9 hr. This increase in I3HIAA release was inhibited by quinacrine (20 uM), which is a phospholipase (PLA2) inhibitor. At 16 hr after SM exposure, there was a large increase (about 200% of control) in I3HIAA release, which was coincident with a 50% loss of cell viability. These results suggest a Ca2+-mediated toxic mechanism of SM via PLA2 activation and arachidonate release.

  1. Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2

    PubMed Central

    Xu, Xian; Jha, Amit K.; Duncan, Randall L.; Jia, Xinqiao

    2011-01-01

    We are interested in developing hydrophilic particulate systems that are capable of sequestering growth factors, regulating their release and potentiating their biological functions. Towards this end, heparin (HP)-decorated, hyaluronic acid (HA)-based, hydrogel particles (HGPs) were synthesized using an inverse emulsion polymerization technique employing divinyl sulfone as the crosslinker. By varying the feed composition of the aqueous phase, the amount of heparin integrated in the particles can be systematically tuned. The resulting microscopic particles are spherical in shape and contain nanosized pores suitable for growth factor encapsulation. The covalently immobilized heparin retained its ability to bind bone morphogenetic protein 2 (BMP-2) specifically, and its release kinetics can be adjusted by tuning the particle composition. Compared to the pure HA particles, the hybrid HA/HP HGPs show a higher BMP-2 loading capacity. While BMP-2 was released from HA HGPs with a significant initial burst, a near zero-order release kinetics was observed from HA/HP hybrid particles with an optimized heparin content of 0.55 μg per milligram HGPs. The ability of HA/HP hybrid particles to present BMP-2 in a controlled manner, combined with the innate bioactivity of HA, induced robust and consistent chondrogenic differentiation of murine mesenchymal stem cells, as evidenced by the up-regulation of mRNA levels of chondrogenic markers and the production of cartilage-specific extracellular matrix components. The simplicity of the particle synthesis, combined with the defined biological activities of the constituent building blocks, renders the HP-decorated, HA-based hydrogel particle system an attractive candidate for the sustained release of BMP-2, possibly for cartilage repair and regeneration. PMID:21550426

  2. Oxidation of formic acid by oxyanions of chlorine and its implications to the Viking Labeled Release experiment

    NASA Astrophysics Data System (ADS)

    Martinez, P.; Navarro-gonzalez, R.

    2013-05-01

    The Viking Landers that arrived on Mars in 1976 carried out three biological experiments designed to investigate if there was microbial life. These were the Gas-Exchange, Pyrolitic Release and Labeled Release experiments. The three experiments yielded positive responses but the Labeled Release experiment had a kinetic response indicative of microbial activity. The experiment consisted of adding a broth of nutrients (formic acid, glycolic acid, glycine, D- and L-alanine and D- and L-lactic acid uniformly marked with 14C) to martian soil samples. The results were surprising; the nutrients were consumed releasing radioactive gases in a manner that is compatible by terrestrial microorganisms. The existence of Martian life was contradicted by soil chemical analysis that indicated the absence of organic compounds above the detection limits of parts per billion (ppb). Instead the positive response of the Labeled Release Experiment was attributed to the existence of peroxides and/or superoxides in the Martian soils that destroyed the nutrients upon contact. Recently, the Phoenix mission that landed in the Martian Arctic in 2008 revealed the presence of a highly oxidized form of the element chlorine in the soil: perchlorate. Perchlorate is thought to have formed in the Martian atmosphere by the oxidation of chloride from volcanic sources with ozone. Therefore perchlorate is formed by the stepwise oxidation of hypochlorite, chlorite and chlorate. These oxyanions of chlorine are powerful oxidizers that may exist in the Martian soil and may have reacted with the nutrients of the Labeled Release Experiment. This paper aims to better understand these results by designing experiments to determine the kinetics of decomposition of formic acid to carbon dioxide with different oxidized forms of chlorine by headspace technique in gas chromatography coupled to mass spectrometry (GC / MS). Previous studies done in the laboratory showed that only hypochlorite quantitatively reacted with

  3. PAR-2 activation enhances weak acid-induced ATP release through TRPV1 and ASIC sensitization in human esophageal epithelial cells.

    PubMed

    Wu, Liping; Oshima, Tadayuki; Shan, Jing; Sei, Hiroo; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2015-10-15

    Esophageal visceral hypersensitivity has been proposed to be the pathogenesis of heartburn sensation in nonerosive reflux disease. Protease-activated receptor-2 (PAR-2) is expressed in human esophageal epithelial cells and is believed to play a role in inflammation and sensation. PAR-2 activation may modulate these responses through adenosine triphosphate (ATP) release, which is involved in transduction of sensation and pain. The transient receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels (ASICs) are both acid-sensitive nociceptors. However, the interaction among these molecules and the mechanisms of heartburn sensation are still not clear. We therefore examined whether ATP release in human esophageal epithelial cells in response to acid is modulated by TRPV1 and ASICs and whether PAR-2 activation influences the sensitivity of TRPV1 and ASICs. Weak acid (pH 5) stimulated the release of ATP from primary human esophageal epithelial cells (HEECs). This effect was significantly reduced after pretreatment with 5-iodoresiniferatoxin (IRTX), a TRPV1-specific antagonist, or with amiloride, a nonselective ASIC blocker. TRPV1 and ASIC3 small interfering RNA (siRNA) transfection also decreased weak acid-induced ATP release. Pretreatment of HEECs with trypsin, tryptase, or a PAR-2 agonist enhanced weak acid-induced ATP release. Trypsin treatment led to the phosphorylation of TRPV1. Acid-induced ATP release enhancement by trypsin was partially blocked by IRTX, amiloride, or a PAR-2 antagonist. Conversely, acid-induced ATP release was augmented by PAR-2 activation through TRPV1 and ASICs. These findings suggested that the pathophysiology of heartburn sensation or esophageal hypersensitivity may be associated with the activation of PAR-2, TRPV1, and ASICs. PMID:26294672

  4. Formic acid as a hydrogen storage material - development of homogeneous catalysts for selective hydrogen release.

    PubMed

    Mellmann, Dörthe; Sponholz, Peter; Junge, Henrik; Beller, Matthias

    2016-07-11

    Formic acid (FA, HCO2H) receives considerable attention as a hydrogen storage material. In this respect, hydrogenation of CO2 to FA and dehydrogenation of FA are crucial reaction steps. In the past decade, for both reactions, several molecularly defined and nanostructured catalysts have been developed and intensively studied. From 2010 onwards, this review covers recent advancements in this area using homogeneous catalysts. In addition to the development of catalysts for H2 generation, reversible H2 storage including continuous H2 production from formic acid is highlighted. Special focus is put on recent progress in non-noble metal catalysts. PMID:27119123

  5. Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells.

    PubMed

    Irvine, Nicola A; Lillycrop, Karen A; Fielding, Barbara; Torrens, Christopher; Hanson, Mark A; Burdge, Graham C

    2015-10-01

    Stimulation of vascular smooth muscle (VSM) α1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. Δ6 (D6d) and Δ5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2α secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction. PMID:26324193

  6. Fabrication of a bioadhesive transdermal device from chitosan and hyaluronic acid for the controlled release of lidocaine.

    PubMed

    Anirudhan, T S; Nair, Syam S; Nair, Anoop S

    2016-11-01

    A novel efficient transdermal (TD) lidocaine (LD) delivery device based on chitosan (CS) and hyaluronic acid (HA) was successfully developed in the present investigation. CS was grafted with glycidyl methacrylate (GMA) and butyl methacrylate (BMA) to fabricate a versatile material with improved adhesion and mechanical properties. HA was hydrophobically modified by covalently conjugating 3-(dimethylamino)-1-propylamine (DMPA) to encapsulate poorly water soluble LD and was uniformly dispersed in modified CS matrix. The prepared materials were characterized through FTIR, NMR, XRD, SEM, TEM and tensile assay. The dispersion of amine functionalized HA (AHA) on modified CS matrix offered strong matrix - filler interaction, which improved the mechanical properties and drug retention behavior of the device. In vitro skin permeation study of LD was performed with modified Franz diffusion cell using rat skin and exhibited controlled release. The influence of storage time on release profile was investigated and demonstrated that after the initial burst, LD release profile of the device after 30 and 60days storage was identical to that of a device which was not stored. In vivo skin adhesion test and skin irritation assay in human subjects, water vapor permeability and environmental fitness test was performed to judge its application in biomedical field. All results displayed that the fabricated device is a potential candidate for TD LD administration to the systemic circulation. PMID:27516320

  7. Mineralization and drug release of hydroxyapatite/poly(l-lactic acid) nanocomposite scaffolds prepared by Pickering emulsion templating.

    PubMed

    Hu, Yang; Zou, Shengwen; Chen, Weike; Tong, Zhen; Wang, Chaoyang

    2014-10-01

    Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled microstructures and able to deliver special drugs have gained increasing attention in bone tissue engineering. In this study, the hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using solvent evaporation from templating Pickering emulsions stabilized with PLLA-modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti-inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The results showed that the NC scaffolds possessed interconnected pore structures, which could be modulated by varying the g-HAp nanoparticle concentration. The NC scaffolds exhibited excellent bioactivity, since they induced the formation of calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a sustained release profile, and the release kinetic followed the Higuchi model with diffusion process. Thus, solvent evaporation based on Pickering emulsion droplets is a simple and effective method to prepare biodegradable and bioactive porous NC scaffolds for bone repair and replacement applications. PMID:25127362

  8. A [NiFe]hydrogenase model that catalyses the release of hydrogen from formic acid.

    PubMed

    Nguyen, Nga T; Mori, Yuki; Matsumoto, Takahiro; Yatabe, Takeshi; Kabe, Ryota; Nakai, Hidetaka; Yoon, Ki-Seok; Ogo, Seiji

    2014-11-11

    We report the decomposition of formic acid to hydrogen and carbon dioxide, catalysed by a NiRu complex originally developed as a [NiFe]hydrogenase model. This is the first example of H2 evolution, catalysed by a [NiFe]hydrogenase model, which does not require additional energy. PMID:25234420

  9. Preliminary Results: Release Of Metals From Acid-Mine Drainage Contaminated Streambed Sediments Under Anaerobic Conditions

    EPA Science Inventory

    Many miles of streams in the western U.S. are contaminated with acid-mine drainage (AMD) from abandoned metal mines. Treatment of these streams may include removal of the existing sediments, with subsequent burial (e.g., in a repository). Burial of previously aerobic sediments ma...

  10. Engineering Saccharomyces cerevisiae to produce feruloyl esterase for the release of ferulic acid from switchgrass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Aspergillus niger ferulic acid esterase gene (faeA) was cloned into Saccharomyces cerevisiae via a yeast expression vector, resulting in efficient expression and secretion of the enzyme in the medium. The recombinant enzyme was purified to homogeneity by anion-exchange and hydrophobic interactio...

  11. Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems

    PubMed Central

    Obermeier, Andreas; Schneider, Jochen; Wehner, Steffen; Matl, Florian Dominik; Schieker, Matthias; von Eisenhart-Rothe, Rüdiger; Stemberger, Axel; Burgkart, Rainer

    2014-01-01

    Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures. PMID:24983633

  12. Improvement of moistness and texture of high omega-3 fatty acid mackerel nuggets by inclusion of moisture-releasing ingredients.

    PubMed

    Lee, K H; Joaquin, H; Lee, C M

    2007-03-01

    In developing mince-based nugget products using mackerel, an abundant, underutilized, high omega-3 fatty acid species, attention was given to moistness and texture improvement with moisture-releasing ingredients. Three basic approaches were used: added water level variation (0 to 35%), varying added water-moisture-releasing vegetable combination (28/0, 21/7, 14/14, 7/21, 0/28), and varying milk-water combination (0/21, 7/14, 14/7, 21/0). Main ingredients of nugget included mackerel mince, mild cheddar cheese, and hydrated textured soy protein concentrate. The formulated products were molded, lightly battered, flash fried, and frozen until tested. Frozen nuggets were cooked to 65 degrees C and subjected to the Instron texture analysis (compressive force CF at 70% deformation, expressible fluid EF) and sensory analysis (firmness F, moistness M, overall desirability OD). The 28% added water, 7% moisture-releasing vegetable at 21% water, and 14:7 and 21:0 milk-water combinations were preferred (P < 0.05). Among the vegetables, onion and mushroom were preferred. Positive correlations were M-OD (r= 0.82), EF-OD (r= 0.54), and EF-M (r= 0.49), and negative correlations were F-OD (r=-0.83) and CF-OD (r=-0.34). Milk was more effective than water in rendering moistness and tender texture. The vegetable was effective in forming and making the cooked product moist with less liquid added by holding moisture release during forming and liquid cells after cooking. During warming under the lamps, the least decreases in sensory score, compressive force, and expressible fluid were observed in nuggets made with vegetable and milk. PMID:17995852

  13. A New Pro-Prodrug Aminoacid-Based for Trans-Ferulic Acid and Silybin Intestinal Release

    PubMed Central

    Trombino, Sonia; Ferrarelli, Teresa; Cassano, Roberta

    2014-01-01

    The aim of this work was the preparation and characterization of a pro-prodrug able to simultaneously transport silybin, a drug possessing various pharmacological effects, and trans-ferulic acid, a known antioxidant. More specifically, l-phenylalanine-N-(4-hydroxy-3-methoxy-phenyl) prop-2-en-O-(2R,3R)-3,5,7-trihydroxy-2-((2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-benzo-(1,4)-dioxin-6-yl)croman-4-one was synthesized by using the aminoacid l-phenylalanine (l-Phe) as carrier. Indeed, l-Phe is characterized by an intrinsic chemical reactivity due to the presence of an amino group, placed on the chiral center, and of a carboxylic group. The synthesis has been characterized first by adding silybin by means of carboxylic group and then, with the aim to confer antioxidant properties to this new carrier, by linking trans-ferulic acid to l-Phe via amino group. The so obtained derivative was then characterized by FT-IR, and 1H-NMR spectroscopies. Furthermore, its ability to inhibit lipid peroxidation induced by tert-butyl hydroperoxide in rat liver microsomes, was evaluated. The 1,1-diphenyl-2-picrylhydrazyl radical-scavenging effect, was also assessed. The release of silybin and trans-ferulic acid was determined in simulated gastric and intestinal fluids over the time. The results showed that the covalent bond between both (i) silybin; or (ii) trans-ferulic acid and the amino acid was degraded by enzymatic reactions. In addition, the pro-prodrug, showed strong antioxidant and scavenger activities. Due to these properties, this new pro-prodrug could be applied for the treatment of intestinal pathologies and it might improve the therapeutic potential of silybin which is strongly limited by its low solubility. PMID:25062426

  14. Release mechanism of omega-3 fatty acid in κ-carrageenan/polydextrose undergoing glass transition.

    PubMed

    Paramita, Vilia Darma; Bannikova, Anna; Kasapis, Stefan

    2015-08-01

    A high-solid matrix of κ-carrageenan with polydextrose was developed to entrap α-linolenic acid, which is an omega-3 bioactive compound. Physicochemical analysis of this system utilised modulated DSC, dynamic oscillation in shear, ESEM, FTIR and WAX diffraction. The carbohydrate matrix was conditioned through an extensive temperature range to induce changes in molecular morphology and identify the network glass transition temperature. Thermally induced variation in phase morphology was employed to rationalise transportation patterns of the bioactive compound within the high-solid preparation. Thus, experimental observations using UV-vis spectroscopy modelled diffusion kinetics to document the mobility arresting effect of the vitrifying matrix on the micro-constituent. Within the glass transition region, results argue that free volume theory is the molecular process governing structural relaxation. Further, Less Fickian diffusion follows well the rate of molecular transport of α-linolenic acid as a function of time and temperature of observation in the condensed matrix. PMID:25933532

  15. Nitric oxide release from nitro-fatty acids in Arabidopsis roots.

    PubMed

    Mata-Pérez, Capilla; Sánchez-Calvo, Beatriz; Begara-Morales, Juan C; Padilla, María N; Valderrama, Raquel; Corpas, Francisco J; Barroso, Juan B

    2016-01-01

    In recent years, research on the involvement of nitric oxide (NO) in plant systems has remarkably grown. However, most of the interest in this molecule has been focused on its ability to mediate different post-translational modifications (NO-PTM) in biomolecules, mainly nitration and S-nitrosylation of proteins, and its involvement in physiological and stress situations. Nevertheless, very recently the nitration of other molecules such as fatty acids has commanded increasingly greater attention. In the last February issue of Plant Physiology, we again reported on the endogenous occurrence of nitro-fatty acids (NO2-FAs), specifically nitro-linolenic acid (NO2-Ln), in the model plant Arabidopsis thaliana. The analysis of the presence of this nitro-fatty acid showed that levels of NO2-Ln decreased throughout the plant development with the higher levels detected in seeds and young seedlings of this plant. Furthermore, through a transcriptomic analysis by RNA-seq technology applying NO2-Ln to A. thaliana cell-suspension cultures, we found high induction in the transcriptional expression of several heat-shock proteins (HSPs) and the enzymes ascorbate peroxidase (APX) and methionine sulfoxide reductase (MSR). Based on these findings, the involvement of NO2-Ln in the NO metabolism was analyzed showing a significant NO formation in roots from 7-day-old Arabidopsis thaliana seedlings and standing out that NO generated from NO2-Ln could have an important role at the beginning of plant development. Therefore, these findings highlight the importance of these novel NO-derived molecules in plant systems playing a pivotal role in development and in the antioxidant defense response against different abiotic stress conditions. PMID:26910757

  16. Free fatty acids released from phospholipids are the major heat-stable hemolytic factor of Entamoeba histolytica trophozoites.

    PubMed Central

    Said-Fernández, S; López-Revilla, R

    1988-01-01

    The major hemolytic activity of Entamoeba histolytica trophozoites is located in a vesicular fraction called P30 and known to be due to heat-labile and heat-stable hemolytic components whose effect increases up to 100 times during preincubation at 36 degrees C. The heat-stable hemolytic activity (HSHA) was found in the chloroform-methanol extract of preincubated P30, whose partition with 2 M KCl yielded a lipid fraction, an interphase, and an aqueous phase. HSHA was detected only in the lipid fraction, where it amounted to 59% of the chloroform-methanol extract activity and increased 50% when supplemented with the interphase material; it was accounted for by the free fatty acids, whose potency increased 33% with the interphase material, and was blocked by delipidated bovine serum albumin. A parallel increase in free fatty acids and lysophospholipids and a corresponding decrease in phospholipids were observed during P30 preincubation. Most of the phospholipase activity of trophozoite homogenates was also found in P30. Therefore, most of the HSHA generated during preincubation was due to free fatty acids released from phospholipids by a P30 phospholipase that may contribute significantly to E. histolytica cytopathogenicity and virulence. Images PMID:2894362

  17. Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production.

    PubMed

    Ronco, A M; Moraga, P F; Llanos, M N

    2002-01-01

    We have previously demonstrated that the release of arachidonic acid (AA) from human chorionic gonadotropin (hCG)-stimulated Leydig cells occurs in a dose- and time-dependent manner. In addition, the amount of AA released was dependent on the hormone-receptor interaction and the concentration of LH-hCG binding sites on the cell surface. The present study was conducted to evaluate the involvement of phospholipase A(2) (PLA(2)) and G proteins in AA release from hormonally stimulated rat Leydig cells, and the possible role of this fatty acid in cAMP production. Cells were first prelabelled with [(14)C]AA to incorporate the fatty acid into cell phospholipids, and then treated in different ways to evaluate AA release. hCG (25 mIU) increased the release of AA to 180+/-12% when compared with AA released from control cells, arbitrarily set as 100%. Mepacrine and parabromophenacyl bromide (pBpB), two PLA(2) inhibitors, decreased the hormone-stimulated AA release to 85+/-9 and 70+/-24% respectively. Conversely, melittin, a PLA(2) stimulator, increased the release of AA up to 200% over control. The inhibitory effect of mepacrine on the release of AA was evident in hCG-treated Leydig cells, but not in the melittin-treated cells. To determine if the release of AA was also mediated through a G protein, cells were first permeabilized and subsequently treated with pertussis toxin or GTPgammaS, a non-hydrolyzable analog of GTP. Results demonstrate that GTPgammaS was able to induce a similar level of the release of AA as hCG. In addition, pertussis toxin completely abolished the stimulatory effect of hCG on the release of AA, indicating that a member of the G(i) family was involved in the hCG-dependent release of AA. Cells treated with PLA(2) inhibitors did not modify cAMP production, but exogenously added AA significantly reduced cAMP production from hCG-treated Leydig cells, in a manner dependent on the concentration of AA and hCG. Results presented here suggest an involvement of

  18. Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake.

    PubMed

    Zheng, Shaohui; Jin, Zhen; Han, Jiwon; Cho, Sunghoon; Nguyen, Van Du; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2016-07-01

    In this study, a novel type of high intensity focused ultrasound (HIFU)-triggered active tumor-targeting polymeric micelle was prepared and investigated for controlled drug release and enhanced cellular uptake. Amphiphilic hyaluronic acid (HA) conjugates were synthesized to form docetaxel loaded micelles in aqueous conditions with high encapsulation efficiencies of over 80%. The micelle sizes were limited to less than 150nm, and they varied slightly according to the encapsulated drug amount. Modifying the micellar surface modification with polyethylene glycol diamine successfully inhibited premature drug leakage at a certain level, and it can be expected to prolong the circulation time of the particles in blood. In addition, high-intensity focused ultrasound was introduced to control the release of docetaxel from micelles, to which the release behavior of a drug can be tuned. The in-vitro cell cytotoxicity of docetaxel-loaded micelles was verified against CT-26 and MDA-MB-231 cells. The IC50 values of drug-loaded micelles to CT-26 and MDA-MB-231 cells were 1230.2 and 870.9ng/mL, respectively. However, when exposed to HIFU, the values decreased significantly, to 181.9 and 114.3ng/mL, suggesting that HIFU can enhance cell cytotoxicity by triggering the release of a drug from the micelles. Furthermore, cellular uptake tests were conducted via the quantitative analysis of intracellular drug concentration within CT-26 (CD44 negative), MDA-MB-231 (CD44 positive), and MDA-MB-231 (CD44 blocked), and then imaged with coumarin-6 loaded micelles. The results verified that intracellular drug delivery can be enhanced efficiently via the CD44 receptor-mediated endocytosis of HA micelles. Moreover, HIFU enhanced the cellular uptake behavior by altering the permeability of the cell membrane. It was also able to aid with the extravasation of micelles into the interior of tumors, which will be explained in further research. Therefore, the present study demonstrates that the micelles

  19. Two Distinct Modes of Hypoosmotic Medium-Induced Release of Excitatory Amino Acids and Taurine in the Rat Brain In Vivo

    PubMed Central

    Haskew-Layton, Renée E.; Rudkouskaya, Alena; Jin, Yiqiang; Feustel, Paul J.; Kimelberg, Harold K.; Mongin, Alexander A.

    2008-01-01

    A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo. PMID:18958155

  20. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: the roles of Galphaq, PLC-beta, IP3 and 5,6-epoxyeicosatrienoic acid.

    PubMed

    Muldowney, James A S; Painter, Corrie A; Sanders-Bush, Elaine; Brown, Nancy J; Vaughan, Douglas E

    2007-02-01

    The acute physiologic release of tissue-type plasminogen activator (t-PA) from the endothelium is critical for vascular homeostasis. This process is prostacyclin- and nitric oxide (NO)-independent in humans. It has been suggested that calcium signaling and endothelial-derived hyperpolarizing factors (EDHF) may play a role in t-PA release. G-protein-coupled receptor-dependent calcium signaling is typically Galphaq-dependent. EDHFs have been functionally defined and in various tissues are believed to be various regioisomers of the epoxyeicosatrienoic acids (EETs). We tested the hypothesis in vitro that thrombin-stimulated t-PA release from human microvascular endothelial cells (HMECs) is both Galphaq- and EDHF-dependent. Conditioned media was harvested following thrombin stimulation, and t-PA antigen was measured by ELISA. Thrombin-induced t-PA release was limited by a membrane-permeable Galphaq inhibitory peptide, the PLC-beta antagonist U73122, and the IP3 receptor antagonist 2-aminoethoxyphenylborane, while the Galphaq agonist Pasteurella toxin modestly induced t-PA release. The cytochrome P450 (CYP450) inhibitor, miconazole, and the arachidonic acid epoxygenase inhibitor MS-PPOH inhibited thrombin-stimulated t-PA release, while 5,6-EET-methyl ester stimulated t-PA release. The 5,6- and 14,15-EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid, inhibited t-PA release at the 100 microM concentration. However, thrombin-stimulated t-PA release was unaffected by the prostacyclin and NO inhibitors ASA and L-NAME, as well as the potassium channel inhibitors TEA, apamin and charybdotoxin. These studies suggest that thrombin-stimulated t-PA release is Galphaq-, PLC-beta-, IP3-, and 5,6-EET-dependent while being prostacyclin-, NO- and K+ channel-independent in HMECs. PMID:17264956

  1. Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility.

    PubMed

    Murase, Remi; Sato, Hiroyasu; Yamamoto, Kei; Ushida, Ayako; Nishito, Yasumasa; Ikeda, Kazutaka; Kobayashi, Tetsuyuki; Yamamoto, Toshinori; Taketomi, Yoshitaka; Murakami, Makoto

    2016-03-25

    Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization. PMID:26828067

  2. Alpha- and beta-Proteobacteria control the consumption and release of amino acids on lake snow aggregates.

    PubMed

    Schweitzer, B; Huber, I; Amann, R; Ludwig, W; Simon, M

    2001-02-01

    aggregate-associated bacteria from the surrounding water. This stage was followed by a period of 1 to 3 days during which dissolved amino acids were released into the surrounding water, paralleled by an increasing dominance of beta-Proteobacteria. Hence, our results show that lake snow aggregates are inhabited by a community dominated by a limited number of alpha- and beta-Proteobacteria, which undergo a distinct succession. They successively decompose the amino acids bound in the aggregates and release substantial amounts into the surrounding water during aging and sinking. PMID:11157226

  3. Abscisic acid (ABA) regulates grape bud dormancy, and dormancy release stimuli may act through modification of ABA metabolism

    PubMed Central

    Zheng, Chuanlin; Halaly, Tamar; Acheampong, Atiako Kwame; Takebayashi, Yumiko; Jikumaru, Yusuke; Kamiya, Yuji; Or, Etti

    2015-01-01

    In warm-winter regions, induction of dormancy release by hydrogen cyanamide (HC) is mandatory for commercial table grape production. Induction of respiratory stress by HC leads to dormancy release via an uncharacterized biochemical cascade that could reveal the mechanism underlying this phenomenon. Previous studies proposed a central role for abscisic acid (ABA) in the repression of bud meristem activity, and suggested its removal as a critical step in the HC-induced cascade. In the current study, support for these assumptions was sought. The data show that ABA indeed inhibits dormancy release in grape (Vitis vinifera) buds and attenuates the advancing effect of HC. However, HC-dependent recovery was detected, and was affected by dormancy status. HC reduced VvXERICO and VvNCED transcript levels and induced levels of VvABA8’OH homologues. Regulation of these central players in ABA metabolism correlated with decreased ABA and increased ABA catabolite levels in HC-treated buds. Interestingly, an inhibitor of ethylene signalling attenuated these effects of HC on ABA metabolism. HC also modulated the expression of ABA signalling regulators, in a manner that supports a decreased ABA level and response. Taken together, the data support HC-induced removal of ABA-mediated repression via regulation of ABA metabolism and signalling. Expression profiling during the natural dormancy cycle revealed that at maximal dormancy, the HC-regulated VvNCED1 transcript level starts to drop. In parallel, levels of VvA8H-CYP707A4 transcript and ABA catabolites increase sharply. This may provide initial support for the involvement of ABA metabolism also in the execution of natural dormancy. PMID:25560179

  4. Poly(ε-caprolactone)/triclosan loaded polylactic acid nanoparticles composite: A long-term antibacterial bionanocomposite with sustained release.

    PubMed

    Kaffashi, Babak; Davoodi, Saeed; Oliaei, Erfan

    2016-07-11

    In this study, the antibacterial bionanocomposites of poly(ε-caprolactone) (PCL) with different concentrations of triclosan (TC) loaded polylactic acid (PLA) nanoparticles (30wt% triclosan) (LATC30) were fabricated via a melt mixing process in order to lower the burst release of PCL and to extend the antibacterial activity during its performance. Due to the PLA's higher glass transition temperature (Tg) and less flexibility compared with PCL; the PLA nanoparticles efficiently trapped the TC particles, reduced the burst release of TC from the bionanocomposites; and extended the antibacterial property of the samples up to two years. The melt mixing temperature was adjusted to a temperature lower than the melting point of LATC30 nanoparticles; therefore, these nanoparticles were dispersed in the PCL matrix without any chemical reaction and/or drug extraction. The sustained release behavior of TC from PCL remained unchanged since no significant changes occurred in the samples' crystallinity compared with that in the neat PCL. The elastic moduli of samples were enhanced once LATC30 is included. This is necessary since the elastic modulus is decreased with water absorption. The rheological behaviors of samples showed appropriate properties for melt electro-spinning. A stable process was established as the relaxation time of the bionanocomposites was increased. The hydrophilic properties of samples were increased with increasing LATC30. The proliferation rate of the fibroblast (L929) cells was enhanced as the content of nanoparticles was increased. A system similar to this could be implemented to prepare long-term antibacterial and drug delivery systems based on PCL and various low molecular weight drugs. The prepared bionanocomposites are considered as candidates for the soft connective tissue engineering and long-term drug delivery. PMID:27155590

  5. Cotton wool-like poly(lactic acid)/vaterite composite scaffolds releasing soluble silica for bone tissue engineering.

    PubMed

    Obata, Akiko; Ozasa, Hiroki; Kasuga, Toshihiro; Jones, Julian R

    2013-07-01

    Cotton wool-like poly(L-lactic acid) and siloxane-doped vaterite (SiV) composite scaffolds were prepared with a modified electrospinning system for bone tissue engineering applications. The effects of changing the SiV content in the materials from 10 to 30 wt% on elasticity and the ability to release calcium ions and soluble silica were evaluated. The elasticity of the cotton wool-like composites was almost the same as that of the PLLA from the results of compressibility and recovery tests. The materials released calcium ions for more than 56 days and soluble silica for 28-56 days in a tris buffer solution (pH 7.4). Mouse osteoblast-like cells (MC3T3-E1 cells) were cultured on/in the cotton wool-like materials or the fibremats out of the same composite materials as that used for the cotton wool-like materials. The cells penetrated into and proliferated inside the cotton wool-like materials, although they mainly adhered on the fibremat surface. PMID:23606191

  6. Evaluation of PEGylated exendin-4 released from poly (lactic-co-glycolic acid) microspheres for antidiabetic therapy.

    PubMed

    Lim, Sung Mook; Eom, Ha Na; Jiang, Hai Hua; Sohn, Minji; Lee, Kang Choon

    2015-01-01

    Peptide-based therapies have the potential to induce antibody formation if the molecules differ from a native human peptide. Several reports have disclosed the occurrence of antibody generation in a patient treated with exenatide. The immune response can be problematic from a clinical stand point, particularly if the antibodies neutralize the efficacy of the biotherapeutic agent or cause a general immune reaction. To overcome this limit, PEGylated exendin-4 analogs were designed and examined for metabolic stability and biological activity. To develop an extended release delivery system for exendin-4 for the safe and effective delivery of bioactive exendin-4 without peptide acylation and immunogenicity, PEGylated exendin-4 was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres by w/o/w double emulsion solvent evaporation method. Peptide-loaded microspheres were characterized in terms of morphology, particle diameter, and peptide encapsulation efficiency. Then, the release profile of the peptide from PLGA microspheres and the acylated products from PLGA polymer degradation was determined. The results obtained showed that the stability of exendin-4 was greatly improved by PEGylation. Moreover, eliminated acylation during PLGA polymer degradation in vitro and reduced immunogenicity in vivo were observed. The findings demonstrate that PEGylated exendin-4-loaded microspheres may be a safe and biocompatible system for clinical development. PMID:25407390

  7. Kupffer cells suppress perfluorononanoic acid-induced hepatic peroxisome proliferator-activated receptor α expression by releasing cytokines.

    PubMed

    Fang, Xuemei; Zou, Shanshan; Zhao, Yuanyuan; Cui, Ruina; Zhang, Wei; Hu, Jiayue; Dai, Jiayin

    2012-10-01

    Kupffer cells (KCs) have been demonstrated to play a role in the regulation of intra-hepatic lipid metabolism through the synthesis and secretion of biologically active products. The involvement of KCs in the disturbance of lipid metabolism that induced by perfluorononanoic acid (PFNA), a known agonist of the peroxisome proliferator-activated receptor alpha (PPARα), was investigated in this study. Rats were exposed to PFNA or PFNA combined with gadolinium chloride, an inhibitor of KCs, for 14 days. PFNA exposure dose-dependently increased absolute and relative liver weights, induced triglyceride accumulation, up-regulated the expression of both SERBP-1c and PPARα, and stimulated the release of TNFα and IL-1β. Inactivation of KCs markedly lowered TNFα and IL-1β level, enhanced PFNA-induced expression of PPARα and its target genes, and reduced liver triglyceride levels. In vitro, PFNA-induced expression of PPARα in primary cultured hepatocytes was suppressed by recombinant rat TNFα and IL-1β. However, inhibition of the NF-κB pathway prevented this. Transient transfection and promoter analysis further revealed that these two cytokines and NF-κB were coordinately involved in the suppression of PPARα promoter activity. Our data demonstrate that TNFα and IL-1β released from KCs following PFNA exposure can suppress the expression of PPARα via NF-κB pathway, which partially contribute to the evident accumulation of triglycerides in rat liver. PMID:22648072

  8. Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

    PubMed

    Xie, Tian; Taylor, Lynne S

    2016-03-01

    Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition. PMID:26791934

  9. Cellulose-nanofiber/polygalacturonic acid coatings with high oxygen barrier and targeted release properties.

    PubMed

    Mølgaard, Susanne L; Henriksson, Marielle; Cárdenas, Marité; Svagan, Anna J

    2014-12-19

    A bio-inspired coating consisting of pectin (polygalacturonic acid) and cationic cellulose nanofibers were successfully produced by the layer-by-layer method. The build-up and the morphology of the resulting coatings were studied with spectroscopic ellipsometry and atomic force microscopy, respectively. The coating was able to survive the exposure of a simulated gastric fluid, but was partially degraded upon exposure to pectinase enzyme, which simulate the action of the microbial symbionts present in the human colon. Prior to exposure, the oxygen permeability coefficient of the coating (0.033 ml(STP)mmm(-2)day(-1)atm(-1) at 23°C and 20% RH) was in the same order of magnitude as for ethylene vinyl alcohol films (0.001-0.01 ml(STP)mmm(-2)day(-1)atm(-1)). However, after exposure to the mimicked gastrointestinal (GI) tract conditions, the contribution of coating to the overall barrier properties was not measurable. PMID:25263879

  10. PEG-detachable and acid-labile cross-linked micelles based on orthoester linked graft copolymer for paclitaxel release

    NASA Astrophysics Data System (ADS)

    Yuan, Zhefan; Huang, Jingyi; Liu, Jing; Cheng, Sixue; Zhuo, Renxi; Li, Feng

    2011-08-01

    Polyethylene glycol detachable graft copolymer, mPEG-g-p(NAS-co-BMA), was synthesized by grafting 2-(ω-methoxy)PEGyl-1,3-dioxan-5-ylamine onto poly(N-(acryloyloxy)succinimide-co-butyl methacrylate). Pseudo in situ cross-linking of the mPEG-g-p(NAS-co-BMA) was performed in dimethylformamide phosphate buffer (v/v = 1/1) by an acid-labile diamine cross-linker bearing two symmetrical cyclic orthoesters. The cross-linked (CL) micelles with different contents of mPEG segments represented different morphologies. The CL micelles containing approximately one mPEG segment exhibited 'echini' morphology whereas the CL micelle with approximately three mPEG segments formed nanowires. The hydrolysis rate of the CL micelles is highly pH-dependent and much more rapid at mild acid than physiological conditions. Hydrolyzates of the CL micelles formed vesicles because new amphiphilic copolymers were formed. Paclitaxel (PTX) was successfully loaded into the CL micelles and a controlled and pH-dependent release behavior was observed. No obvious cytotoxicity was found for the CL micelles at concentration as high as 800 mg l - 1.

  11. Biogeochemical processes governing natural pyrite oxidation and release of acid metalliferous drainage.

    PubMed

    Chen, Ya-ting; Li, Jin-tian; Chen, Lin-xing; Hua, Zheng-shuang; Huang, Li-nan; Liu, Jun; Xu, Bi-bo; Liao, Bin; Shu, Wen-sheng

    2014-05-20

    The oxidative dissolution of sulfide minerals (principally pyrite) is responsible for the majority of acid metalliferous drainage from mine sites, which represents a significant environmental problem worldwide. Understanding the complex biogeochemical processes governing natural pyrite oxidation is critical not only for solving this problem but also for understanding the industrial bioleaching of sulfide minerals. To this end, we conducted a simulated experiment of natural pyrite oxidative dissolution. Pyrosequencing analysis of the microbial community revealed a distinct succession across three stages. At the early stage, a newly proposed genus, Tumebacillus (which can use sodium thiosulfate and sulfite as the sole electron donors), dominated the microbial community. At the midstage, Alicyclobacillus (the fifth most abundant genus at the early stage) became the most dominant genus, whereas Tumebacillus was still ranked as the second most abundant. At the final stage, the microbial community was dominated by Ferroplasma (the tenth most abundant genus at the early stage). Our geochemical and mineralogical analyses indicated that exchangeable heavy metals increased as the oxidation progressed and that some secondary sulfate minerals (including jarosite and magnesiocopiapite) were formed at the final stage of the oxidation sequence. Additionally, we propose a comprehensive model of biogeochemical processes governing the oxidation of sulfide minerals. PMID:24730689

  12. [Release of Extracellular DNA after Administration of Radioprotective Combination of α-Tocopherol and Ascorbic Acid].

    PubMed

    Vasilyeval, I N; Bespalov, V G

    2015-01-01

    Radioprotective and apoptotic activities of α-tocopherol acetate (vitamin E) and ascorbic acid (vitamin C) have been studied in 180 Wistar male rats. Rats were administered a single oral dose with vitamin E, vitamin C or their combination at prophylactic doses before or after the single whole body exposure to irradiation at the doses of 2 or 8 Gy. The radioprotective effect was evaluated by the frequency of chromosomal aberrations at metaphase plates of the bone marrow cells, apoptotic--by the level of circulating low-molecular-weight DNA (ImwDNA) in the blood plasma of irradiated rats. Administration of the combination of vitamins E and C before and after the irradiation at the dose of 2 Gy reduced the number of the cells with chromosomal aberrations thus providing the radioprotective effect, but separately administration of these vitamins did not show the significant radioprotective activity. Administration of the combination of vitamins E and C before irradiation with 8 Gy increased the lmwDNA in blood thus providing the apoptotic effect. So, synergy of radioprotective activities has been revealed in vitamins E and C action at prophylactic doses. Radioprotective effect of the combination of vitamins E and C can be associated with the apoptotic activity and can be explained by elimination of the least viable irradiated cells from the cell population. PMID:26863779

  13. Whey protein/polysaccharide-stabilized oil powders for topical application-release and transdermal delivery of salicylic acid from oil powders compared to redispersed powders.

    PubMed

    Kotzé, Magdalena; Otto, Anja; Jordaan, Anine; du Plessis, Jeanetta

    2015-08-01

    Oil-in-water (o/w) emulsions are commonly converted into solid-like powders in order to improve their physical and chemical stabilities. The aim of this study was to investigate whether whey protein/polysaccharide-stabilized o/w emulsions could be converted into stable oil powders by means of freeze-drying. Moreover, during this study, the effects of pH and polymer type on release and trans(dermal) delivery of salicylic acid, a model drug, from these oil powders were investigated and compared to those of the respective template emulsions and redispersed oil powders. Physical characterization of the various formulations was performed, such as droplet size analysis and oil leakage, and relationships drawn with regards to release and trans(dermal) delivery. The experimental outcomes revealed that the oil powders could be redispersed in water without changing the release characteristics of salicylic acid. pH and polymer type affected the release of salicylic acid from the oil powders, template emulsions, and redispersed powders similarly. Contrary, the transdermal delivery from the oil powders and from their respective redispersed oil powders was differently affected by pH and polymer type. It was hypothesized that the release had been influenced by the electrostatic interactions between salicylic acid and emulsifiers, whereas the transdermal performance could have been determined by the particle or aggregate sizes of the formulations. PMID:25573437

  14. Evidence that copper-amino acid complexes are potent stimulators of the release of luteinizing hormone-releasing hormone from isolated hypothalamic granules.

    PubMed

    Barnea, A; Cho, G

    1984-09-01

    Chelated copper has been previously shown to stimulate the release of LHRH from isolated hypothalamic granules. In this study, we evaluated the chelator specificity, the kinetic constants, and the characteristics of copper interaction with LHRH granules. LHRH granules were isolated from the median eminence area of adult male rats and then incubated in a buffered medium at 37 C. Release of LHRH into the incubation medium was assessed by RIA of LHRH remaining in the granules after incubation. It was found that CuHistidine (CuHis) as well as CuCysteine markedly stimulated LHRH release from the isolated granules, release being 56% and 63%, respectively, of the total LHRH content of granules incubated in buffer alone. In contrast, neither CuGly-His-Lys nor CuBSA stimulated LHRH release. The CuHis-stimulated release of LHRH was a saturable function of the concentration of CuHis. The Michaelis-Menten constants of this release process were estimated; the apparent Km for copper was found to be 4 microM, and the maximal velocity was 65% of the granule content of LHRH released in 5 min. In addition, we noted that CuHis-stimulated release of LHRH, assessed 6 min after CuHis, was completely abolished when dithiothreitol (DTT) was added immediately after CuHis, partially abolished when added 1 or 2 min after CuHis, and not affected at all when added 3 min after CuHis. This time course of DTT inhibition of LHRH release suggests that a period of 2-3 min of copper interaction with the granules is required for the 6-min manifestation of copper action. Furthermore, this DTT-inhibitable interaction of copper did not occur when granules were incubated at 4 C. In summary the findings that copper, chelated to putative circulating chelators, markedly stimulates LHRH release and that the apparent Km of 4 microM for copper in this process is within the concentration range for the physiological action of copper support the proposal that blood-borne copper can interact rapidly with the LHRH

  15. Pancreatic islet function in omega3 fatty acid-depleted rats: Glucose metabolism and nutrient-stimulated insulin release.

    PubMed

    Oguzhan, Berrin; Zhang, Ying; Louchami, Karim; Courtois, Philippe; Portois, Laurence; Chardigny, Jean-Michel; Malaisse, Willy J; Carpentier, Yvon A; Sener, Abdullah

    2006-06-01

    In order to gain information on the determinism of the perturbation of fuel homeostasis in situations characterized by a depletion in long-chain polyunsaturated omega3 fatty acids (omega3), the metabolic and hormonal status of omega3-depleted rats (second generation) was examined. When required, these rats were injected intravenously 120 min before sacrifice with a novel medium-chain triglyceride-fish oil emulsion able to provoke a rapid and sustained increase of the omega3 content in cell phospholipids. The measurement of plasma glucose, insulin, phospholipid, triglyceride, and unesterified fatty acid concentration indicated modest insulin resistance in the omega3-depleted rats. The plasma triglyceride and phospholipid concentrations were decreased in the omega3-depleted rats with abnormally low contribution of omega3 in both circulating and pancreatic islet lipids. The protein, insulin, and lipid content of the islets, as well as their intracellular and extracellular spaces, were little affected in the omega3-depleted rats. The metabolism of D-glucose in the islets of omega3-depleted rats was characterized by a lesser increase in D-[5-3H]glucose utilization and D-[U-14C]glucose oxidation in response to a given rise in hexose concentration and an abnormally low ratio between D-glucose oxidation and utilization. These abnormalities could be linked to an increased metabolism of endogenous fatty acids with resulting alteration of glucokinase kinetics. The release of insulin evoked by D-glucose, at a close-to-physiological concentration (8.3 mM), was increased in the omega3-depleted rats, this being considered as consistent with their insulin resistance. Relative to such a release, that evoked by a further rise in D-glucose concentration or by non-glucidic nutrients was abnormally high in omega3-depleted rats, and restored to a normal level after of the intravenous injection of the omega3-rich medium-chain triglyceride-fish oil emulsion. Because the latter procedure

  16. Ultrasound-triggered dual-drug release from poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers

    PubMed Central

    Song, Botao; Wu, Chengtie; Chang, Jiang

    2015-01-01

    The aim of this study was to achieve on-demand controlled drug release from the dual-drug-loaded poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers by the application of ultrasound irradiation. Two drugs were loaded in different part of the composite fibrous materials, and it was found that ultrasound as an external stimulus was able to control release of drugs due to both its thermal effect and non-thermal effect. With the selective irradiation of ultrasound, the drug carrier enabled to realize controlled release, and because of different location in fibers and sensitivity of two different kinds of drugs to ultrasound irradiation, the release rate of two drugs was different. These results indicated that ultrasound irradiation was a facile method to realize the on-demand controlled release of two drugs from the electrospun fibers. PMID:26816645

  17. Propofol differentially inhibits the release of glutamate, γ-aminobutyric acid and glycine in the spinal dorsal horn of rats

    PubMed Central

    Yang, Jing; Wang, Wei; Yong, Zheng; Mi, Weidong; Zhang, Hong

    2015-01-01

    Objective(s): Propofol (2, 6-diisopropylphenol) is an intravenous anesthetic that is commonly used for the general anesthesia. It is well known that the spinal cord is one of the working targets of general anesthesia including propofol. However, there is a lack of investigation of the effects of propofol on spinal dorsal horn which is important for the sensory transmission of nociceptive signals. The objective of this study was to investigate the effects of increasing dosage of propofol on the release of glutamate (Glu), γ-aminobutyric acid (GABA) and glycine (Gly) in the spinal dorsal horn. Materials and Methods: The efflux of Glu, GABA or Gly in the spinal dorsal horn of rats was detected using transverse spinal microdialysis under an awake condition and various depths of propofol anesthesia. The infusion rates of propofol were, in order, 400 µg/(kg·min), 600 µg/(kg·min) and 800 µg/(kg·min), with a 20 min infusion period being maintained at each infusion rate. Results: Propofol decreased the glutamate efflux within spinal dorsal horn in a dose-dependent manner, and the maximum decrease was 56.8 ± 6.0% at high-dose propofol infusion producing immobility. The inhibitory GABA and Gly efflux was also decreased about 15–20% at low-dose propofol infusion only producing sedation, but did not continue to drop with higher doses of propofol. Conclusion: Propofol decreased both excitatory and inhibitory amino acids efflux in spinal dorsal horn, and the preferential suppression of the excitatory amino acid might be associated with the analgesic effect of propofol. PMID:26557972

  18. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

    SciTech Connect

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. )

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

  19. Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

    PubMed

    Wulff, R; Rappen, G-M; Koziolek, M; Garbacz, G; Leopold, C S

    2015-09-18

    The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs. PMID:26093053

  20. Phenylboronic Acid Appended Pyrene-Based Low-Molecular-Weight Injectable Hydrogel: Glucose-Stimulated Insulin Release.

    PubMed

    Mandal, Deep; Mandal, Subhra Kanti; Ghosh, Moumita; Das, Prasanta Kumar

    2015-08-17

    A pyrene-containing phenylboronic acid (PBA) functionalized low-molecular-weight hydrogelator was synthesized with the aim to develop glucose-sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8-12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL(-1) . The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π-π stacking, and van der Waals interactions are the key factors for the self-assembled gelation. The diol-sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose-responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose-induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin-loaded hydrogel showed thixotropic self-recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells. PMID:26184777

  1. Identification of iopanoic acid as substrate of type 1 deiodinase by a novel nonradioactive iodide-release assay.

    PubMed

    Renko, Kostja; Hoefig, Carolin S; Hiller, Franziska; Schomburg, Lutz; Köhrle, Josef

    2012-05-01

    Enzymatic 5'- and 5-deiodination are key reactions for local and systemic activation and inactivation of iodothyronines and thyronamines. Expression of the three deiodinase (DIO) isoenzymes is regulated by a number of parameters, including thyroid status, genotype, micronutrient availability, and disease-related signaling. In addition, DIO are potential targets of pharmacological as well as environmentally derived substances, which might affect their enzymatic activity (endocrine disruptors). With the classical DIO activity assay, testing depends on the availability of radioactively labeled substrates (e.g. (125)I-rT(3)) to monitor the release of radioactive iodide. Recently, liquid chromatography-tandem mass spectrometry was described as an alternative method apparently resolving this limitation. However, it has a high demand in technical equipment and analytical routine and is limited in sample number by considerable measuring time. We therefore combined the classical deiodination assay with an easily accessible photometric method taking advantage of the Sandell-Kolthoff reaction for measuring iodide release. In brief, iodine works as a catalyst within this redox reaction between Ce(4+) and As(3+) leading to an acceleration of destaining. Furthermore, the protocol was adapted to minimize handling effort and time consumption. Because this method is not dependent on radioactivity, it expands the substrate spectrum of the classical method. Suitability of this assay was tested with tissue samples from animal experiments (hepatic Dio1 activity in hypo- and hyperthyroid mice) and established DIO inhibitors. As a new but not unexpected finding, the alleged inhibitor iopanoic acid turned out to be a DIO substrate. This finding was confirmed by liquid chromatography-tandem mass spectrometry, and its potential clinical impact requires further studies. PMID:22434082

  2. Regional release of [3H]adenosine derivatives from rat brain in vivo: effect of excitatory amino acids, opiate agonists, and benzodiazepines.

    PubMed

    Jhamandas, K; Dumbrille, A

    1980-11-01

    Previous studies have suggested that the theophylline-sensitive actions of (a) glutamic acid and related excitatory amino acids, (b) opiate agonists, and (c) benzodiazepines may be mediated by adenosine and its derivatives (AD). In this study the effects of these theophylline-sensitive agents on the in vivo release of labelled AD from the rat cerebral cortex and cerebellum were examined. Application of L-glutamate (L-Glu) to the cortex or cerebellum, preloaded with [3H]adenosine or [3H]adenine, markedly stimulated the release of [3H]adenosine derivatives ([3H]AD) from these regions. This effect was also produced by L-aspartate (L-Asp), kainate (Kai), and two "non-amino-acid" depolarizing agents, veratridine and potassium (56 mM). In the cerebral cortex the excitatory action of L-Glu or L-Asp was stronger than that of Kai but in the cerebellum all of these agents produced a similar effect on the release of [3H]AD. Pretreatment of the cortex with glutamic acid diethylester, HA966, 2-amino-4-phosphonobutyrate, and 2,3-diaminopropionate, but not theophylline, selectively antagonized the releasing action of L-Glu. This action of L-Glu was also reduced by EGTA added to a Ca-free physiological medium. In the cortex and cerebellum the excitatory action of L-Glu on the release of [3H]AD was attenuated by tetrodotoxin (TTX). TTX also antagonized the action of veratridine, but not potassium, on the cortical output of [3H]AD. Chromatographic analysis of release samples showed that about 60% of the total radioactivity released by L-Glu was associated with pharmacologically active AD, adenosine, and adenine nucleotides. The opiate agonists morphine and D-Met2-Pro5-enkephalinamide by themselves did not influence the spontaneous release of [3H]AD from the cortex but both agents very effectively inhibited the release evoked by L-Glu. This inhibitory action was antagonized by naloxone. At a low dose levorphanol, but not dextrorphan, inhibited the L-Glu-evoked release of [3H]AD. Both

  3. Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

    PubMed Central

    Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

    2011-01-01

    Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

  4. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release.

    PubMed

    Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

    2015-01-01

    Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. PMID:26351630

  5. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release

    PubMed Central

    Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

    2015-01-01

    Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. PMID:26351630

  6. Potential of a cryopreserved cultured dermal substitute composed of hyaluronic acid and collagen to release angiogenic cytokine.

    PubMed

    Sawa, Manami; Kuroyanagi, Yoshimitsu

    2013-01-01

    An allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts on a spongy matrix of hyaluronic acid (HA) and collagen (Col), which was then cryopreserved. This cryopreserved allogeneic CDS (CDS-1; cryopreserved for 1 month, CDS-6; cryopreserved for 6 months) was thawed and re-cultured for a period of 7 days to investigate the potential of the CDS for wound treatment. The cell metabolic activity in the CDS and their cytokine production were measured using an MTT assay and ELISA. Fibroblast metabolic activity in each CDS-1 and CDS-6 immediately after thawing and following 3 and 7 days of re- cultivation was 56, 67 and 93%, and 49, 64 and 86%, respectively, of that before cryopreservation. The amount of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) released from the CDS-1 on days 1, 3 and 7 of re-cultivation after thawing was 8, 44 and 92% (VEGF) and 3, 7 and 28% (HGF), respectively, of that before cryopreservation. The amount of VEGF and HGF released from the CDS-6 on days 1, 3 and 7 of re-cultivation after thawing was 9, 32 and 45% (VEGF) and 6, 10 and 27% (HGF), respectively, of that before cryopreservation. These findings showed that the potential of the CDS was restored to some extent over the first 3 days of re-cultivation after thawing. The potential of the CDS for wound treatment was then evaluated using a wound surface model, in which the each CDS-1 and CDS-6 that was re-cultured for 3 days after thawing was elevated at the air/culture medium interface, and a wound dressing was placed on top, and then cultured for 5 days. Two different types of wound dressing were tested. Fibroblasts in the CDS in Group II (placing a wound dressing with EGF) released increased amount of VEGF and HGF compared with that in Group I (placing a wound dressing without EGF). These findings suggest that re-culture of the CDS for 3 days following thawing results in a CDS with improved wound healing potential and that an EGF

  7. Systemic bile acid sensing by G protein-coupled bile acid receptor 1 (GPBAR1) promotes PYY and GLP-1 release

    PubMed Central

    Ullmer, C; Alvarez Sanchez, R; Sprecher, U; Raab, S; Mattei, P; Dehmlow, H; Sewing, S; Iglesias, A; Beauchamp, J; Conde-Knape, K

    2013-01-01

    Background and Purpose Nutrient sensing in the gut is believed to be accomplished through activation of GPCRs expressed on enteroendocrine cells. In particular, L-cells located predominantly in distal regions of the gut secrete glucagon-like peptide 1 (GLP-1) and peptide tyrosine-tyrosine (PYY) upon stimulation by nutrients and bile acids (BA). The study was designed to address the mechanism of hormone secretion in L-cells stimulated by the BA receptor G protein-coupled bile acid receptor 1 (GPBAR1). Experimental Approach A novel, selective, orally bioavailable, and potent GPBAR1 agonist, RO5527239, was synthesized in order to investigate L-cell secretion in vitro and in vivo in mice and monkey. In analogy to BA, RO5527239 was conjugated with taurine to reduce p.o. bioavailability yet retaining its potency. Using RO5527239 and tauro-RO5527239, the acute secretion effects on L-cells were addressed via different routes of administration. Key Results GPBAR1 signalling triggers the co-secretion of PYY and GLP-1, and leads to improved glucose tolerance. The strong correlation of plasma drug exposure and plasma PYY levels suggests activation of GPBAR1 from systemically accessible compartments. In contrast to the orally bioavailable agonist RO5527239, we show that tauro-RO5527239 triggers PYY release only when applied intravenously. Compared to mice, a slower and more sustained PYY secretion was observed in monkeys. Conclusion and Implications Selective GPBAR1 activation elicits a strong secretagogue effect on L-cells, which primarily requires systemic exposure. We suggest that GPBAR1 is a key player in the intestinal proximal-distal loop that mediates the early phase of nutrient-evoked L-cell secretion effects. PMID:23488746

  8. Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging

    PubMed Central

    Isaac, Vera Lucia Borges; Chiari-Andréo, Bruna Galdorfini; Marto, Joana Marques; Moraes, Jemima Daniela Dias; Leone, Beatriz Alves; Corrêa, Marcos Antonio; Ribeiro, Helena Margarida

    2015-01-01

    The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and the in vitro release profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA. PMID:26788510

  9. Evaluation of an extended-release formulation of ceftiofur crystalline-free acid in koi (Cyprinus carpio).

    PubMed

    Grosset, C; Weber, E S; Gehring, R; Sanchez-Migallon Guzman, D; Campbell, L A; Enz, C; Groff, J M; Tell, L A

    2015-12-01

    The use of an extended release ceftiofur crystalline-free acid formulation (CCFA, Excede For Swine(®) , Pfizer Animal Health) in koi was evaluated after administration of single intramuscular (i.m.) or intracoelomic (i.c.) doses. Twenty koi were divided randomly into a control group and four treatment groups (20 mg/kg i.m., 60 mg/kg i.m., 30 mg/kg i.c., and 60 mg/kg i.c.). Serum ceftiofur-free acid equivalents (CFAE) concentrations were quantified. The pharmacokinetic data were analyzed using a nonlinear mixed-effects approach. Following a CCFA injection of 60 mg/kg i.m., time durations that serum CFAE concentrations were above the target concentration of 4 μg/mL ranged from 0.4 to 2.5 weeks in 3 of 4 fish, while serum CFAE concentrations remained below 4 μg/mL for lower doses evaluated. Substantial inter-individual variations and intra-individual fluctuations of CFAE concentrations were observed for all treatment groups. Histological findings following euthanasia included aseptic granulomatous reactions, but no systemic adverse effects were detected. Given the unpredictable time vs. CFAE concentration profiles for treated koi, the authors would not recommend this product for therapeutic use in koi at this time. Further research would be necessary to correlate serum and tissue concentrations and to better establish MIC data for Aeromonas spp. isolated from naturally infected koi. PMID:25876672

  10. NUTRIENT RELEASE FROM CONTROLLLED-RELEASE FERTILIZERS IN ACID SUBSTRATE IN A GREENHOUSE ENVIRONMENT: II.LEACHATE CALCIUM, MAGNESIUM, IRON MANGANESE, ZINC, COPPER, AND MOLYBDENUM CONCENTRATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leachate from containerized substrate containing one of four different controlled-release fertilizers (Osmocote, Nutricote, Polyon, or Multicote) were monitored for concentrations of Ca, Mg, Fe, Mn, Zn, Cu and Mo during a 47-week period. Environmental and cultural practices simulated an unheated gr...

  11. Salicylic acid-based poly(anhydride-ester) nerve guidance conduits: Impact of localized drug release on nerve regeneration.

    PubMed

    Lee, Yong S; Griffin, Jeremy; Masand, Shirley N; Shreiber, David I; Uhrich, Kathryn E

    2016-04-01

    Nerve guidance conduits (NGCs) can serve as physical scaffolds aligning and supporting regenerating cells while preventing scar tissue formation that often interferes with the regeneration process. Numerous studies have focused on functionalizing NGCs with neurotrophic factors, for example, to support nerve regeneration over longer gaps, but few directly incorporate therapeutic agents. Herein, we fabricated NGCs from a polyanhydride comprised of salicylic acid (SA), a nonsteroidal anti-inflammatory drug, then performed in vitro and in vivo assays. In vitro studies included cytotoxicity, anti-inflammatory response, and NGC porosity measurements. To prepare for implantation, type I collagen hydrogels were used as NGC luminal fillers to further enhance the axonal regeneration process. For the in vivo studies, SA-NGCs were implanted in femoral nerves of mice for 16 weeks and evaluated for functional recovery. The SA-based NGCs functioned as both a drug delivery vehicle capable of reducing inflammation and scar tissue formation because of SA release as well as a tissue scaffold that promotes peripheral nerve regeneration and functional recovery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 975-982, 2016. PMID:26691691

  12. Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

    PubMed

    Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

    2016-08-20

    In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. PMID:27178954

  13. Environmental Nitrate Stimulates Abscisic Acid Accumulation in Arabidopsis Root Tips by Releasing It from Inactive Stores[OPEN

    PubMed Central

    2016-01-01

    Abscisic acid (ABA) signaling plays a major role in root system development, regulating growth and root architecture. However, the precise localization of ABA remains undetermined. Here, we present a mechanism in which nitrate signaling stimulates the release of bioactive ABA from the inactive storage form, ABA-glucose ester (ABA-GE). We found that ABA accumulated in the endodermis and quiescent center of Arabidopsis thaliana root tips, mimicking the pattern of SCARECROW expression, and (to lower levels) in the vascular cylinder. Nitrate treatment increased ABA levels in root tips; this stimulation requires the activity of the endoplasmic reticulum-localized, ABA-GE-deconjugating enzyme β-GLUCOSIDASE1, but not de novo ABA biosynthesis. Immunogold labeling demonstrated that ABA is associated with cytoplasmic structures near, but not within, the endoplasmic reticulum. These findings demonstrate a mechanism for nitrate-regulated root growth via regulation of ABA accumulation in the root tip, providing insight into the environmental regulation of root growth. PMID:26887919

  14. Electrochemical immunosensor for detection of prostate specific antigen based on an acid cleavable linker into MSN-based controlled release system.

    PubMed

    Fan, Dawei; Li, Na; Ma, Hongmin; Li, Yan; Hu, Lihua; Du, Bin; Wei, Qin

    2016-11-15

    A mesoporous silica nanoparticle (MSN)-based controlled release system with acid cleavable linkage was developed to fabricate an electrochemical immunosensor for the quantitative detection of the prostate-specific antigen (PSA). 3,9-Bis(3-aminopropyl)-2,4,8,10-tetraoxaspiro[5.5]undecane functionalized mesoporous silica nanoparticles (MSN-Acetal) were used to immobilize the electron mediator thionine (Th). The encapsulation of Th molecules was achieved by capping the pores of MSN-Acetal with carboxylic acid modified Au nanoparticles (defined as MSN-Th-Au). Under the acidic conditions, the capped Au nanoparticles were removed from MSN-Th-Au through the hydrolysis of the acid-labile acetal linker, resulting in the release of encapsulated Th. In this work, the pH-responsive cargo release system was firstly used as the label of secondary anti-PSA for developing an electrochemical immunosensor, and amination Fe3O4 was used as the sensing matrix for immobilizing primary anti-PSA on magnetic carbon electrode surfaces. The specific recognition of PSA resulted in the attachment of MSN-Th-Au-secondary anti-PSA (MSN-Th-Au-Ab2) onto the electrode surfaces. Subsequently, the released Th was detected by differential pulse voltammetry under the acidic conditions. The developed cargo release system provided an innovative and reliable method for the detection of PSA because the response signal was correlated with the concentration of PSA. Under the optimal conditions, the electrochemical immunosensor exhibited a wide linear range of 0.001-5.0ng/mL with a low detection limit of 0.31pg/mL. Moreover, the developed immunosensor showed superior reproducibility and long-term stability, which has promising applications in bioassay and biosensing. PMID:27236723

  15. Electrically induced release of amino acids formed from (U14C) glucose in rat brain cortex slices, studied by a simplified dansylation procedure.

    PubMed

    Orrego, F; Doria de Lorenzo, M C

    1980-05-01

    The nonessential amino acids glutamate, aspartate, glutamine, gamma-aminobutyrate (GABA), alanine, glycine, and proline present in rat thin brain cortex slices were labeled by in vitro incubation of these with [U-14C]glucose, and the efflux of such endogenous radioactive amino acids and of lactate was studied in a superfused system, under control conditions or when the slices were depolarized by varous procedures. When electrical stimuli known to induce selective neurotransmitter release (1 or 1.5 volt, sine wave 60 Hz) were applied for 10 sec to the slices, no significant increase in amino acid efflux was found. When more intense stimuli (4 volt, 60 Hz) were applied for 60 sec, or extracellular potassium was raised to 56 mM, both conditions being known to induce nonselective substance release, the efflux of essentially all amino acids and of lactate was markedly increased. Increases in efflux were proportionately larger for glutamate, aspartate, and gamma-aminobutyrate, and this could be accounted for by their greater intracellular chemical (or electrochemical) potentials, but not because of a selective release mechanism for them. Amino acids were analyzed as their 1-dimethylaminoaphthalene-5-sulfonyl (dansyl) derivatives, by a modification of existing procedures in which the dansyl (DNS) derivatives were efficiently extracted from acidified incubation fluid into an organic phase. This rapidly desalted the derivatives and allowed their concentration and chromatographic separation on thin-layer silica gel sheets with little loss. PMID:7393382

  16. Peptide Synthesis through Cell-Free Expression of Fusion Proteins Incorporating Modified Amino Acids as Latent Cleavage Sites for Peptide Release.

    PubMed

    Liutkus, Mantas; Fraser, Samuel A; Caron, Karine; Stigers, Dannon J; Easton, Christopher J

    2016-05-17

    Chlorinated analogues of Leu and Ile are incorporated during cell-free expression of peptides fused to protein, by exploiting the promiscuity of the natural biosynthetic machinery. They then act as sites for clean and efficient release of the peptides simply by brief heat treatment. Dehydro analogues of Leu and Ile are similarly incorporated as latent sites for peptide release through treatment with iodine under cold conditions. These protocols complement enzyme-catalyzed methods and have been used to prepare calcitonin, gastrin-releasing peptide, cholecystokinin-7, and prolactin-releasing peptide prohormones, as well as analogues substituted with unusual amino acids, thus illustrating their practical utility as alternatives to more traditional chemical peptide synthesis. PMID:26918308

  17. Branched Chain Amino Acids Induce Apoptosis in Neural Cells without Mitochondrial Membrane Depolarization or Cytochrome c Release: Implications for Neurological Impairment Associated with Maple Syrup Urine Disease

    PubMed Central

    Jouvet, Philippe; Rustin, Pierre; Taylor, Deanna L.; Pocock, Jennifer M.; Felderhoff-Mueser, Ursula; Mazarakis, Nicholas D.; Sarraf, Catherine; Joashi, Umesh; Kozma, Mary; Greenwood, Kirsty; Edwards, A. David; Mehmet, Huseyin

    2000-01-01

    Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain α-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular α-keto isocaproic acid, specifically induced apoptosis in glial and neuronal cells in culture. Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, α-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their α-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway. PMID:10793161

  18. Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits

    PubMed Central

    Rui, Jing; Dadsetan, Mahrokh; Runge, M. Brett; Spinner, Robert J.; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of VEGF encapsulating poly-lactic-co-glycolic acid (PLGA) microspheres and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of the microspheres with a diameter < 53 µm. VEGF content measured by ELISA indicated 93.79 ±10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6±8.25% within the first 24 hours, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation confirming that VEGF retained its bioactivity through the 4-week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold, robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system. PMID:22019759

  19. Effects of Cortex Peptidoglycan Structure and Cortex Hydrolysis on the Kinetics of Ca2+-Dipicolinic Acid Release during Bacillus subtilis Spore Germination

    PubMed Central

    Zhang, Pengfei; Thomas, Stacy; Li, Yong-qing

    2012-01-01

    The kinetic parameters of the release of Ca2+-dipicolinic acid (CaDPA) during germination of spore populations and multiple individual spores of Bacillus subtilis strains with major alterations in the structure of the spore peptidoglycan (PG) cortex or lacking one or both of the two redundant enzymes involved in cortex hydrolysis (cortex-lytic enzymes [CLEs]) were determined. The lack of the CLE CwlJ greatly slowed CaDPA release with a germinant receptor (GR)-dependent germinant, l-valine, or a non-GR-dependent germinant, dodecylamine. The absence of the cortex-specific PG modification muramic acid–δ-lactam also increased the time needed for full CaDPA release during germination with both types of germinants. In contrast, increased cortex PG cross-linking was associated with faster times for initiation of CaDPA release with both l-valine and dodecylamine but not with faster CaDPA release once this release had been initiated. These data suggest that the precise structure of the spore cortex plays a significant role in determining the timing and the rate of CaDPA release during B. subtilis spore germination and, further, that this effect is independent of effects of GRs. PMID:22123250

  20. Acid rain report released

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    A joint report issued January 8, 1986, by special envoys from the United States and Canada recommends that the United States implement a 5-year, $5-billion commercial demonstration program for technologies to control emissions from the burning of coal. The recommendations call for government and industry to share the costs of the proposed program.The report was issued by Drew Lewis, former U.S. Secretary of Transportation, and William Davis, former Premier of Ontario, at the request of U.S. President Ronald Reagan and Canadian Prime Minister Brian Mulroney after a summit conference between the two leaders in March 1985. Discussion of the report is on the agenda for a second meeting this coming March. Reagan has said he will review the report but has not committed himself to endorse its recommendations.

  1. The effects of the oral administration of fish oil concentrate on the release and the metabolism of (/sup 14/C)arachidonic acid and (/sup 14/C)eicosapentaenoic acid by human platelets

    SciTech Connect

    Hirai, A.; Terano, T.; Hamazaki, T.; Sajiki, J.; Kondo, S.; Ozawa, A.; Fujita, T.; Miyamoto, T.; Tamura, Y.; Kumagai, A.

    1982-11-01

    It has been suggested by several investigators that eicosapentaenoic acid (C20:5 omega 3, EPA) might have anti-thrombotic effects. In this experiment, the effect of the oral administration of EPA rich fish oil concentrate on platelet aggregation and the release and the metabolism of (/sup 1 -14/C)arachidonic acid and ((U)-/sup 14/C)eicosapentaenoic acid by human platelets was studied. Eight healthy male subjects ingested 18 capsules of fish oil concentrate (EPA 1.4 g) per day for 4 weeks. Plasma and platelet concentrations of EPA markedly increased, while those of arachidonic acid (C20:4 omega 6, AA) and docosahexaenoic acid (C22:6 omega 3, DHA) did not change. Platelet aggregation induced by collagen and ADP was reduced. Collagen induced (/sup 14/C)thromboxane B2 (TXB2) formation from (/sup 14/C)AA prelabeled platelets decreased. There was no detectable formation of (/sup 14/C)TXB3 from (/sup 14/C)EPA prelabeled platelets, and the conversion of exogenous (/sup 14/C)EPA to (/sup 14/C)TXB3 was lower than that of (/sup 14/C)AA to (/sup 14/C)TXB2. The release of (/sup 14/C)AA from (/sup 14/C)AA prelabeled platelets by collagen was significantly decreased. These observations raise the possibility that the release of arachidonic acid from platelet lipids might be affected by the alteration of EPA content in platelets.

  2. Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

    SciTech Connect

    Arslan, M.; Rizvi, S.S.R.; Jahan, S.; Zaidi, P.; Shahab, M. )

    1991-01-01

    N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.

  3. A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin.

    PubMed

    Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R; Khan, Haseeb A; Cho, Kwang Jae; Lee, Yong-kyu

    2015-06-28

    The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK). PMID:26030737

  4. Surface-Deacetylated Chitin Nano-Fiber/Hyaluronic Acid Composites as Potential Antioxidative Compounds for Use in Extended-Release Matrix Tablets

    PubMed Central

    Anraku, Makoto; Tabuchi, Ryo; Ifuku, Shinsuke; Ishiguro, Takako; Iohara, Daisuke; Hirayama, Fumitoshi

    2015-01-01

    In this study, we examined a possible use of a surface-deacetylated chitin nano-fiber (SDCH-NF) and hyaluronic acid (HA) interpolymer complex (IPC) tablet as a potential antioxidative compound in extended-release matrix tablets. The antioxidant properties of untreated chitin (UCH), SDCH-NF, and HA were examined using N-centered radicals derived from 1,1′-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). SDCH-NF and HA had acceptable scavenging abilities and were relatively efficient radical scavengers, but UCH was much less effective. The results suggest that SDCH-NF and HA could serve as scavengers of compounds related to the development of oxidative stress. An SDCH-NF/HA IPC tablet was prepared and evaluated as an extended-release tablet matrix using famotidine (FMT) as a model drug. The release of FMT from the IPC tablet (DCF-NF:HA = 1:1) was slower than that from a SDCH-NF only tablet. Turbidity measurements and X-ray diffraction (XRD) data also indicated that the optimum complexation ratio for IPC between SDCH-NF/HA is 1/1, resulting in a good relationship between turbidity or XRD of the complex and the release ratio of FMT. These results suggest that an SDCH-NF/HA tablet has the potential for use in an extended-release IPC tablet with a high antioxidant activity. PMID:26501272

  5. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    PubMed

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland. PMID:27052215

  6. Gastric acid induces mucosal H2S release in rats by upregulating mRNA and protein expression of cystathionine gamma lyase.

    PubMed

    Mard, Seyyed Ali; Veisi, Ali; Ahangarpour, Akram; Gharib-Naseri, Mohammad Kazem

    2015-11-01

    It is well known that hydrogen sulfide (H2S) protects the gastric mucosa against gastric acid and other noxious stimulants by several mechanisms but until now the effect of gastric acid on H2S production has not been evaluated. This study was performed to determine the effect of basal and stimulated gastric acid secretion on mRNA and protein expression of cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), and on mucosal release of H2S in rats. Seventy-two male rats were randomly assigned into 9 groups (8 in each)-control, distention, and pentagastrin-induced gastric acid secretion groups. The effects of 15% alcohol solution, propargylglycine (PAG), L-NAME, and pantoprazole were also investigated. Under anesthesia, animals underwent tracheostomy and midline laparotomy. A catheter was inserted into the stomach through the duodenum for gastric washout. At the end of the experiments, the animals were killed and the gastric mucosa was collected to measure H2S concentration and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR, and expression of their proteins by western blot. Basal and stimulated gastric acid secretion increased mucosal levels of H2S, and mRNA and protein expression of CSE. Pantoprazole and L-NAME reversed H2S release and restored protein expression of CSE to the control level. Pantoprazole, but not propargylglycine, pretreatment inhibited the elevated level of protein expression of eNOS in response to distention-induced gastric acid secretion. Our findings indicated that NO mediated the stimulatory effect of gastric acid on H2S release and protein expression of CSE. PMID:26319795

  7. Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents

    PubMed Central

    Lee, Cheng-Hung; Yu, Chia-Ying; Chang, Shang-Hung; Hung, Kuo-Chun; Liu, Shih-Jung; Wang, Chao-Jan; Hsu, Ming-Yi; Hsieh, I-Chang; Chen, Wei-Jan; Ko, Yu-Shien; Wen, Ming-Shien

    2014-01-01

    Introduction This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel. Methods To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning. Results Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels. Conclusion The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries. PMID:25206303

  8. Ethanesulfohydroxamic acid ester prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs): synthesis, nitric oxide and nitroxyl release, cyclooxygenase inhibition, anti-inflammatory, and ulcerogenicity index studies.

    PubMed

    Huang, Zhangjian; Velázquez, Carlos A; Abdellatif, Khaled R A; Chowdhury, Morshed A; Reisz, Julie A; DuMond, Jenna F; King, S Bruce; Knaus, Edward E

    2011-03-10

    The carboxylic acid group of the anti-inflammatory (AI) drugs indo-methacin, (S)-naproxen and ibuprofen was covalently linked via a two-carbon ethyl spacer to a sulfohydroxamic acid moiety (CH(2)CH(2)SO(2)NHOH) to furnish a group of hybrid ester prodrugs that release nitric oxide (NO) and nitroxyl (HNO). Biological data acquired for this hitherto unknown class of ethanesulfohydroxamic acid ester prodrugs showed (i) all compounds exhibited superior NO, but similar HNO, release properties relative to arylsulfohydroxamic acids, (ii) the (S)-naproxen and ibuprofen prodrug esters are more potent AI agents than their parent NSAID, (iii) the indomethacin prodrug ester, in contrast to indomethacin which is highly ulcerogenic, showed no visible stomach lesions [ulcer index (UI) = 0 for a 80 μmol/kg oral dose] while retaining potent AI activity, and iv) that the indomethacin prodrug ester, unlike indomethacin which is an ulcerogenic selective COX-1 inhibitor, is a selective COX-2 inhibitor (COX-2 selectivity index = 184) devoid of ulcerogenicity that is attributed to its high COX-2 SI and/or ability to release cytoprotective NO. PMID:21280601

  9. Redox buffered hydrofluoric acid etchant for the reduction of galvanic attack during release etching of MEMS devices having noble material films

    DOEpatents

    Hankins, Matthew G.

    2009-10-06

    Etchant solutions comprising a redox buffer can be used during the release etch step to reduce damage to the structural layers of a MEMS device that has noble material films. A preferred redox buffer comprises a soluble thiophosphoric acid, ester, or salt that maintains the electrochemical potential of the etchant solution at a level that prevents oxidation of the structural material. Therefore, the redox buffer preferentially oxidizes in place of the structural material. The sacrificial redox buffer thereby protects the exposed structural layers while permitting the dissolution of sacrificial oxide layers during the release etch.

  10. LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes

    PubMed Central

    Hyzinski-García, María C; Rudkouskaya, Alena; Mongin, Alexander A

    2014-01-01

    In mammals, cellular swelling activates release of small organic osmolytes, including the excitatory amino acids (EAA) glutamate and aspartate, via a ubiquitously expressed volume-regulated chloride/anion channel (VRAC). Pharmacological evidence suggests that VRAC plays plural physiological and pathological roles, including excitotoxic release of glutamate in stroke. However, the molecular identity of this pathway was unknown. Two recent studies discovered that LRRC8 gene family members encode heteromeric VRAC composed of LRRC8A plus LRRC8B-E, which mediate swelling-activated Cl− currents and taurine release in human non-neural cells (Z. Qiu et al. Cell 157: 447, 2014; F.K. Voss et al. Science 344: 634, 2014). Here, we tested the contribution of LRRC8A to the EAA release in brain glia. We detected and quantified expression levels of LRRC8A-E in primary rat astrocytes with quantitative RT-PCR and then downregulated LRRC8A with gene-specific siRNAs. In astrocytes exposed to hypo-osmotic media, LRRC8A knockdown dramatically reduced swelling-activated release of the EAA tracer d-[3H]aspartate. In parallel HPLC assays, LRRC8A siRNA prevented hypo-osmotic media-induced loss of the endogenous intracellular l-glutamate and taurine. Furthermore, downregulation of LRRC8A completely ablated the ATP-stimulated release of d-[3H]aspartate and [14C]taurine from non-swollen astrocytes. Overall, these data indicate that LRRC8A is an indispensable component of a permeability pathway that mediates both swelling-activated and agonist-induced amino acid release in brain glial cells. PMID:25172945

  11. Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

    PubMed

    Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

    2016-03-01

    Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. PMID:26774005

  12. Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury.

    PubMed

    Khalaf, Aseel; Babiker, Fawzi

    2016-09-01

    We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I

  13. The release of dipicolinic acid--the rate-limiting step of Bacillus endospore inactivation during the high pressure thermal sterilization process.

    PubMed

    Reineke, Kai; Schlumbach, Karl; Baier, Daniel; Mathys, Alexander; Knorr, Dietrich

    2013-03-01

    High pressure combined with elevated temperatures can produce low acid, commercially sterile and shelf-stable foods. Depending on the temperature and pressure levels applied, bacterial endospores pass through different pathways, which can lead to a pressure-induced germination or inactivation. Regardless of the pathway, Bacillus endospores first release pyridine-2,6-dicarboxylic acid (DPA), which contributes to the low amount of free water in the spore core and is consequently responsible for the spore's high resistance against wet and dry heat. This is therefore the rate-limiting step in the high pressure sterilization process. To evaluate the impact of a broad pressure, temperature and time domain on the DPA release, Bacillus subtilis spores were pressure treated between 0.1 and 900 MPa at between 30 and 80 °C under isothermal isobaric conditions during dwell time. DPA quantification was assessed using HPLC, and samples were taken both immediately and 2 h after the pressure treatment. To obtain a release kinetic for some pressure-temperature conditions, samples were collected between 1s and 60 min after decompression. A multiresponse kinetic model was then used to derive a model covering all kinetic data. The isorate lines modeled for the DPA release in the chosen pressure-temperature landscape enabled the determination of three distinct zones. (I) For pressures <600 MPa and temperatures >50 °C, a 90% DPA release was achievable in less than 5 min and no difference in the amount of DPA was found immediately 2 h after pressurization. This may indicate irreversible damage to the inner spore membrane or membrane proteins. (II) Above 600 MPa the synergism between pressure and temperature diminished, and the treatment temperature alone dominated DPA release. (III) Pressures <600 MPa and temperatures <50 °C resulted in a retarded release of DPA, with strong increased differences in the amount of DPA released after 2 h, which implies a pressure-induced physiological

  14. In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere

    PubMed Central

    Xiong, Yan; Yu, Zeping; Lang, Yun; Hu, Juanyu; Li, Hong; Yan, Yonggang; Tu, Chongqi; Yang, Tianfu; Song, Yueming; Duan, Hong; Pei, Fuxing

    2016-01-01

    Objective To study the degradation and basic fibroblast growth factor (bFGF) release activity of bFGF – poly(lactic-co-glycolic-acid) microsphere (bFGF-PLGA MS) under stress in vitro, including the static pressure and shearing force-simulating mechanical environment of the joint cavity. Method First, bFGF-PLGA MSs were created. Meanwhile, two self-made experimental instruments (static pressure and shearing force loading instruments) were initially explored to provide stress-simulating mechanical environment of the joint cavity. Then, bFGF-PLGA MSs were loaded into the two instruments respectively, to study microsphere degradation and drug release experiments. In the static pressure loading experiment, normal atmospheric pressure loading (approximately 0.1 MPa), 0.35 MPa, and 4.0 MPa pressure loading and shaking flask oscillation groups were designed to study bFGF-PLGA MS degradation and bFGF release. In the shearing force loading experiment, a pulsating pump was used to give the experimental group an output of 1,000 mL/min and the control group an output of 10 mL/min to carry out bFGF-PLGA MS degradation and drug release experiments. Changes of bFGF-PLGA MSs, including microsphere morphology, quality, weight-average molecular weight of polymer, and microsphere degradation and bFGF release, were analyzed respectively. Results In the static pressure loading experiment, bFGF-PLGA MSs at different pressure were stable initially. The trend of molecular weight change, quality loss, and bFGF release was consistent. Meanwhile, microsphere degradation and bFGF release rates in the 4.0 MPa pressure loading group were faster than those in the normal and 0.35 MPa pressure loading groups. It was the fastest in the shaking flask group, showing a statistically significant difference (P<0.0001). In the shearing force loading experiment, there were no distinctive differences in the rates of microsphere degradation and bFGF release between experimental and control group. Meanwhile

  15. Acidic pharmaceuticals in domestic wastewater and receiving water from hyper-urbanization city of China (Shanghai): environmental release and ecological risk.

    PubMed

    Duan, Yan-Ping; Meng, Xiang-Zhou; Wen, Zhi-Hao; Chen, Ling

    2013-01-01

    The occurrence, behavior, and release of five acidic pharmaceuticals, including ibuprofen (IBP), naproxen (NPX), ketoprofen (KEP), diclofenac (DFC), and clofibric acid (CA), have been investigated along the different units in a tertiary-level domestic wastewater treatment plant (WWTP) in hyper-urbanization city of China (Shanghai). IBP was the most abundant chemicals among the measured in raw wastewater. The loads of the acidic pharmaceuticals in the WWTP influent ranged from 7.5 to 414 mg/day/1,000 inh, which were lower than those reported in the developed countries suggesting a less per capita consumption of pharmaceuticals in Shanghai. IBP obtained by highest removal (87 %); NPX and KEP were also significantly removed (69-76 %). However, DFC and CA were only moderately removed by 37-53 %, respectively. Biodegradation seemed to play a key role in the elimination of the studied pharmaceuticals except for DFC and CA. An annual release of acidic pharmaceuticals was estimated at 1,499 and 61.7 kg/year through wastewater and sludge, respectively, from Shanghai. Highest pharmaceuticals concentrations were detected in the effluent discharge point of the WWTP, indicating that WWTP effluent is the main source of the acidic pharmaceuticals to its receiving river. Preliminary results indicated that only DFC in river had a high risk to aquatic organisms. Nevertheless, the joint toxicity effects of these chemicals are needed to further investigate. PMID:22669562

  16. A continuous fluorescence displacement assay for the measurement of phospholipase A2 and other lipases that release long-chain fatty acids.

    PubMed Central

    Wilton, D C

    1990-01-01

    1. A new continuous fluorescence assay for phospholipase A2 is described which involves the displacement of the highly fluorescent fatty-acid probe 11-(dansylamino)undecanoic acid from rat liver fatty-acid-binding protein by long-chain fatty acids released as a result of phospholipase A2-catalysed hydrolysis of phospholipids. The initial rate of decrease in fluorescence is linearly related to enzyme activity. 2. The assay will detect enzyme activity down to about 10 pmol/min per ml and gives a linear response up to about 10 nmol/min per ml. 3. The assay will work with all phospholipids that have been tested including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and phosphatidylglycerol. Substrates carrying a net negative charge showed the highest rates of hydrolysis. 4. The assay will work, in principle, with an enzyme catalysing the release of long-chain fatty acids from a fatty-acylated substrate. This has been confirmed with pancreatic lipase and cholesterol esterase. PMID:2317197

  17. Modulation of spontaneous transmitter release from the frog neuromuscular junction by interacting intracellular Ca(2+) stores: critical role for nicotinic acid-adenine dinucleotide phosphate (NAADP).

    PubMed Central

    Brailoiu, Eugen; Patel, Sandip; Dun, Nae J

    2003-01-01

    Nicotinic acid-adenine dinucleotide phosphate (NAADP) is a recently described potent intracellular Ca(2+)-mobilizing messenger active in a wide range of diverse cell types. In the present study, we have investigated the interaction of NAADP with other Ca(2+)-mobilizing messengers in the release of transmitter at the frog neuromuscular junction. We show, for the first time, that NAADP enhances neurosecretion in response to inositol 1,4,5-trisphosphate (IP(3)), cADP-ribose (cADPR) and sphingosine 1-phosphate (S1P), but not sphingosylphosphorylcholine. Thapsigargin was without effect on transmitter release in response to NAADP, but blocked the responses to subsequent application of IP(3), cADPR and S1P and their potentiation by NAADP. Asynchronous neurotransmitter release may therefore involve functional coupling of endoplasmic reticulum Ca(2+) stores with distinct Ca(2+) stores targeted by NAADP. PMID:12749764

  18. Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

    PubMed Central

    Hsu, Myat Noe; Luo, Rongcong; Kwek, Kerwin Zeming; Por, Yong Chen; Zhang, Yong; Chen, Chia-Hung

    2015-01-01

    The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules. PMID:25825623

  19. Preparation of complex nano-particles based on alginic acid/poly[(2-dimethylamino) ethyl methacrylate] and a drug vehicle for doxorubicin release controlled by ionic strength.

    PubMed

    Cai, Hong; Ni, Caihua; Zhang, Liping

    2012-01-23

    Monodispersed complex nano-particles were synthesized simply by mixing alginic acid (ALG-H) with poly[(2-dimethylamino) ethyl methacrylate] (PDEMA) in pure water without any surfactants or additives. The structure and properties of the nano-particles were extensively studied. The surface charges and average sizes of the nano-particles were varied with the composition of ALG-H and PDEMA. The nano-particles were formed through electrostatic attraction force, and they were very stable in pure water, but dissociated in salt solutions. An anticancer drug (doxorubicin) was loaded in the nano-particles and released in different saline solutions. The release profiles revealed that the drug release could be controlled by adjusting the pH and salt concentrations. The nano-particles displayed apparent advantages such as simple preparation process, low cost, free of organic solvents, size controllable, biodegradable and biocompatible. PMID:22079138

  20. Release and swelling studies of an innovative antidiabetic-bile acid microencapsulated formulation, as a novel targeted therapy for diabetes treatment.

    PubMed

    Mooranian, Armin; Negrulj, Rebecca; Al-Sallami, Hesham S; Fang, Zhongxiang; Mikov, Momir; Golocorbin-Kon, Svetlana; Fakhoury, Marc; Arfuso, Frank; Aruso, Frank; Al-Salami, Hani

    2015-01-01

    In previous studies carried out in our laboratory, a bile acid formulation exerted a hypoglycaemic effect in a rat model of type 1 diabetes (T1D). When the antidiabetic drug gliclazide was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-deoxycholic acid (G-DCA), with good structural properties, excipient compatibility and which exhibited pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH controlled properties of this new formulation. The aim is also to examine the effect of DCA on G release kinetics at various pH values and different temperatures. Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared including: G-SA (control) and G-DCA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, 3, 7.4 and 7.8 and temperatures of 25 °C and 37 °C. The new formulation is further optimised by the addition of DCA. DCA reduced bead-swelling of the microcapsules at pH 7.8 and 3 at 25 °C and 37 °C, and even though bead size remains similar after DCA addition, the percentage of G release was enhanced at high pH values (pH 7.4 and 7.8, p < 0.01). The new formulation exhibits colon-targeted delivery and the addition of DCA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and DCA to the lower intestine. PMID:25265061

  1. Inhibition of HMGB1 release via salvianolic acid B-mediated SIRT1 up-regulation protects rats against non-alcoholic fatty liver disease

    PubMed Central

    Zeng, Wenjing; Shan, Wen; Gao, Lili; Gao, Dongyan; Hu, Yan; Wang, Guangzhi; Zhang, Ning; Li, Zhenlu; Tian, Xiaofeng; Xu, Wei; Peng, Jinyong; Ma, Xiaochi; Yao, Jihong

    2015-01-01

    The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the regulation of HMGB1 in NAFLD, particularly through sirtuin 1 (SIRT1), remains unclear. In this study, we investigated the role of SIRT1-mediated inhibition of HMGB1 release in NAFLD and the effect of salvianolic acid B (SalB), which is a water-soluble phenolic acid extracted from Radix Salvia miltiorrhiza, on NAFLD through SIRT1/HMGB1 signaling. In vivo, SalB treatment significantly attenuated high-fat diet (HFD)-induced liver damage, hepatic steatosis, and inflammation. Importantly, SalB significantly inhibited HMGB1 nuclear translocation and release, accompanied by SIRT1 elevation. In HepG2 cells, palmitic acid (PA)-induced pro-inflammatory cytokines release were blocked by HMGB1 small interfering RNA (siRNA) transfection. Moreover, pharmacological SIRT1 inhibition by Ex527 induced HMGB1 translocation and release, whereas SIRT1 activation by resveratrol or SalB reversed this trend. SIRT1 siRNA abrogated the SalB-mediated inhibition of HMGB1 acetylation and release, suggesting that SalB-mediated protection occurs by SIRT1 targeting HMGB1 for deacetylation. We are the first to demonstrate that the SIRT1/HMGB1 pathway is a key therapeutic target for controlling NAFLD inflammation and that SalB confers protection against HFD- and PA-induced hepatic steatosis and inflammation through SIRT1-mediated HMGB1 deacetylation. PMID:26525891

  2. Differential free fatty acid receptor-1 (FFAR1/GPR40) signalling is associated with gene expression or gelatinase granule release in bovine neutrophils.

    PubMed

    Mena, Sandra J; Manosalva, Carolina; Carretta, Maria D; Teuber, Stefanie; Olmo, Iván; Burgos, Rafael A; Hidalgo, Maria A

    2016-08-01

    Fatty acids have been recognized as regulators of immune function in addition to their known metabolic role. Long-chain fatty acids bind free fatty acid receptor (FFAR)-1/GPR40, which is expressed on bovine neutrophils, and increase responses such as granule release and gene expression. In this study, we investigated the molecular mechanisms governing the up-regulation of cyclooxygenase-2 (COX-2) and IL-8, as well as matrix metalloproteinase (MMP)-9 granule release in FFAR1/GPR40 agonist-stimulated neutrophils. Our results showed that natural (oleic and linoleic acid) and synthetic (GW9508) FFAR1/GPR40 agonists increased ERK1/2, p38 MAPK and Akt phosphorylation, and that the FFAR1/GPR40 antagonist GW1100 reduced these responses. We evaluated the levels of IκBα, a component of the classical activation pathway of the transcription factor NF-κB, and we observed IκBα reduction after stimulation with FFAR1/GPR40 agonists, an effect that was inhibited by GW1100 or the inhibitors UO126, SB203580 or LY294002. FFAR1/GPR40 agonists increased COX-2 and IL-8 expression, which was inhibited by GW1100 and an NF-κB inhibitor. Finally, the FFAR1/GPR40 agonist-induced MMP-9 granule release was reduced by GW1100 and UO126. In conclusion, FFAR1/GPR40 agonists differentially stimulate neutrophil functions; COX-2 and IL-8 are expressed after FFAR1/GPR40 activation via NF-κB, IκBα reduction is FFAR1/GPR40- and PI3K/MAPK-dependent, and MMP-9 granule release is FFAR1/GPR40- and ERK1/2-dependent. PMID:27363707

  3. Ketoprofen-poly(D,L-lactic-co-glycolic acid) microspheres: influence of manufacturing parameters and type of polymer on the release characteristics.

    PubMed

    Gabor, F; Ertl, B; Wirth, M; Mallinger, R

    1999-01-01

    The effect of manufacturing parameters on the size and drug-loading of ketoprofen-containing biodegradable and biocompatible poly(DL-lactic-co-glycolic acid) (PLGA) microspheres prepared by the solvent evaporation method was investigated. For both drug-free and drug-loaded microspheres, smaller microspheres with a narrower size distribution were obtained when the stirring rate or the volume of the organic phase was increased. Incorporation of ketoprofen was found to increase with increasing volume of the organic phase and decreasing pH of the aqueous phase, but was independent of the acidity and the inherent viscosity of the PLGA used. The biphasic release profile of ketoprofen from the microspheres was dependent on the type of PLGA as well as the size and drug-loading, two parameters governed by the manufacturing process. The first burst effect was found to increase with the drug content, reduction of size of the microspheres and increasing inherent viscosity of the matrix, whereas acidity of the PLGA had no effect on the release of this acidic drug. A vigorous first burst effect was associated with reduced sustained delivery of ketoprofen, the rate of the delayed release phase being dependent on the inherent viscosity of the matrix, the size, the payload and the pH during preparation of the microspheres. Thus, by selection of the manufacturing parameters and the type of PLGA, it is possible to design a controlled drug delivery system for the prolonged release of ketoprofen, improving therapy by possible reduction of time intervals between peroral administration and reduction of local gastrointestinal side effects. PMID:9972498

  4. Whey protein/polysaccharide-stabilized emulsions: Effect of polymer type and pH on release and topical delivery of salicylic acid.

    PubMed

    Combrinck, Johann; Otto, Anja; du Plessis, Jeanetta

    2014-06-01

    Emulsions are widely used as topical formulations in the pharmaceutical and cosmetic industries. They are thermodynamically unstable and require emulsifiers for stabilization. Studies have indicated that emulsifiers could affect topical delivery of actives, and this study was therefore designed to investigate the effects of different polymers, applied as emulsifiers, as well as the effects of pH on the release and topical delivery of the active. O/w emulsions were prepared by the layer-by-layer technique, with whey protein forming the first layer around the oil droplets, while either chitosan or carrageenan was subsequently adsorbed to the protein at the interface. Additionally, the emulsions were prepared at three different pH values to introduce different charges to the polymers. The active ingredient, salicylic acid, was incorporated into the oil phase of the emulsions. Physical characterization of the resulting formulations, i.e., droplet size, zeta potential, stability, and turbidity in the water phase, was performed. Release studies were conducted, after which skin absorption studies were performed on the five most stable emulsions, by using Franz type diffusion cells and utilizing human, abdominal skin membranes. It was found that an increase in emulsion droplet charge could negatively affect the release of salicylic acid from these formulations. Contrary, positively charged emulsion droplets were found to enhance dermal and transdermal delivery of salicylic acid from emulsions. It was hypothesized that electrostatic complex formation between the emulsifier and salicylic acid could affect its release, whereas electrostatic interaction between the emulsion droplets and skin could influence dermal/transdermal delivery of the active. PMID:24550100

  5. Swelling, mechanical strength, and release properties of probucol microcapsules with and without a bile acid, and their potential oral delivery in diabetes.

    PubMed

    Negrulj, Rebecca; Mooranian, Armin; Chen-Tan, Nigel; Al-Sallami, Hesham S; Mikov, Momir; Golocorbin-Kon, Svetlana; Fakhoury, Marc; Watts, Gerald F; Arfuso, Frank; Al-Salami, Hani

    2016-08-01

    We have demonstrated a permeation-enhancing effect of deoxycholic acid (DCA), the bile acid, in diabetic rats. In this study, we designed DCA-based microcapsules for the oral delivery of the antilipidemic drug probucol (PB), which has potential antidiabetic effects. We aimed to further characterize these microcapsules and examine their pH-dependent release properties, as well as the effects of DCA on their stability and mechanical strength at various pH and temperature values. Using the polymer sodium alginate (SA), we prepared PB-SA (control) and PB-DCA-SA (test) microcapsules. The microcapsules were examined for drug content, size, surface composition, release, Micro-CT cross-sectional imaging, stability, Zeta potential, mechanical strength, and swelling characteristics at different pH and temperature values. The microencapsulation efficiency and production yield were also examined. The addition of DCA resulted in microcapsules with a greater density and with reduced swelling at a pH of 7.8 and at temperatures of 25°C and 37°C (p < 0.01). The size, surface composition, production yield, and microencapsulation efficiency of the microcapsules remained similar after DCA addition. PB-SA microcapsules produced multiphasic PB release, while PB-DCA-SA microcapsules produced monophasic PB release, suggesting more controlled PB release in the presence of DCA. The PB-DCA-SA microcapsules showed good stability and a pH-sensitive uniphasic release pattern, which may suggest potential applications in the oral delivery of PB in diabetes. PMID:25811999

  6. NMR metabolomics profiling of blood plasma mimics shows that medium- and long-chain fatty acids differently release metabolites from human serum albumin

    NASA Astrophysics Data System (ADS)

    Jupin, M.; Michiels, P. J.; Girard, F. C.; Spraul, M.; Wijmenga, S. S.

    2014-02-01

    Metabolite profiling by NMR of body fluids is increasingly used to successfully differentiate patients from healthy individuals. Metabolites and their concentrations are direct reporters of body biochemistry. However, in blood plasma the NMR-detected free-metabolite concentrations are also strongly affected by interactions with the abundant plasma proteins, which have as of yet not been considered much in metabolic profiling. We previously reported that many of the common NMR-detected metabolites in blood plasma bind to human serum albumin (HSA) and many are released by fatty acids present in fatted HSA. HSA is the most abundant plasma protein and main transporter of endogenous and exogenous metabolites. Here, we show by NMR how the two most common fatty acids (FAs) in blood plasma - the long-chain FA, stearate (C18:0) and medium-chain FA, myristate (C14:0) - affect metabolite-HSA interaction. Of the set of 18 common NMR-detected metabolites, many are released by stearate and/or myristate, lactate appearing the most strongly affected. Myristate, but not stearate, reduces HSA-binding of phenylalanine and pyruvate. Citrate signals were NMR invisible in the presence of HSA. Only at high myristate-HSA mole ratios 11:1, is citrate sufficiently released to be detected. Finally, we find that limited dilution of blood-plasma mimics releases HSA-bound metabolites, a finding confirmed in real blood plasma samples. Based on these findings, we provide recommendations for NMR experiments for quantitative metabolite profiling.

  7. Interactions between protein kinase C and arachidonic acid in the gonadotropin response to salmon and chicken gonadotropin-releasing hormone-II in goldfish.

    PubMed

    Chang, J P; Van Goor, F; Neumann, C M

    1994-03-01

    Previous studies have shown that, in goldfish, the gonadotropin (GTH) response to salmon GTH-releasing hormone (sGnRH) is partly mediated by arachidonic acid (AA) metabolism via the lipoxygenase enzyme system, whereas protein kinase C (PKC) participates in both sGnRH- and chicken (c)GnRH-II-induced GTH secretion. In this study, the interactions between AA- and PKC-dependent pathways in mediating the long-term GnRH stimulation of GTH release were further investigated using dispersed goldfish pituitary cell cultures in static incubation. Treatments with AA or the PKC activator tetradecanoylphorbol acetate (TPA) increased GTH release. The GTH responses to AA and TPA were additive. The lipoxygenase inhibitor nordihydroguairetic acid (NDGA) and the PKC inhibitor H7 selectively reduced AA- and TPA-stimulated GTH release, respectively. These findings suggest that the GTH responses to stimulation by AA- and PKC-dependent signaling pathways are independent of one another. In other experiments, the GTH response to cGnRH-II was unaffected by NDGA but was abolished by H7. In contrast, sGnRH-induced GTH release was attenuated by NDGA and H7. Furthermore, in the presence of both NDGA and H7, the GTH response to sGnRH was abolished. These data suggest that sGnRH stimulation of GTH secretion involves both AA- and PKC-dependent mechanisms; in contrast, cGnRH-II action is not dependent on AA metabolism. The pathway by which AA might be mobilized in response to a GnRH challenge was also investigated by pharmacological manipulations. The diacylglcerol (DG) lipase inhibitor, U-57908, did not decrease sGnRH- and cGnRH-II-induced GTH secretion. On the other hand, the phospholipase A2 (PLA2) inhibitors, bromophenacyl bromide (BPB), chloroquine, and quinacrine, reduced sGnRH-elicited, but not cGnRH-II-stimulated GTH release. The addition of AA reversed the inhibitory action of BPB on sGnRH-elicited GTH release. In addition, the GTH response to AA was additive to the cGnRH-II-induced, but

  8. Chemical design of pH-sensitive nanovalves on the outer surface of mesoporous silicas for controlled storage and release of aromatic amino acid

    SciTech Connect

    Roik, N.V. Belyakova, L.A.

    2014-07-01

    Mesoporous silicas with hexagonally arranged pore channels were synthesized in water–ethanol-ammonia solution using cetyltrimethylammonium bromide as template. Directed modification of silica surface with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups was realized by postsynthetic activation of halogenoalkylsilicas, which have surface uniformly or selectively distributed 3-chloropropyl groups, with 2-aminodiphenylamine in the liquid phase. Chemical composition of silica materials was estimated by IR spectroscopy and chemical analysis of the surface products of reactions. Characteristics of porous structure of MCM-41-type silicas were determined from X-ray and low-temperature nitrogen ad-desorption measurements. Release ability of synthesized silica carriers was established on encapsulation of 4-aminobenzoic acid in pore channels and subsequent delivery at pH=6.86 and pH=1.00. It was found that N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups block pore entrances at neutral pH preventing 4-aminobenzoic acid release. At pH=1.00 repulsion of positively charged surface aromatic amino groups localized near pore orifices provides unhindered liberation of aromatic amino acid from mesoporous channels. - Graphical abstract: Blocking of pores with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups at pH=6.86 for storage of ABA and opening of pore entrances at pH=1.00 for unhindered ABA liberation. - Highlights: • Modification of MCM-41 with N-[N′-(N′-phenyl)-2-aminophenyl]-3-aminopropyl groups. • Study of release ability of synthesized silica carriers in relation to amino acid. • Controlled blocking and opening of pores by amino groups at pH change were performed. • Retention of amino acid at pH=6.86 and its liberation at pH=1.00 was proved.

  9. Effect of desferrioxamine B and Suwannee River fulvic acid on Fe(III) release and Cr(III) desorption from goethite

    NASA Astrophysics Data System (ADS)

    Stewart, Angela G.; Hudson-Edwards, Karen A.; Dubbin, William E.

    2016-04-01

    Siderophores are biogenic chelating ligands that facilitate the solubilisation of Fe(III) and form stable complexes with a range of contaminant metals and therefore may significantly affect their biogeochemical cycling. Desferrioxamine B (DFOB) is a trihydroxamate siderophore that acts synergistically with fulvic acid and low molecular weight organic ligands to release Fe from Fe(III) oxides. We report the results of batch dissolution experiments in which we determine the rates of Cr(III) desorption and Fe(III) release from Cr(III)-treated synthetic goethite as influenced by DFOB, by fulvic acid, and by the two compounds in combination. We observed that adsorbed Cr(III) at 3% surface coverage significantly reduced Fe(III) release from goethite for all combinations of DFOB and fulvic acid. When DFOB (270 μM) was the only ligand present, dissolved Fe(III) and Cr(III) increased approximately 1000-fold and 16-fold, respectively, as compared to the ligand-free system, a difference we attribute to the slow rate of water exchange of Cr(III). Suwannee River fulvic acid (SRFA) acts synergistically with DFOB by (i) reducing the goethite surface charge leading to increased HDFOB+ surface excess and by (ii) forming aqueous Fe(III)-SRFA species whose Fe(III) is subsequently removed by DFOB to yield aqueous Fe(III)-DFOB complexes. These observations shed new light on the synergistic relationship between DFOB and fulvic acid and reveal the mechanisms of Fe(III) acquisition available to plants and micro-organisms in Cr(III) contaminated environments.

  10. Characterizing the release of different composition of dissolved organic matter in soil under acid rain leaching using three-dimensional excitation-emission matrix spectroscopy.

    PubMed

    Liu, Li; Song, Cunyi; Yan, Zengguang; Li, Fasheng

    2009-09-01

    Although excitation-emission matrix spectroscopy (EEMS) has been widely used to characterize dissolved organic matter (DOM), there has no report that EEMS has been used to study the effects of acid rain on DOM and its composition in soil. In this work, we employed three-dimensional EEMS to characterize the compositions of DOM leached by simulated acid rain from red soil. The red soil was subjected to leaching of simulated acid rain of different acidity, and the leached DOM presented five main peaks in its EEMS: peak-A, related to humic acid-like (HA-like) material, at Ex/Em of 310-330/395-420nm; peak-B, related to UV fulvic acid-like (FA-like) material, at Ex/Em of 230-280/400-435nm; peak-C and peak-D, both related to microbial byproduct-like material, at Ex/Em of 250-280/335-355nm and 260-280/290-320nm, respectively; and peak-E, related to simple aromatic proteins, at Ex/Em of 210-240/290-340nm. EEMS analysis results indicated that most DOM could be lost from red soil in the early phase of acid rain leaching. In addition to the effects of the pH of acid rain, the loss of DOM also depended on the properties of its compositions and the solubility of their complexes with aluminum. HA-like and microbial byproduct-like materials could be more easily released from red soil by acid rain at both higher pH (4.5 and 5.6) and lower pH (2.5 and 3) than that at middle pH (3.5). On the contrary, FA-like material lost in a similar manner under the action of different acid rains with pH ranging from 2.5 to 5.6. PMID:19577791

  11. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    SciTech Connect

    Shrestha, Chandan; Ito, Takashi; Kawahara, Ko-ichi; Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto; Maruyama, Ikuro

    2013-08-09

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

  12. Controlled Release of Linalool Using Nanofibrous Membranes of Poly(lactic acid) Obtained by Electrospinning and Solution Blow Spinning: A Comparative Study.

    PubMed

    Souza, Michelle A; Oliveira, Juliano E; Medeiros, Eliton S; Glenn, Gregory M; Mattoso, Luiz H C

    2015-08-01

    The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofibrous membranes produced by electrospinning and solution blow spinning (SBS) as well as the effect of linalool on fiber morphology and structural properties. PLA nanofibrous membranes were characterized by Scanning Electron Microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and contact angle measurements. The average diameters of the electrospun and solution blow spun nanofibers were similar, ranging from 176 to 240 nm. Linalool behaved as a plasticizer to PLA decreasing the glass transition temperature (Tg), melting point (Tm) and crystallization temperature (TC) of PLA. Curves of the release of linalool at 35 °C were non-linear, showing a clear biphasic pattern consistent with one or more Fickian release components. The time required to release 50% of linalool (t1/2) decreased with increasing linalool concentration. The range in t1/2 values for SBS nanofibers was higher (291-1645s) than the t1/2 values for electrospun fibers (76-575s). PMID:26369129

  13. The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles.

    PubMed

    Al-Qadi, Sonia; Alatorre-Meda, Manuel; Martin-Pastor, Manuel; Taboada, Pablo; Remuñán-López, Carmen

    2016-05-01

    The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. Such analysis allowed us to elucidate the type and extent of interactions established by INS within the hybrid nanoparticles and to get further knowledge on the nature of its release mechanism in vitro. Overall, INS release from the CS nanoparticles was thermodynamically driven, and when including HA a weaker INS binding to the nanoparticles, hence, a faster release rate in vitro were observed. As a negative polyelectrolyte, HA might have sterically blocked the activated sites of CS, such as the amino groups, through chain entanglement, thereby, attenuating the competitive binding interactions of INS. As a consequence, INS might have experienced a spatial exclusion onto the surface of the hybrid nanoparticles to a greater extent which, in turn, would explain its initial abrupt release. PMID:26854581

  14. Early release of arachidonic acid prevents an otherwise immediate formation of toxic levels of peroxynitrite in astrocytes stimulated with lipopolysaccharide/interferon-gamma.

    PubMed

    Palomba, Letizia; Amadori, Alessandra; Cantoni, Orazio

    2007-11-01

    Addition of bacterial lipopolysaccharides (LPS) and interferon-gamma (IFN-gamma) to rat astrocytes in primary culture promotes an early release of arachidonic acid (ARA) associated with an immediate inhibition of neuronal nitric oxide synthase (nNOS). Preventing the release of constitutive nitric oxide (NO) is indeed critical for activation of the nuclear factor kappa B, and for the expression of inducible nitric oxide synthase responsible for the formation of large amounts of NO. LPS/IFN-gamma also promotes an early release of superoxide, via activation of NADPH oxidase, but the generation of peroxynitrite (ONOO-) is prevented by the different timing of superoxide (minutes) and NO (hours) formation. Upstream inhibition of the ARA-dependent nNOS inhibitory signaling, however, caused the parallel release of superoxide and constitutive NO, thereby leading to formation of ONOO- levels triggering loss of ATP and mitochondrial membrane potential followed by the mitochondrial release of cytochrome c, activation of caspase 3 and morphological evidence of apoptosis. Nanomolar levels of exogenous ARA prevented all these events via inhibition of early ONOO- formation. Thus, the ARA-dependent nNOS inhibition observed in astrocytes exposed to pro-inflammatory stimuli, as LPS/IFN-gamma, is critical for both the expression of nuclear factor kappa B-dependent genes and for survival. PMID:17666049

  15. Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent

    PubMed Central

    Nilsson, Christer L; Hellstrand, Monika; Ekman, Agneta; Eriksson, Elias

    1998-01-01

    In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (−)-(3-hydroxyphenyl)-N-n-propylpiperidine [(−)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (−)-sulpiride–but not by (+)-sulpiride–and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines. PMID:9756380

  16. Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases

    PubMed Central

    Harrigan, Timothy J.; Abdullaev, Iskandar F.; Jourd'heuil, David; Mongin, Alexander A.

    2008-01-01

    Microglia are the resident immune cells of the CNS, which are important for preserving neural tissue functions, but may also contribute to neurodegeneration. Activation of these cells in infection, inflammation, or trauma leads to the release of various toxic molecules, including reactive oxygen species (ROS) and the excitatory amino acid glutamate. In this study we used an electrophysiological approach and a D-[3H]aspartate (glutamate) release assay to explore the ROS-dependent regulation of glutamate-permeable volume-regulated anion channels (VRACs). Exposure of rat microglia to hypoosmotic media stimulated Cl− currents and D-[3H]aspartate release, both of which were inhibited by the selective VRAC blocker DCPIB. Exogenously applied H2O2 potently increased swelling-activated glutamate release. Stimulation of microglia with zymosan triggered production of endogenous ROS and strongly enhanced glutamate release via VRAC in swollen cells. The effects of zymosan were attenuated by the ROS scavenger MnTMPyP, and by two inhibitors of NADPH oxidase (NOX) diphenyliodonium and thioridazine. However, zymosan-stimulated glutamate release was insensitive to other NOX blockers, apocynin and AEBSF. This pharmacological profile pointed to the potential involvement of apocynin-insensitive NOX4. Using RT-PCR we confirmed that NOX4 is expressed in rat microglial cells, along with NOX1 and NOX2. To check for potential involvement of phagocytic NOX2 we stimulated this isoform using protein kinase C (PKC) activator PMA, or inhibited it with the broad spectrum PKC blocker Gö6983. Both agents potently modulated endogenous ROS production by NOX2, but not VRAC activity. Taken together, these data suggest that the anion channel VRAC may contribute to microglial glutamate release, and that its activity is regulated by endogenous ROS originating from NOX4. PMID:18624925

  17. A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R.; Khan, Haseeb A.; Cho, Kwang Jae; Lee, Yong-Kyu

    2015-06-01

    The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid

  18. Differential effects of polybrominated diphenyl ethers and polychlorinated biphenyls on [3H]arachidonic acid release in rat cerebellar granule neurons.

    PubMed

    Kodavanti, Prasada Rao S; Derr-Yellin, Ethel C

    2002-08-01

    Polybrominated diphenyl ethers (PBDEs), which are widely used as flame-retardants, have been increasing in environmental and human tissue samples during the past 20-30 years, while other structurally related, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (on a TEQ basis), have decreased. PBDEs have been detected in human blood, adipose tissue, and breast milk, and developmental and long-term exposure to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that PCBs, which cause neurotoxic effects, including changes in learning and memory, stimulated the release of [(3)H]arachidonic acid ([(3)H]AA) by a cPLA(2)/iPLA(2)-dependent mechanism. PLA(2)(phospholipase A(2)) activity has been associated with learning and memory, and AA has been identified as a second messenger involved in synaptic plasticity. The objective of the present study was to test whether PBDE mixtures (DE-71 and DE-79), like other organohalogen mixtures, have a similar action on [(3)H]AA release in an in vitro neuronal culture model. Cerebellar granule cells at 7 days in culture were labeled with [(3)H]AA for 16-20 h and then exposed in vitro to PBDEs. DE-71, a mostly pentabromodiphenyl ether mixture, significantly stimulated [(3)H]AA release at concentrations as low as 10 microg/ml, while DE-79, a mostly octabromodiphenyl ether mixture, did not stimulate [(3)H]AA release, even at 50 microg/ml. The release of [(3)H]AA by DE-71 is time-dependent, and a significant increase was seen after only 5-10 min of exposure. The removal and chelation of calcium from the exposure buffer, using 0.3 mM EGTA, significantly attenuated the DE-71-stimulated [(3)H]AA release; however, only an 18% inhibition of the release was demonstrated for the calcium replete conditions at 30 microg/ml DE-71. Methyl arachidonylfluorophosphonate (5 microM), an inhibitor of cPLA(2)/iPLA(2), completely attenuated the DE-71

  19. Host-pathogen interactions. XXIX. Oligogalacturonides released from sodium polypectate by endopolygalacturonic acid lyase are elicitors of phytoalexins in soybean. [Glycine max L

    SciTech Connect

    Davis, K.R.; Darvill, A.G.; Albersheim, P.; Dell, A.

    1986-02-01

    Recent studies have demonstrated that an apparently homogeneous preparation of an ..cap alpha..-1,4-D-endopolygalacturonic acid lyase (EC 4.2,2.2) isolated from the phytopathogenic bacterium Erwinia carotovora induced phytoalexin accumulation in cotyledons of soybean (Glycine max (L.) Merr. cv Wayne) and that this pectin-degrading enzyme released heat-stable elicitors of phytoalexins from soybean cell walls, citrus pectin, and sodium polypectate. The present paper reports the purification, by anion-exchange chromatography on QAE-Sephadex columns followed by gel-permeation chromatography on a Bio-Gel P-6 column, of the two fractions with highest specific elicitor activity present in a crude elicitor-preparation obtained by lyase treatment of sodium polypectate. Structural analysis of the fraction with highest specific elicitor activity indicated that the major, if not only, component was a decasaccharide of ..cap alpha..-1,4-D-galactosyluronic acid that contained the expected product of lyase cleavage, 4-deoxy-..beta..-L-5-threo-hexopyranos-4-enyluronic acid (4,5-unsaturated galactosyluronic acid), at the nonreducing terminus. This modified decagalacturonide fraction exhibited half-maximum and maximum elicitor activity at 1 microgram/cotyledon (6 micromolar) and 5 micrograms/cotyledon (32 micromolar) galactosyluronic acid equivalents, respectively. Reducing 90 to 95% of the carboxyl groups of the galactosyluronic acid residues abolished the elicitor activity of the decagalacturonide fraction. The second most elicitor-active fraction contained mostly undeca-..cap alpha..-1,4-D-galactosyluronic acid that contained 4,5-unsaturated galactosyluronic acid at the nonreducing termini. This fraction exhibited half-maximum and maximum elicitor activity at approximately 3 micrograms/cotyledon (17 micromolar) and 6 micrograms/cotyledon (34 micromolar) galactosyluronic acid equivalents, respectively.

  20. Cluster of Differentiation 38 (CD38) Mediates Bile Acid-induced Acinar Cell Injury and Pancreatitis through Cyclic ADP-ribose and Intracellular Calcium Release*

    PubMed Central

    Orabi, Abrahim I.; Muili, Kamaldeen A.; Javed, Tanveer A.; Jin, Shunqian; Jayaraman, Thottala; Lund, Frances E.; Husain, Sohail Z.

    2013-01-01

    Aberrant Ca2+ signals within pancreatic acinar cells are an early and critical feature in acute pancreatitis, yet it is unclear how these signals are generated. An important mediator of the aberrant Ca2+ signals due to bile acid exposure is the intracellular Ca2+ channel ryanodine receptor. One putative activator of the ryanodine receptor is the nucleotide second messenger cyclic ADP-ribose (cADPR), which is generated by an ectoenzyme ADP-ribosyl cyclase, CD38. In this study, we examined the role of CD38 and cADPR in acinar cell Ca2+ signals and acinar injury due to bile acids using pharmacologic inhibitors of CD38 and cADPR as well as mice deficient in Cd38 (Cd38−/−). Cytosolic Ca2+ signals were imaged using live time-lapse confocal microscopy in freshly isolated mouse acinar cells during perifusion with the bile acid taurolithocholic acid 3-sulfate (TLCS; 500 μm). To focus on intracellular Ca2+ release and to specifically exclude Ca2+ influx, cells were perifused in Ca2+-free medium. Cell injury was assessed by lactate dehydrogenase leakage and propidium iodide uptake. Pretreatment with either nicotinamide (20 mm) or the cADPR antagonist 8-Br-cADPR (30 μm) abrogated TLCS-induced Ca2+ signals and cell injury. TLCS-induced Ca2+ release and cell injury were reduced by 30 and 95%, respectively, in Cd38-deficient acinar cells compared with wild-type cells (p < 0.05). Cd38-deficient mice were protected against a model of bile acid infusion pancreatitis. In summary, these data indicate that CD38-cADPR mediates bile acid-induced pancreatitis and acinar cell injury through aberrant intracellular Ca2+ signaling. PMID:23940051

  1. Acid-Triggered Release via dePEGylation of Fusogenic Liposomes Mediated by Heterobifunctional Phenyl Substituted Vinyl Ethers with Tunable pH-Sensitivity

    PubMed Central

    Kim, Hee-Kwon; Van den Bossche, Jeroen; Hyun, Seok-Hee; Thompson, David H

    2012-01-01

    A new family of heterobifunctional phenyl-substituted vinyl ether (PIVE) coupling agents with tunable acid-sensitivity has been developed. The PIVE compounds are designed to hydrolyze under acidic conditions with hydrolysis rates that can be varied by rational selection of the phenyl ring substituent. These reagents were incorporated within 2-methoxypoly(ethylene glycol) PEG-conjugated 1,3-dioctadecyl-rac-glycerol lipids to produce the acid-cleavable lipopolymers mPEG-[H-PIVE]-DOG, mPEG-[F-PIVE]-DOG, mPEG-[Me-PIVE]-DOG, and mPEG-[MeO-PIVE]-DOG. These lipopolymers were hydrolyzed under acidic conditions (pH 3.5 or 4.5) at rates that were dependent on the electron donating or withdrawing character of the α-phenyl vinyl ether substituent, while remaining stable at pH 7.4. Blending of these compounds with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in a 10:90 mPEG-PIVE-Lipid:DOPE ratio produced stable liposomes at neutral pH; however, acidification of the solution led to dePEGylation and release of the liposomal cargo in a manner that correlated with the PIVE proton affinity. Specifically, we observed 70 % calcein release within 12 h from mPEG-[MeO-PIVE]-DOG-containing liposomes at pH 4.5, whereas only 22% calcein release was observed from mPEG-[F-PIVE]-DOG:DOPE liposomes over this same timescale and pH. These results indicate that dePEGylation following acidification is a triggering mechanism that can be rationally designed and controlled through the appropriate selection of PIVE moieties. PMID:22988941

  2. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    PubMed Central

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction. PMID:19166917

  3. Evaluation of ursodeoxycholic acid bioavailability from immediate- and sustained-release preparations using gas chromatography-mass spectrometry and high-performance liquid chromatography.

    PubMed

    Scalia, S; Scagliarini, R; Pazzi, P

    2000-02-01

    An improved procedure is presented for the determination of ursodeoxycholic acid (CAS 128-13-2, UDCA) in human plasma and bile after oral administration of UDCA-containing dosage forms. The plasma samples after solid-phase extraction with silica-based C18- and strong anion exchange cartridges were assayed by gas chromatography-mass spectrometry (GC-MS) using selected-ion monitoring. The hexafluoroisopropyl trifluoroacetate ester derivative of UDCA was selected for GC analysis since it is easily and rapidly prepared by a one-step reaction. Biliary UDCA levels were determined by a rapid and simple high-performance liquid chromatographic (HPLC) method with on-line sample purification. This analytical protocol was used to investigate the pharmacokinetic of a new sustained-release capsule of UDCA in comparison with a reference immediate-release preparation after single oral administration. Statistical evaluation of the area under the plasma concentration-time curves indicated that two formulations are equivalent with regard to the amount of drug absorbed. However, pharmacokinetic data showed that with the sustained-release preparation a significantly delayed mean peak plasma level was reached compared with the reference preparation. Moreover, the immediate- and extended-release capsules were found to achieve a comparable degree of biliary enrichment with UDCA. PMID:10719615

  4. Evaluation of Controlled-Release Property and Phytotoxicity Effect of Insect Pheromone Zinc-Layered Hydroxide Nanohybrid Intercalated with Hexenoic Acid.

    PubMed

    Ahmad, Rozita; Hussein, Mohd Zobir; Kadir, Wan Rasidah Wan Abdul; Sarijo, Siti Halimah; Hin, Taufiq-Yap Yun

    2015-12-30

    A controlled release formulation for the insect pheromone hexenoic acid (HE) was successfully developed using zinc-layered hydroxide (ZLH) as host material through a simple coprecipitation technique, resulting in the formation of inorganic-organic nanolayered material with sustained release properties. The release of HE from its nanohybrid was found to occur in a controlled manner, governed by a pseudo-second order kinetics model. The maximum amount of HE released from the nanocomposite into solutions at pH 4, 6.5, and 8 was found to be 84, 73, and 83% for 1100 min, respectively. The hexenoate zinc-layered hydroxide nanomaterial (HEN) was found to be nontoxic for plants when green beans and wheat seeds were successfully germinated in all HEN concentrations tested in the experiment, with higher percentage of seed germination and higher radical seed growth as compared to its counter anion, HE. ZLH can be a promising carrier for insect pheromone toward a new generation of environmentally safe pesticide nanomaterial for crop protection. PMID:26501358

  5. Topical application of a film-forming emulgel dressing that controls the release of stratifin and acetylsalicylic acid and improves/prevents hypertrophic scarring.

    PubMed

    Rahmani-Neishaboor, Elham; Jallili, Reza; Hartwell, Ryan; Leung, Victor; Carr, Nicholas; Ghahary, Aziz

    2013-01-01

    Here, we evaluate the efficacy of an emulgel dressing to control the release of an antifibrogenic factor, stratifin (SFN), along with an anti-inflammatory drug, acetylsalicylic acid (ASA), to be used as a wound dressing with hypertrophic scar reducing features. Emulgel dressings were prepared by dispersing positively charged submicron vesicles in carboxymethyl cellulose gel. Release kinetics of SFN/ASA and toxicity for primary skin cells were assessed in vitro. Antifibrogenic efficacy of medicated emulgel dressings was tested on a rabbit ear fibrotic model. Following topical application on the wounds, emulgels formed an occlusive film and controlled the release of SFN and ASA for 7 and 24 hours, respectively. Wounds treated with SFN/ASA-containing emulgel dressings showed an 80% reduction in scar elevation compared with untreated controls. Topical formulations were nontoxic for cultured human keratinocytes and fibroblasts. Inflammation was significantly controlled in treated wounds, as shown by a reduced number of infiltrated CD3(+) T cells (p < 0.001) and macrophages. SFN/ASA-treated wounds showed a significantly higher (p < 0.001) expression of matrix metalloproteinase-1, resulting in reduced collagen deposition and less scarring. Film-forming emulgel dressings that control the release of antifibrogenic and anti-inflammatory factors provide an excellent treatment option for postburn hypertrophic scar management. PMID:23126516

  6. pH-responsive controlled-release fertilizer with water retention via atom transfer radical polymerization of acrylic acid on mussel-inspired initiator.

    PubMed

    Ma, Zhi-yuan; Jia, Xin; Zhang, Guo-xiang; Hu, Jia-mei; Zhang, Xiu-lan; Liu, Zhi-yong; Wang, He-yun; Zhou, Feng

    2013-06-12

    This work reports a polydopamine-graft-poly(acrylic acid) (Pdop-g-PAA)-coated controlled-release multi-element compound fertilizer with water-retention function by a combination of mussel-inspired chemistry and surface-initiated atom transfer radical polymerization (SI-ATRP) techniques for the first time. The morphology and composition of the products were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), gel permeation chromatography (GPC), and inductively coupled plasma (ICP) emission spectrometry. The results revealed that the stimuli-responsive layer formed by a Pdop inner layer and a PAA outer corona exhibit outstanding selective permeability to charged nutrients and the release rate of encapsulated elements can be tailored by the pH values. At low pH, the Pdop-g-PAA layer can reduce nutrient loss, and at high pH, the coating restrains transportation of negative nutrients but favors the release of cations. Moreover, PAA brushes provide good water-retention property. This Pdop-graft-polymer brushes coating will be effective and promising in the research and development of multi-functional controlled-release fertilizer. PMID:23692274

  7. Chemical design of pH-sensitive nanovalves on the outer surface of mesoporous silicas for controlled storage and release of aromatic amino acid

    NASA Astrophysics Data System (ADS)

    Roik, N. V.; Belyakova, L. A.

    2014-07-01

    Mesoporous silicas with hexagonally arranged pore channels were synthesized in water-ethanol-ammonia solution using cetyltrimethylammonium bromide as template. Directed modification of silica surface with N-[N‧-(N‧-phenyl)-2-aminophenyl]-3-aminopropyl groups was realized by postsynthetic activation of halogenoalkylsilicas, which have surface uniformly or selectively distributed 3-chloropropyl groups, with 2-aminodiphenylamine in the liquid phase. Chemical composition of silica materials was estimated by IR spectroscopy and chemical analysis of the surface products of reactions. Characteristics of porous structure of MCM-41-type silicas were determined from X-ray and low-temperature nitrogen ad-desorption measurements. Release ability of synthesized silica carriers was established on encapsulation of 4-aminobenzoic acid in pore channels and subsequent delivery at pH=6.86 and pH=1.00. It was found that N-[N‧-(N‧-phenyl)-2-aminophenyl]-3-aminopropyl groups block pore entrances at neutral pH preventing 4-aminobenzoic acid release. At pH=1.00 repulsion of positively charged surface aromatic amino groups localized near pore orifices provides unhindered liberation of aromatic amino acid from mesoporous channels.

  8. Production of a chimeric enzyme tool associating the Trichoderma reesei swollenin with the Aspergillus niger feruloyl esterase A for release of ferulic acid.

    PubMed

    Levasseur, Anthony; Saloheimo, Markku; Navarro, David; Andberg, Martina; Monot, Frédéric; Nakari-Setälä, Tiina; Asther, Marcel; Record, Eric

    2006-12-01

    The main goals of this work were to produce the fusion protein of the Trichoderma reesei swollenin I (SWOI) and Aspergillus niger feruloyl esterase A (FAEA) and to study the effect of the physical association of the fusion partners on the efficiency of the enzyme. The fusion protein was produced up to 25 mg l(-1) in the T. reesei strains Rut-C30 and CL847. In parallel, FAEA alone was produced for use as a control protein in application tests. Recombinant FAEA and SWOI-FAEA were purified to homogeneity and characterized. The biochemical and kinetic characteristics of the two recombinant proteins were found to be similar to those of native FAEA, except for the temperature stability and specific activity of the SWOI-FAEA. Finally, the SWOI-FAEA protein was tested for release of ferulic acid from wheat bran. A period of 24 h of enzymatic hydrolysis with the SWOI-FAEA improved the efficiency of ferulic acid release by 50% compared with the results obtained using the free FAEA and SWOI. Ferulic acid is used as an antioxidant and flavor precursor in the food and pharmaceutical industries. This is the first report of a potential application of the SWOI protein fused with an enzyme of industrial interest. PMID:16957894

  9. The release of N-acetyl- and N-glycolloyl-neuraminic acid from soluble complex carbohydrates and erythrocytes by bacterial, viral and mammalian sialidases.

    PubMed Central

    Corfield, A P; Veh, R W; Wember, M; Michalski, J C; Schauer, R

    1981-01-01

    A series of substrates, sialyl(2 leads to 6)GalNAc and ganglioside GM3, containing either N-acetylneuraminic acid (AcNeu) or N-glycolloylneuraminic acid (GcNeu), has been prepared. The trisaccharide GcNeu(2 leads to 3)lactose was preapred by ozonolysis of GcNeu-GM3, and the disaccharides AcNeu(2 leads to 6)GalNAc and GcNeu(2 leads to 6)GalNAc were isolated from bovine submandibular-gland mucin by alkali elimination. Sialidases from Newcastle-disease virus, fowl-plague virus, influenza virus A2, Clostridium perfringens, Vibrio cholerae, Arthrobacter ureafaciens and human liver lysosomes were studied with the above substrates and all showed poorer cleavage of GcNeu-containing substrates when compared with the corresponding AcNeu-containing compounds. This was reflected in the Km and Vmax. values of these sialidases. Differences between viral and bacterial sialidases could be detected on the basis of their kinetic constants and time curves of sialic acid release. Preferred release of AcNeu relative to GcNeu was also observed with bovine submandibular gland mucin and a mixture of human and porcine erythrocytes, macromolecular substrates containing both AcNeu and GcNeu. The significance of differential cleavage of AcNeu and GcNeu by sialidases is considered together with examples of the role of GcNeu in physiologicaL systems. PMID:7325957

  10. The stability and controlled release of I-ascorbic acid encapsulated in poly (ethyl-2-cyanoacrylate) nanocapsules prepared by interfacial polymerization of water-in-oil microemulsions.

    PubMed

    Zhang, Su-Ning; Chen, Tao; Guo, Yi-Guang; Zhang, Jian; Song, Xiaoqiu; Zhou, Lei

    2015-01-01

    The L-ascorbic acid (AA) was encapsulated into biodegradable and biocompatible poly(ethyl-2-cyanoacrylate) (PECA) nanocapsules by interfacial polymerization of water-in-oil (W/O) microemulsions. The influences of surfactant concentration, pH value of the dispersed aqueous phase, and W/O ratio on nanocapsule size were discussed. The stability and in vitro release of encapsulated AA were also investigated. The results show that nanocapsules could be obtained under the conditions with low pH value, high fraction of aqueous phase, and appropriate surfactant concentration. The encapsulated AA was protected by nanocapsules from oxidation and presented superior storage stability in aqueous medium than pure AA. Releasing AA from the inner core of nanocapsules could be controlled by adjusting the enzyme hydrolysis extent of the PECA wall. PMID:26665980

  11. Intercalation and controlled release of 2,4-dichlorophenoxyacetic acid using rhombohedral [LiAl2(OH)6]Cl·xH2O

    NASA Astrophysics Data System (ADS)

    Ragavan, Anusha; Khan, Aamir I.; O'Hare, Dermot

    2006-05-01

    2,4-Dichlorophenoxyacetic acid (2,4-D) has been fully intercalated into the rhombohedral polymorph of [LiAl2(OH)6]Cl·xH2O ([rhom-Li Al] LDH) by an ion exchange method. The controlled release of 2,4-D from the interlamellar spaces of [rhom-Li Al] LDH has been studied in a phosphate buffer, natural rainwater and deionised water. In buffer solution and rainwater, the intercalated herbicide is exchanged for anions in solution. In contrast, in deionised water the herbicide is released as part of the Li+/herbicide ion pair, leading to the formation of Al(OH)3 and the solvated ions.

  12. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    PubMed

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa

    2015-08-01

    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (<2800 μA), TFS enhances and decreases the basal extracellular levels of GABA and glutamate, respectively. However, TFS did not modify the ADT. During the second microdialysis experiment, a group of animals was subjected to SE induced by pilocarpine administration (300 mg/kg, i.p.; SE group). The SE was associated with a significant rise of GABA and glutamate release (up to 120 and 182% respectively, 5h after pilocarpine injection) and the prevalence of high-voltage rhythmic spikes and increased spectral potency of delta, gamma, and theta bands. A group of animals (SE-TFS group) received TFS continuously during 2h at 100 μA, 5 min after the establishment of SE. This group showed a significant decrease in the expression of the convulsive activity and spectral potency in gamma and theta bands. The extracellular levels of GABA and glutamate in the hippocampus remained at basal conditions. These results suggest that TFS induces anticonvulsant effects when applied during the SE, an effect associated with lower amino acid release. This article is part of a Special Issue entitled "Status Epilepticus". PMID:26006058

  13. Aspartic acid

    MedlinePlus

    ... also called asparaginic acid. Aspartic acid helps every cell in the body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as ...

  14. Release of Propolis Phenolic Acids from Semisolid Formulations and Their Penetration into the Human Skin In Vitro

    PubMed Central

    Ramanauskienė, Kristina; Briedis, Vitalis

    2013-01-01

    Antioxidant and free radical scavenging effects are attributed to phenolic compounds present in propolis, and when delivered to the skin surface and following penetration into epidermis and dermis, they can contribute to skin protection from damaging action of free radicals that are formed under UV and premature skin aging. This study was designed to determine the penetration of phenolic acids and vanillin into the human skin in vitro from experimentally designed vehicles. Results of the study demonstrated the ability of propolis phenolic acids (vanillic, coumaric, caffeic, and ferulic acids) and vanillin to penetrate into skin epidermis and dermis. The rate of penetration and distribution is affected both by physicochemical characteristics of active substances and physical structure and chemical composition of semisolid vehicle. Vanillin and vanillic acid demonstrated relatively high penetration through epidermis into dermis where these compounds were concentrated, coumaric and ferulic acids were uniformly distributed between epidermis and dermis, and caffeic acid slowly penetrated into epidermis and was not determined in dermis. Further studies are deemed relevant for the development of semisolid topically applied systems designed for efficient delivery of propolis antioxidants into the skin. PMID:23762175

  15. Polymeric nanoparticles loaded with the 3,5,3′-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics

    PubMed Central

    dos Santos, Karen C; da Silva, Maria Fatima GF; Pereira-Filho, Edenir R; Fernandes, Joao B; Polikarpov, Igor; Forim, Moacir R

    2012-01-01

    This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3′-triiodothyroacetic acid (Triac). A 211–6 fractional factorial design and another 22 factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment. PMID:24198495

  16. Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent.

    PubMed

    Siafaka, Panoraia I; Barmbalexis, Panagiotis; Bikiaris, Dimitrios N

    2016-06-10

    In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR. PMID:27039136

  17. Development of a novel controlled-release nanocomposite based on poly(lactic acid) to increase the oxidative stability of soybean oil.

    PubMed

    Almasi, Hadi; Ghanbarzadeh, Babak; Dehghannya, Jalal; Entezami, Ali Akbar; Khosrowshahi Asl, Asghar

    2014-01-01

    A poly(lactic acid) (PLA)-based nanocomposite active packaging was developed for the controlled release of tert-butylhydroquinone (TBHQ) antioxidant. The PLA-based active films were loaded with only TBHQ (3% wt) or a mixture of modified cellulose nanofibre (MCNF) (8% wt) and TBHQ (3% wt) to obtain active and nanocomposite active films, respectively. Release studies indicated that the release rate of TBHQ in 95% ethanol simulant was significantly decreased by the addition of MCNF. Moreover, the presence of MCNF diminished the increasing effect of temperature on the release rate as when storage temperature increased from 4°C to 40°C. The diffusion coefficient (D) for PLA-TBHQ and PLA-MCNF-TBHQ films increased from 6.75 and 4.34 × 10(-8) cm(2) s(-1) to 19.85 and 8.49 × 10(-8) cm(2) s(-1), respectively. Diffusion of TBHQ to soybean oil was enough to delay the induction of the oxidation of soybean oil stored for 6 months in contact with PLA-based films. Antioxidative activity of PLA-based active films considerably increased with increasing storage time as indicated by the increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and the oxidative stability index (p < 0.05). This study demonstrates that effective controlled release antioxidant packaging could be obtained by using MCNF nanofiller, which leads to prolonged activity and an extended shelf-life in fatty foods. PMID:25013987

  18. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    SciTech Connect

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  19. Bound Phenolics of Quinoa Seeds Released by Acid, Alkaline, and Enzymatic Treatments and Their Antioxidant and α-Glucosidase and Pancreatic Lipase Inhibitory Effects.

    PubMed

    Tang, Yao; Zhang, Bing; Li, Xihong; Chen, Peter X; Zhang, Hua; Liu, Ronghua; Tsao, Rong

    2016-03-01

    Unextractable phenolics from plant foods and their role in health benefits have become increasingly important. Meal residues of three quinoa seeds free of fat and extractable phenolics were subjected to acid, alkaline, and enzymatic hydrolyses. The total and individual phenolic compounds released were analyzed, and 19 phenolics, predominantly phenolic acids and several flavonoids, were identified. The concentration of bound phenolics was highest in black quinoa followed by red and white, regardless of the hydrolysis method. Higher phenolic contents also showed stronger antioxidant activities and inhibition of α-glucosidase and pancreatic lipase activities. Carbohydrases, that is, pectinase, xylanase and feruloyl esterase, which effectively liberated bound phenolics are known to be secreted by colonic bacteria, suggesting potential antioxidant and anti-inflammatory effects by these compounds in the large intestine during colonic fermentation. These results can also be applied to treat foods high in bound phenolics to enhance bioaccessibility. PMID:26853559

  20. Valproic acid pharmacokinetics in the mouse following controlled-release of pharmacologic and toxic doses via novel implantable and refillable drug reservoirs.

    PubMed

    Nau, H; Finley, P; Williams, J; Brendel, K

    1983-01-01

    Novel drug reservoirs are described which, after their implantation under mouse skin, continuously released organic liquids such as the anti-epileptic drug valproic acid at preselected rates for periods up to several weeks. The liquids, which were filled into the reservoirs, diffused through silastic membranes. The area and thickness of these membranes determined the administered dose. Administration of the anti-epileptic drug valproic acid at various selected doses resulted in persistent drug concentrations spanning from subtherapeutic to toxic levels. The drug reservoirs were easily refillable in situ which greatly extended the duration of the experiment. The dose administered could be determined within 5-15 per cent (rel. S.D.). It is suggested that the maintenance of persistent drug levels in small laboratory animals may be an appropriate model for the pharmacological and toxicological study of those compounds with short half-lives and high clearance rates in these species. PMID:6411139

  1. The transcriptional activator GaaR of Aspergillus niger is required for release and utilization of d-galacturonic acid from pectin.

    PubMed

    Alazi, Ebru; Niu, Jing; Kowalczyk, Joanna E; Peng, Mao; Aguilar Pontes, Maria Victoria; van Kan, Jan A L; Visser, Jaap; de Vries, Ronald P; Ram, Arthur F J

    2016-06-01

    We identified the d-galacturonic acid (GA)-responsive transcriptional activator GaaR of the saprotrophic fungus, Aspergillus niger, which was found to be essential for growth on GA and polygalacturonic acid (PGA). Growth of the ΔgaaR strain was reduced on complex pectins. Genome-wide expression analysis showed that GaaR is required for the expression of genes necessary to release GA from PGA and more complex pectins, to transport GA into the cell, and to induce the GA catabolic pathway. Residual growth of ΔgaaR on complex pectins is likely due to the expression of pectinases acting on rhamnogalacturonan and subsequent metabolism of the monosaccharides other than GA. PMID:27174630

  2. Protolichesterinic Acid, Isolated from the Lichen Cetraria islandica, Reduces LRRC8A Expression and Volume-Sensitive Release of Organic Osmolytes in Human Lung Epithelial Cancer Cells.

    PubMed

    Thorsteinsdottir, Unnur Arna; Thorsteinsdottir, Margret; Lambert, Ian Henry

    2016-01-01

    We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces LRRC8A protein expression by 25% and taurine release following osmotic cell swelling (320 → 200 mOsm) by 60%. C75 (20 µg/mL, 24 h), a γ-lactone with a C8 carbon fatty acid chain, reduces VSOAC activity by 30%, i.e. less than PA. Stearic acid (20 µg/mL, 24 h) has no effect on VSOAC. Hence, length of PA's fatty acid chain adds to γ-lactone's inhibitory action. 5-Lipoxygenase (5-LO) activity is essential for swelling-induced activation of VSOAC. PA has no effect on cellular concentration of leukotrienes (5-HETE/LTB4 ) under hypotonic conditions, excluding that PA mediated inhibition of VSOAC involves 5-LO inhibition. A549 cells exposed to the chemotherapeutic drug cisplatin (10 μM, 24 h) reveal signs of apoptosis, i.e. 25% reduction in cell viability as well as 1.3-, 1.5- and 3.3-fold increase in the expression of LRRC8A, Bax (regulator of apoptosis) and p21 (regulator of cell cycle progression), respectively. PA reduces cell viability by 30% but has no effect on p21/Bax expression. This excludes PA as a pro-apoptotic drug in A549 cells. PMID:26549524

  3. Release of a chitosan-hydroxyapatite composite loaded with ibuprofen and acetyl-salicylic acid submitted to different sterilization treatments

    NASA Astrophysics Data System (ADS)

    Larena, A.; Cáceres, D. A.; Vicario, C.; Fuentes, A.

    2004-11-01

    It has been demonstrated that chitosan-hydroxyapatite composite induces osteoconductivity in osseous defects but also could act as drug vehicle. It is important be able to load these composites with short-time life and controlled action anti-inflammatories to reduce or eliminate undesirable inflammatory processes. The goal of the present study is to define the variation between surface properties that this composite experiments as consequence of several sterilization treatments, and application of several pharmaceutical products relating with physical properties. Morphological changes on surface, achieved by polarization and confocal microscopies, thermal and physical properties of chitosan composites and the NSAIDs release process kinetics so as the sterilization treatment effects observed by UV-vis spectroscopy were studied. In this article, it has been demonstrated that the kind of sterilization has no important influence in NSAIDs release in chitosan membranes or composites but differs a little with chitosan membranes no submitted to sterilization treatments.

  4. Acid and reduction stimulated logic "and"-type combinational release mode achieved in DOX-loaded superparamagnetic nanogel.

    PubMed

    Song, Meifang; Xue, Yanan; Chen, Lidi; Xia, Xiaoyang; Zhou, Yang; Liu, Lei; Yu, Bo; Long, Sihui; Huang, Shiwen; Yu, Faquan

    2016-08-01

    A superparamagnetic nanogel featured with a logic "and"-type pH/reduction combinational stimulated release mode was fabricated as a drug delivery system by virtue of parallel crosslinking. The disulfide bond and electrostatic interaction between thiolated alginate (SA-SH) and thiolated/aminated iron oxide nanoparticles (SH-MION-NH2) were employed to achieve the mechanism. The obtained DOX-loaded magnetic nanogel is 122.7±20.3nm in size with superparamagnetism. The combinational conditions of pH5.0/10mM glutathione (GSH) stimulated a significantly high accumulative release. However, either pH7.4/10mM (GSH) or pH5.0 alone induced much low release. This verified the typical logic "and"-type combinationally stimulated release mode. In vitro cytotoxicity tests clearly illustrated the effective selectivity of killing the human cervical cancer cells (HeLa) with IC50 of 1.01μg/mL and the human hepatoma cells (HepG2) with IC50 of 1.57μg/mL but significantly low cytotoxicity to the cercopithecus aethiops kidney cells (Vero). CLSM presented the internationalization of the nanogel into cytoplasm and nuclei with time. In vivo investigation revealed that the selective intratumoral accumulation and antitumor efficacy were considerably advantageous over free DOX whereas low systemic toxicity exhibited up-regulated security as compared to free DOX. Overall, the DOX-loaded magnetic nanogel with enhanced antitumor efficacy and down-regulated adverse effect was a promising nanoplatform for the clinical chemotherapy of malignancy. PMID:27157762

  5. Medium and Long Chain Fatty Acids Differentially Modulate Apoptosis and Release of Inflammatory Cytokines in Human Liver Cells.

    PubMed

    Li, Lumin; Wang, Baogui; Yu, Ping; Wen, Xuefang; Gong, Deming; Zeng, Zheling

    2016-06-01

    Medium chain fatty acids (MCFA) can be more easily absorbed and supply energy more rapidly than long chain fatty acids (LCFA). However, little is known about the inflammatory response by the treatment of MCFA in human liver cells. Thus this study used human liver cells (LO2) to evaluate the effects of MCFA on apoptosis and inflammatory response. Tetrazolim-based colorimetric assay and lactate dehydrogenase assay were used to measure the viability of LO2 cells, isolated spleens and liver cells from BALB/C mice. Inverted fluorescence microscopy and flow cytometry were used to assess the cell apoptosis. Activity of superoxide dismutase and malondialdehyde level were measured to determine the oxidative damage. mRNA or protein levels of classical pro-inflammatory cytokines were analyzed by quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay and western blotting. The results showed that the liver cells treated with the fatty acids at 200 μM for 24 h exhibited good viability. Fatty acids induced inflammatory cytokines at transcriptional and translational levels to a lesser extent than lipopolysaccharide. LCFA (oleic acid) up-regulated tumor necrosis fator-α, monocyte chemoattractant-1 and interleukin-1β while down-regulated IL-6 and IL-8 secretion to a higher extent than MCFA in mRNA and protein levels. These findings suggested that MCFA may induce apoptosis to a less extent and exert more gentle inflammation than LCFA in human liver cells. PMID:27145239

  6. Superabsorbent hydrogels via graft polymerization of acrylic acid from chitosan-cellulose hybrid and their potential in controlled release of soil nutrients.

    PubMed

    Essawy, Hisham A; Ghazy, Mohamed B M; El-Hai, Farag Abd; Mohamed, Magdy F

    2016-08-01

    Superabsorbent polymers fabricated via grafting polymerization of acrylic acid from chitosan (CTS) yields materials that suffer from poor mechanical strength. Hybridization of chitosan with cellulose (Cell) via chemical bonding using thiourea formaldehyde resin increases the flexibility of the produced hybrid (CTS/Cell). The hybridization process and post graft polymerization of acrylic acid was followed using Fourier transform infrared (FTIR). Also, the obtained structures were homogeneous and exhibited uniform surface as could be shown from imaging with scanning electron microscopy (SEM). Thus, the polymers derived from the grafting of polyacrylic acid from (CTS/Cell) gave rise to much more mechanically robust structures ((CTS/Cell)-g-PAA) that bear wide range of pH response due to presence of chitosan and polyacrylic acid in one homogeneous entity. Additionally, the obtained structures possessed greater water absorbency 390, 39.5g/g in distilled water and saline (0.9wt.% NaCl solution), respectively, and enhanced retention potential even at elevated temperatures as revealed by thermogravimetric analysis (TGA). This could be explained by the high grafting efficiency (GE%), 86.4%, and grafting yield (GY%), 750%. The new superabsorbent polymers proved to be very efficient devices for controlled release of fertilizers into the soil which expands their use in agriculture and horticultural applications. PMID:27126169

  7. In-vitro evaluation of biphenylyl acetic acid-beta-cyclodextrin conjugates as colon-targeting prodrugs: drug release behaviour in rat biological media.

    PubMed

    Hirayama, F; Minami, K; Uekama, K

    1996-01-01

    Biphenylyl acetic acid was selectively conjugated to one of the primary hydroxyl groups of beta-cyclodextrin through an ester- or amide-linkage, and the physicochemical properties (aqueous solubility and hydrolysis) were investigated. Aqueous solubility of the conjugates was lower than those of either drug or parent beta-cyclodextrin. The amide conjugate was stable in aqueous solution and in rat biological fluids and gastrointestinal contents. The ester conjugate was hydrolysed to beta-cyclodextrin and biphenylyl acetic acid at moderate rates resulting in a V-shaped rate-pH profile in aqueous solution. The ester conjugate released the drug preferentially when incubated with the contents of caecum or colon, whereas no appreciable drug release was observed on incubation with contents of stomach or intestine, nor on incubation with intestinal or liver homogenates, nor on incubation with rat blood. The present results suggest that the ester-type drug conjugate of beta-cyclodextrin may serve as a colon-targeting prodrug. PMID:8722490

  8. Water-compatible silica sol-gel molecularly imprinted polymer as a potential delivery system for the controlled release of salicylic acid.

    PubMed

    Li, Bin; Xu, Jingjing; Hall, Andrew J; Haupt, Karsten; Tse Sum Bui, Bernadette

    2014-09-01

    Molecularly imprinted polymers (MIPs) for salicylic acid were synthesized and evaluated in aqueous environments in the aim to apply them as drug delivery carriers. One organic MIP and one inorganic MIP based on the sol-gel process were synthesized. The organic MIP was prepared by radical polymerization using the stoichiometric functional monomer, 1-(4-vinylphenyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea, which can establish strong electrostatic interactions with the -COOH of salicylic acid. The sol-gel MIP was prepared with 3-(aminopropyl)triethoxysilane and trimethoxyphenylsilane, as functional monomers and tetraethyl orthosilicate as the crosslinker. While the organic MIPs bound the target specifically in acetonitrile, they exhibited lower binding in the presence of water, although the imprinting factor increased under these conditions, due to reduced non-specific binding. The sol-gel MIP has a high specificity and capacity for the drug in ethanol, a solvent compatible with drug formulation and biomedical applications. In vitro release profiles of the polymers in water were evaluated, and the results were modelled by Fick's law of diffusion and the power law. Analysis shows that the release mechanism was predominantly diffusion-controlled. PMID:25042710

  9. From solution to in-cell study of the chemical reactivity of acid sensitive functional groups: a rational approach towards improved cleavable linkers for biospecific endosomal release.

    PubMed

    Jacques, Sylvain A; Leriche, Geoffray; Mosser, Michel; Nothisen, Marc; Muller, Christian D; Remy, Jean-Serge; Wagner, Alain

    2016-06-01

    pH-Sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for the selective release of therapeutics at their site of action. In this paper, the hydrolytic cleavage of a wide variety of molecular structures that have been reported for their use in pH-sensitive delivery systems was examined. A wide variety of hydrolytic stability profiles were found among the panel of tested chemical functionalities. Even within a structural family, a slight modification of the substitution pattern has an unsuspected outcome on the hydrolysis stability. This work led us to establish a first classification of these groups based on their reactivities at pH 5.5 and their relative hydrolysis at pH 5.5 vs. pH 7.4. From this classification, four representative chemical functions were selected and studied in-vitro. The results revealed that only the most reactive functions underwent significant lysosomal cleavage, according to flow cytometry measurements. These last results question the acid-based mechanism of action of known drug release systems and advocate for the importance of an in-depth structure-reactivity study, using a tailored methodology, for the rational design and development of bio-responsive linkers. PMID:27169758

  10. Stimuli-sensitive hydrogel based on N-isopropylacrylamide and itaconic acid for entrapment and controlled release of Candida rugosa lipase under mild conditions.

    PubMed

    Milašinović, Nikola; Knežević-Jugović, Zorica; Milosavljević, Nedeljko; Lučić Škorić, Marija; Filipović, Jovanka; Kalagasidis Krušić, Melina

    2014-01-01

    Stimuli responsive pH- and temperature-sensitive hydrogel drug delivery systems, as those based on N-isopropylacrylamide (NiPAAm) and itaconic acid (IA), have been attracting much of the attention of the scientific community nowadays, especially in the field of drug release. By adjusting comonomer composition, the matrix is enabled to protect the incorporated protein in the highly acidic environment of upper gastrointestinal tract and deliver it in the neutral or slightly basic region of the lower intestine. The protein/poly(NiPAAm-co-IA) hydrogels were synthetized by free radical crosslinking copolymerization and were characterized concerning their swelling capability, mechanical properties, and morphology. The pore structure and sizes up to 1.90 nm allowed good entrapment of lipase molecules. Model protein, lipase from Candida rugosa, was entrapped within hydrogels upon mild conditions that provided its protection from harmful environmental influences. The efficiency of the lipase entrapment reached 96.7%, and was dependent on the initial concentration of lipase solution. The swelling of the obtained hydrogels in simulated pH and temperature of gastrointestinal tract, the lipase entrapment efficiency, and its release profiles from hydrogels were investigated as well. PMID:24982870

  11. Stimuli-Sensitive Hydrogel Based on N-Isopropylacrylamide and Itaconic Acid for Entrapment and Controlled Release of Candida rugosa Lipase under Mild Conditions

    PubMed Central

    Milašinović, Nikola; Knežević-Jugović, Zorica; Milosavljević, Nedeljko; Lučić Škorić, Marija; Filipović, Jovanka; Kalagasidis Krušić, Melina

    2014-01-01

    Stimuli responsive pH- and temperature-sensitive hydrogel drug delivery systems, as those based on N-isopropylacrylamide (NiPAAm) and itaconic acid (IA), have been attracting much of the attention of the scientific community nowadays, especially in the field of drug release. By adjusting comonomer composition, the matrix is enabled to protect the incorporated protein in the highly acidic environment of upper gastrointestinal tract and deliver it in the neutral or slightly basic region of the lower intestine. The protein/poly(NiPAAm-co-IA) hydrogels were synthetized by free radical crosslinking copolymerization and were characterized concerning their swelling capability, mechanical properties, and morphology. The pore structure and sizes up to 1.90 nm allowed good entrapment of lipase molecules. Model protein, lipase from Candida rugosa, was entrapped within hydrogels upon mild conditions that provided its protection from harmful environmental influences. The efficiency of the lipase entrapment reached 96.7%, and was dependent on the initial concentration of lipase solution. The swelling of the obtained hydrogels in simulated pH and temperature of gastrointestinal tract, the lipase entrapment efficiency, and its release profiles from hydrogels were investigated as well. PMID:24982870

  12. Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

    PubMed

    Niu, Xufeng; Liu, Zhongning; Hu, Jiang; Rambhia, Kunal J; Fan, Yubo; Ma, Peter X

    2016-07-01

    To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects. PMID:26987445

  13. Poly(acrylic acid) modified lanthanide-doped GdVO4 hollow spheres for up-conversion cell imaging, MRI and pH-dependent drug release.

    PubMed

    Kang, Xiaojiao; Yang, Dongmei; Dai, Yunlu; Shang, Mengmeng; Cheng, Ziyong; Zhang, Xiao; Lian, Hongzhou; Ma, Ping'an; Lin, Jun

    2013-01-01

    In this study, multifunctional poly(acrylic acid) modified lanthanide-doped GdVO(4) nanocomposites [PAA@GdVO(4): Ln(3+) (Ln = Yb/Er, Yb/Ho, Yb/Tm)] were constructed by filling PAA hydrogel into GdVO(4) hollow spheres via photoinduced polymerization. The up-conversion (UC) emission colors (green, red and blue) can be tuned by changing the codopant compositions in the matrices. The composites have potential applications as bio-probes for cell imaging. Meanwhile, the hybrid spheres can act as T(1) contrast agents for magnetic resonance imaging (MRI) owing to the existence of Gd(3+) ions on the surface of composites. Due to the nature of PAA, DOX-loaded PAA@GdVO(4):Yb(3+)/Er(3+) system exhibits pH-dependent drug releasing kinetics. A lower pH offers a faster drug release rate. Such character makes the loaded DOX easily released at cancer cells. The cell uptake process of drug-loaded composites was observed by using confocal laser scanning microscopy (CLSM). The results indicate the potential application of the multifunctional composites as theragnostics (effective bimodal imaging probes and pH-responsive drug carriers). PMID:23154448

  14. Effect of preparation route on the degradation behavior and ion releasability of siloxane-poly(lactic acid)-vaterite hybrid nonwoven fabrics for guided bone regeneration.

    PubMed

    Wakita, Takashi; Nakamura, Jin; Ota, Yoshio; Obata, Akiko; Kasuga, Toshihiro; Ban, Seiji

    2011-01-01

    Two types of nonwoven fabric, consisting of siloxane-doped vaterite (SiV) and poly(lactic acid) (PLA), for guided bone regeneration (GBR) were prepared by an electrospinning. One of the fabrics, SiV-PLA(M), was derived from PLA mixed with the solution of SiV dispersed in chloroform. Another one, SiV-PLA(K), was derived from a composite prepared by kneading SiV and PLA while heating at 200°C. The SiV-PLA(K) fabric shows higher degradability in dilute NaOH aq. than the SiV-PLA(M) fabric. To improve the cellular compatibility of the fabric, the fibers were coated with hydroxyapatite (HA) by soaking in simulated body fluid. The HA-coated SiV-PLA(K) fabric showed the release of silicate ions; the amount was reduced by 1/5 to 1/8 compared with that of the HA-coated SiV-PLA(M) fabric, and the excessive release was controlled. The preparation route of kneading at 200°C led to formation of a fabric with degradation behavior and ion releasability effective for bone regeneration. PMID:21415554

  15. Bacterial lipopolysaccharide primes human neutrophils for enhanced release of arachidonic acid and causes phosphorylation of an 85-kD cytosolic phospholipase A2.

    PubMed Central

    Doerfler, M E; Weiss, J; Clark, J D; Elsbach, P

    1994-01-01

    Production of leukotriene B4 (LTB4) by human neutrophils (PMN) in response to different stimuli is increased after pretreatment with lipopolysaccharides (LPS). We have analyzed the steps in arachidonic acid (AA) metabolism affected by LPS by examining release of AA and its metabolites from [3H]AA prelabeled PMN. Pretreatment of PMN for 60 min with up to 1 microgram/ml of LPS alone had no effect, but release of [3H]AA was stimulated up to fivefold during subsequent stimulation with a second agent. In the absence of LPS-binding protein (LBP), priming was maximal after pretreatment of PMN with 10 ng of LPS/ml for 60 min; in the presence of LBP maximal priming occurred within 45 min at 0.1 ng of LPS/ml and within 15 min at 100 ng of LPS/ml. Treatment of PMN with 10 ng of LPS/ml also increased uptake of opsonized zymosan by up to 60%. Phospholipids are the source of released [3H]AA. No release was observed from [14C]oleic acid (OA)-labeled PMN suggesting that phospholipolysis may be specific for [3H]AA-labeled phospholipid pools. Cytosol from PMN primed with LPS contains two to three times the phospholipase A2 (PLA2) activity of control PMN, against 1-palmitoyl-[2-14C]arachidonoyl-phosphatidylcholine. This activity is Ca2+ dependent and dithiothreitol resistant. LPS priming is accompanied by reduced migration during SDS-PAGE of an 85-kD protein, identified as a cytosolic PLA2. The extent and kinetics of this effect of LPS on cPLA2 parallel the priming of [3H]AA release, both depending on LPS concentration either with or without LBP. These findings suggest that priming by LPS of AA metabolism by PMN includes phosphorylation of an AA-phospholipid-selective cytosolic PLA2 that is dissociated from activation until a second stimulus is applied. Images PMID:7512985

  16. 18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling.

    PubMed

    Endo, Jin; Sano, Motoaki; Isobe, Yosuke; Fukuda, Keiichi; Kang, Jing X; Arai, Hiroyuki; Arita, Makoto

    2014-07-28

    N-3 polyunsaturated fatty acids (PUFAs) have potential cardiovascular benefit, although the mechanisms underlying this effect remain poorly understood. Fat-1 transgenic mice expressing Caenorhabditis elegans n-3 fatty acid desaturase, which is capable of producing n-3 PUFAs from n-6 PUFAs, exhibited resistance to pressure overload-induced inflammation and fibrosis, as well as reduced cardiac function. Lipidomic analysis revealed selective enrichment of eicosapentaenoic acid (EPA) in fat-1 transgenic bone marrow (BM) cells and EPA-metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) in fat-1 transgenic macrophages. BM transplantation experiments revealed that fat-1 transgenic BM cells, but not fat-1 transgenic cardiac cells, contributed to the antiremodeling effect and that the 18-HEPE-rich milieu in the fat-1 transgenic heart was generated by BM-derived cells, most likely macrophages. 18-HEPE inhibited macrophage-mediated proinflammatory activation of cardiac fibroblasts in culture, and in vivo administration of 18-HEPE reproduced the fat-1 mice phenotype, including resistance to pressure overload-induced maladaptive cardiac remodeling. PMID:25049337

  17. pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response.

    PubMed

    Liu, Qi; Chen, Xiaoming; Jia, Jilei; Zhang, Weifeng; Yang, Tingyuan; Wang, Lianyan; Ma, Guanghui

    2015-05-26

    In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) NPs with rapid antigen intracellular release behavior in APCs. The NPs, which had thin shells and large inner space, contain ammonium bicarbonate (NH4HCO3), which could regulate release in endosomes and lysosomes, acting as an antigen release promoter in dendritic cells (DCs), and were coencapsulated with antigen (ovalbumin, OVA). Hydrogen ions (H(+)) in DC endosomes and lysosomes (pH ∼5.0 and 6.5) could react with NH4HCO3 to generate NH3 and CO2, which broke NPs and released antigens. After uptake by DCs, antigens encapsulated in pH-responsive PLGA NPs could escape from lysosomes into the cytoplasm and be cross-presented. Moreover, the NPs induced up-regulation of co-stimulatory molecules and stimulated cytokine production. Mouse immunization with pH-responsive PLGA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-γ and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity. The NPs also improved generation of memory T cells to protect against reinfection. Thus, pH-responsive PLGA NPs, which induced strong cellular immune responses and offered antibody protection, could be potentially useful as effective vaccine delivery and adjuvant systems for the therapy of intracellular infectious diseases and virus infection. PMID:25898266

  18. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

    PubMed Central

    Luo, Yuling; Liu, Zhongbing; Zhang, Xiaoqin; Huang, Juan; Yu, Xin; Li, Jinwei; Xiong, Dan; Sun, Xiaoduan; Zhong, Zhirong

    2016-01-01

    The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy. PMID:27471381

  19. Upper critical solution temperature behavior of cinnamic acid and polyethyleneimine mixture and its effect on temperature-dependent release of liposome.

    PubMed

    Guo, Huangying; Kim, Jin-Chul

    2015-10-15

    The mixture of polyethyleneimine (PEI) and cinnamic acid (CA) in HEPES buffer (pH 7.0) exhibited an upper critical solution temperature in the temperature range of 20-50 °C. CA would be electrostatically conjugated with PEI and the PEI-CA conjugate is thought to act as a thermo-sensitive polymer. On the optical microscope image of PEI/CA mixture, microparticles were found at 25 °C, disappeared when heated to 50 °C, and formed again upon cooling to 25 °C. PEI-CA conjugate was immobilized on the surface of egg phosphatidylcholine (EPC) liposome by adding PEI to the suspension of liposome incorporating CA. The size and the zeta potential of the liposome markedly increased by cooling the liposomal suspension from 50 °C to 20 °C. This could be ascribed to the cooling-induced self-assembling property of PEI-CA conjugate. The release profile of Rhodamine B base from liposome incorporating CA with PEI was investigated while the liposome suspension of 50 °C was exposed to the release medium of 20 °C, 30 °C, 40 °C and 50 °C. The release degree was higher at a lower temperature. When exposed to a lower temperature (20 °C, 30 °C, 40 °C), PEI-CA could be self-assembled and change its configuration on the surface of liposome, promoting the release from the liposome. PMID:26283281

  20. Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I.

    PubMed Central

    Castro-Alamancos, M A; Torres-Aleman, I

    1993-01-01

    We tested the possibility that insulin-like growth factor I (IGF-I) acts as a neuromodulator in the adult cerebellar cortex since previous observations indicated that IGF-I is located in the olivo-cerebellar system encompassing the inferior olive and Purkinje cells. We found that conjoint administration of IGF-I and glutamate through a microdialysis probe stereotaxically implanted into the cerebellar cortex and deep cerebellar nuclei greatly depressed the release of gamma-aminobutyric acid (GABA), which normally follows a glutamate pulse. This inhibition was dose-dependent and long-lasting. Moreover, the effect was specific for glutamate since KCl-induced GABA release was not modified by IGF-I. Basic fibroblast growth factor, another growth-related peptide present in the cerebellum, did not alter the response of GABA to glutamate stimulation. In addition, electrical stimulation of the inferior olivary complex significantly raised IGF-I levels in the cerebellar cortex. Interestingly, when the inferior olive was stimulated in conjunction with glutamate administration, GABA release by cerebellar cells in response to subsequent glutamate pulses was depressed in a manner reminiscent of that seen after IGF-I. These findings indicate that IGF-I produces a long-lasting depression of GABA release by Purkinje cells in response to glutamate. IGF-I might be present in climbing fiber terminals and/or cells within the cerebellar cortex and thereby might affect Purkinje cell function. Whether this IGF-I-induced impairment of glutamate stimulation of Purkinje cells underlies functionally plastic processes such as long-term depression is open to question. Images Fig. 1 PMID:8346260

  1. 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

  2. Paclitaxel distribution in poly(ethylene glycol) / poly(lactide-co-glycolic acid) blends and its release visualized by coherent anti-Stokes Raman scattering microscopy

    PubMed Central

    Kang, Eunah; Robinson, Joshua; Park, Kinam; Cheng, Ji-Xin

    2007-01-01

    Mechanisms underlying the release of paclitaxel (PTX) from poly(ethylene glycol)/poly(lactic-co-glycolic acid) (PEG/PLGA) blends were investigated by coherent anti-Stokes Raman scattering (CARS) microscopy. PLGA, PEG, and PTX were selectively imaged by using the resonant CARS signal from the CH3, CH2, and aromatic CH stretch vibrations, respectively. Phase segregation was observed in PLGA films containing 10 to 40 wt.% PEG in the absence of PTX loading. The PEG phase existed in the form of crystalline fibers in the (8:2, weight ratio) and (7:3) PLGA/PEG films. CARS observation indicated that PTX preferentially partitioned into the PEG domains in the (9:1) and (8:2) PLGA/PTX films, but exhibited a uniform mixing with both PLGA and PEG in the (7:3) PLGA/PEG film. The solid dispersion of PTX into PEG domains was attributed to a strong interaction between PTX and PEG, supported by the disappearance of PEG crystallization in the PTX-loaded PLGA/PEG film evidenced through X-ray diffraction analysis. PTX release was induced by exposing the film to an aqueous solution and monitored in real time by CARS and two-photon fluorescence microscopy. Fast dissolution of both PEG and PTX was observed at the film surface. Upon infiltration of water into the film, the PEG domains rearranged into ring structures enriched by both PTX and PEG. The CARS data provided a visual evidence explaining the accelerated burst release followed by more sustained release of PTX from the PLGA/PEG films as measured by HPLC. PMID:17574291

  3. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo.

    PubMed

    Luo, Yuling; Liu, Zhongbing; Zhang, Xiaoqin; Huang, Juan; Yu, Xin; Li, Jinwei; Xiong, Dan; Sun, Xiaoduan; Zhong, Zhirong

    2016-01-01

    The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger-Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy. PMID:27471381

  4. Sustained ibuprofen release using composite poly(lactic-co-glycolic acid)/titanium dioxide nanotubes from Ti implant surface.

    PubMed

    Jia, Huiying; Kerr, Lei L

    2013-07-01

    Developing coatings on implant surface as drug carriers can reduce organ toxicity and effectively deliver drug locally to the target compared with the oral approach. Titanium dioxide (TiO2) nanotube has great potential for this application for widely used Ti implants because of its high surface area, ability to promote bone growth, and biocompatibility. However, there are two issues needed to be solved before further advancing TiO2 nanotubes technology as drug carriers: uncontrolled drug release and poor mechanical properties. In this study, a drug carrier using a composite of biodegradable polymer/TiO2 nanotubes is engineered. Ibuprofen is selected as a concept drug because it is a commonly used anti-inflammatory, fever, and pain-reducing drug. In addition, ibuprofen has a very short plasma half-life of only 1-3 h. A simple characterization method is developed to investigate the infiltration of polymer into TiO2 nanotubes. Good infiltration was observed of polymer into TiO2 nanotubes. The synthesized drug carrier demonstrated much better sustained drug release profiles for ibuprofen of 5 days (low-molecular-weight polymer) and 9 days (high-molecular-weight polymer) compared with 30 min of pure TiO2 nanotubes. The drug carrier also exhibited much improved mechanical strength and flexibility compared with pure TiO2 nanotubes. PMID:23657983

  5. Genetic analysis of L123 of the tRNA-mimicking eukaryote release factor eRF1, an amino acid residue critical for discrimination of stop codons

    PubMed Central

    Saito, Kazuki; Ito, Koichi

    2015-01-01

    In eukaryotes, the tRNA-mimicking polypeptide-chain release factor, eRF1, decodes stop codons on the ribosome in a complex with eRF3; this complex exhibits striking structural similarity to the tRNA–eEF1A–GTP complex. Although amino acid residues or motifs of eRF1 that are critical for stop codon discrimination have been identified, the details of the molecular mechanisms involved in the function of the ribosomal decoding site remain obscure. Here, we report analyses of the position-123 amino acid of eRF1 (L123 in Saccharomyces cerevisiae eRF1), a residue that is phylogenetically conserved among species with canonical and variant genetic codes. In vivo readthrough efficiency analysis and genetic growth complementation analysis of the residue-123 systematic mutants suggested that this amino acid functions in stop codon discrimination in a manner coupled with eRF3 binding, and distinctive from previously reported adjacent residues. Furthermore, aminoglycoside antibiotic sensitivity analysis and ribosomal docking modeling of eRF1 in a quasi-A/T state suggested a functional interaction between the side chain of L123 and ribosomal residues critical for codon recognition in the decoding site, as a molecular explanation for coupling with eRF3. Our results provide insights into the molecular mechanisms underlying stop codon discrimination by a tRNA-mimicking protein on the ribosome. PMID:25897120

  6. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    PubMed Central

    Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Bin Hussein, Mohd Zobir; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2014-01-01

    The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG. PMID:24737969

  7. Differential involvement of protein kinase C in transmitter release and response to excitatory amino acids in cultured cerebellar neurons.

    PubMed

    Eboli, M L; Ciotti, M T; Mercanti, D; Calissano, P

    1993-02-01

    Cerebellar granule cells cultured in the presence of a differentiating factor isolated from rabbit serum exhibit, at variance with those cultured in fetal calf serum, an almost complete resistance to excitatory aminoacid (EAA)-induced cytotoxicity. We investigated the behaviour of protein kinase C (PKC), strongly implicated in EAA cytotoxicity, in the two types of culture. Phorbol esters, used to monitor the enzyme, enhanced the depolarization-evoked release of D-[3H]aspartate, but less effectively in factor-conditioned cells. EAAs increased phorbol esters binding in both cultures, but the effect was briefly lasting in factor-conditioned cells. The different behaviour of PKC is postulated to be causally related to different response to EAA of the cultures. PMID:8097287

  8. Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization.

    PubMed

    Alvarado, H L; Abrego, G; Souto, E B; Garduño-Ramirez, M L; Clares, B; García, M L; Calpena, A C

    2015-06-01

    The aim of the present study was to design and optimize a nanoemulsion for dermal administration of mixtures of natural or synthetic pentacyclic triterpenes with recognized anti-inflammatory activity. The composition of the developed nanoemulsions was obtained from pseudo-ternary phase diagrams, composed of castor oil as the oil phase, labrasol as the surfactant, transcutol-P as co-surfactant and propylene glycol as the aqueous phase. Different ratios of surfactant/co-surfactant mixture (Smix) (4:1, 3:1, 2:1, 1:1, 1:2 and 1:4) were produced, and Smix 4:1 was chosen based on the greater area of optimal nanoemulsion conditions. Two different nanoemulsions of mean droplet size below 600 nm were produced, loading mixtures of natural or synthetic pentacyclic triterpenes, respectively. The viscosity of nanoemulsion containing natural pentacyclic triterpenes was 51.97±4.57 mPas and that loaded with synthetic mixtures was 55.33±0.28 mPas. The studies of release and skin permeation were performed using Franz diffusion cells, adjusting the release kinetics of both formulations to Korsmeyer-Peppas model. No significant differences in permeation parameters between the two nanoemulsions were observed. The amount of drug retained in the skin was higher than the amount of drug that has permeated, favoring a local action. The results of the in vivo tests demonstrated that the developed formulations were not toxic and not irritant to the skin. The formulation loading a mixture of natural triterpenes showed greater ability to inhibit inflammation than that loading the synthetic mixture. The findings clearly corroborate the added value of o/w nanoemulsions for dermal delivery of pentacyclic triterpenes. PMID:25899842

  9. Evidence that the branched-chain amino acid L-valine prevents exercise-induced release of 5-HT in rat hippocampus.

    PubMed

    Gomez-Merino, D; Béquet, F; Berthelot, M; Riverain, S; Chennaoui, M; Guezennec, C Y

    2001-07-01

    The branched-chain amino acid L-valine competes with tryptophan for transport into the brain and has previously been shown to decrease brain 5-HT synthesis. The purpose of this study was to assess, using a combined venous catheterization and in vivo microdialysis method, the effect of pre-exercise L-valine administration on 5-hydroxytryptamine (5-HT) metabolism in the ventral hippocampus of rats submitted to an acute intensive treadmill running (120 min at 25 m x min(-1) followed by 150 min of recovery). The presented results include measurement of extracellular tryptophan (TRP), the 5-HT precursor, and extracellular 5-hydroxyindoleacetic acid (5-HIAA), the 5-HT metabolite. The data clearly demonstrate that exercise induces 5-HT release in the rat hippocampus: in control group, hippocampal 5-HT levels increase from 123.7 +/- 6.4% at the end of exercise to 133.9 +/- 6.4% after 60 min of recovery. Moreover, two hours of intensive running induced significant increases both in extracellular TRP levels (from 120 min of exercise to 30 min of recovery) and 5-HIAA levels (from 90 min of exercise to 90 min of recovery). Pre-exercise administration of L-valine prevents significantly the exercise-induced 5-HT release: 5-HT levels are maintained to baseline during exercise and recovery. With regard to the competitive effect of L-valine with TRP, we could observe a treatment-induced decrease in brain TRP levels (from 120 min of exercise to the end of recovery). Besides, L-valine does not prevent exercise-induced increase in 5-HIAA levels. The present study evidences that an acute intensive exercise stimulates 5-HT metabolism in the rat hippocampus, and that a pre-exercise administration of L-valine prevents, via a limiting effect on 5-HT synthesis, exercise-induced 5-HT release. This study provides some anwers to previous human and animal investigations, showing physiological and psychological benefits of branched-chain amino acids supplementation on performance. PMID:11510866

  10. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

    PubMed

    Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2016-06-01

    Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine. PMID:26377354

  11. Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

    PubMed

    Ruiz, J M; Busnel, J P; Benoît, J P

    1990-09-01

    The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes. PMID:2235892

  12. Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

    PubMed Central

    2013-01-01

    Background Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6–24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process. Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB. Result An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The

  13. The Cytolytic Amphipathic β(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma

    PubMed Central

    Eike, Liv-Marie; Mauseth, Brynjar; Camilio, Ketil André; Rekdal, Øystein; Sveinbjørnsson, Baldur

    2016-01-01

    In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated cells. The use of a murine melanoma model demonstrated that the majority of animals treated with intratumoural injections of LTX-401 showed complete and long-lasting remission. Taken together, these results demonstrate the potential of LTX-401 as an immunotherapeutic agent for the treatment of solid tumors. PMID:26881822

  14. Direct photo-patterning of hyaluronic acid baits onto a fouling-release perfluoropolyether surface for selective cancer cell capture and immobilization.

    PubMed

    Credi, Caterina; De Marco, Carmela; Molena, Elena; Nava, Michele M; Raimondi, Manuela T; Levi, Marinella; Turri, Stefano

    2016-05-01

    A simple photolithographic process for directly patterning glycidyl methacrylate modified hyaluronic acid features onto UV curable perfluoropolyether-based surfaces is presented. Due to the versatility of the developed method, HA spotted areas with different geometrical features could be rapidly and inexpensively designed. In addition, the excellent antifouling and fouling-release properties of the substrates enabled direct HA baits photo-grafting onto PFPEs without further surface passivation or chemical modification to avoid not specific adsorption. The aim of the study was to locally switch the surface properties of the PFPEs from cells and protein repulsive to adherent. Particularly, we exploited HA well-known preferential interactions with CD44 transmembrane receptors to selectively immobilize cancer cells. Living cell arrays offer a higher-resolution visualization of HA-CD44 interactions and may provide a deep insight into understanding molecular mechanisms needed to develop selective therapies and diagnosis against tumor growth. PMID:26952441

  15. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30-84.

    PubMed

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J; Pierson, Leland S; Pierson, Elizabeth A

    2016-01-01

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30-84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surface-attached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30-84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30-84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage-derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30-84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities. PMID:26812402

  16. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

    PubMed Central

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J.; Pierson, Leland S.; Pierson, Elizabeth A.

    2016-01-01

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surface-attached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage-derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities. PMID:26812402

  17. The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

    DOE PAGESBeta

    Wang, Dongping; Yu, Jun Myoung; Dorosky, Robert J.; Pierson, Leland S.; Pierson, Elizabeth A.

    2016-01-26

    Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surfaceattached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conductedmore » comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage- derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities.« less

  18. Micron- and nano-sized poly(N-isopropylacrylamide-co-acrylic acid) latex syntheses and their applications for controlled drug release.

    PubMed

    Lue, Shingjiang Jessie; Chen, Bo-Wei; Shih, Chao-Ming; Chou, Feng-Yi; Lai, Jui-Yang; Chiu, Wen-Yen

    2013-08-01

    Thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) latex particles were prepared with and without sodium dodecyl sulfate (SDS) surfactant via an emulsion polymerization method. The P(NIPAAm-co-AAc) latex particle sizes were approximately 1.1 microm without SDS addition and the particle sizes were in the nanometer range (59 nm) with SDS at its critical micelle concentration (CMC) of 8 mM. We propose a scheme to demonstrate how the SDS concentration affects the synthesized latex particle size. The lower critical solution temperature (LCST) was hardly influenced by the SDS level but increased with the AAc concentration. The PNIPAAm-co-AAc latex particles were employed as thermo-sensitive drug carriers and 4-acetamidophenol was loaded to study the drug release rates from the nano-gels. The effective drug diffusion coefficients within the nano-gels varied as a function of particle size, AAc content, and temperature. The smaller or AAc-rich hydrogel particles provided sustainable drug release property and have potential use in biomedical applications. PMID:23882758

  19. Electrically controlled release of benzoic acid from poly(3,4-ethylenedioxythiophene)/alginate matrix: effect of conductive poly(3,4-ethylenedioxythiophene) morphology.

    PubMed

    Paradee, Nophawan; Sirivat, Anuvat

    2014-08-01

    A drug-loaded conductive polymer/hydrogel blend, benzoic acid-loaded poly(3,4-ethylenedioxythiophene/alginate (BA-loaded PEDOT/Alg) hydrogel, was used as a carrier/matrix for an electrical stimuli transdermal drug delivery system (TDDS). The effects of cross-linking ratio, PEDOT particle size, and electric field strength on the release mechanism and the diffusion coefficient (D) of BA were examined by using a modified Franz-diffusion cell. The diffusion scaling exponent value of BA is close to 0.5 which refers to the diffusion controlled mechanism, or the Fickian diffusion as the BA release mechanism. The D increased when there was a decrease in the cross-linking ratio due to the mesh size-hindering effect. When increasing electric field strength, the D of BA-loaded PEDOT/Alg hydrogel increased because the cathode-BA(-) electrorepulsion, electroinduced alginate expansion, and PEDOT electroneutralization simultaneously occurred. The highest D belonged to a blend with the smallest PEDOT particle and highest electrical conductivity. The D of BA was a function of the matrix mesh size except when drug size/mesh size was lower than 2.38 × 10(-3), where D of BA became mesh size independent as the matrix mesh size was extremely large. Thus, the fabricated conductive polymer hydrogel blends have a great potential to be used in TDDS under electrical stimulation. PMID:25059579

  20. Exovascular application of epigallocatechin-3-O-gallate-releasing electrospun poly(L-lactide glycolic acid) fiber sheets to reduce intimal hyperplasia in injured abdominal aorta.

    PubMed

    Lee, Mi Hee; Kwon, Byeong-ju; Koo, Min-Ah; Jang, Eui Hwa; Seon, Gyeung Mi; Park, Jong-Chul

    2015-09-01

    Intimal hyperplasia is an excessive ingrowth of tissue resulting in chronic structural lesions commonly found at sites of atherosclerotic lesions, arterial angioplasty, vascular graft anastomoses, and other vascular abnormalities. Epigallocatechin-3-O-gallate (EGCG) was shown to elicit antioxidant, anti-proliferative, and anti-thrombogenic effects. In this study, we used an electrospinning technique to synthesize EGCG-eluting biodegradable poly(L-lactide glycolic acid) (PLGA) fiber sheets for local delivery of EGCG and investigated the effect of their exovascular application on intimal hyperplasia following balloon-induced abdominal aorta injury in a rabbit experimental model. The morphology of the composite sheets was characterized using scanning electron microscopy and Fourier transform-infrared spectroscopy. EGCG was loaded and dispersed into the PLGA-based electrospun fibers. The EGCG-loaded PLGA sheets exhibited sustained EGCG release following the initial 24 h of burst release in phosphate-buffered saline. In vivo studies demonstrated significant inhibition of intimal hyperplasia following the application of the EGCG-eluting electrospun PLGA fiber sheets, compared with vehicle PLGA controls. In conclusion, our results show that exovascular application of EGCG-eluting PLGA electrospun fiber sheets may provide a useful system for the effective local delivery of drugs for the prevention of intimal hyperplasia. PMID:26391656

  1. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells.

    PubMed

    Varshosaz, Jaleh; Jahanian-Najafabadi, Ali; Ghazzavi, Jila

    2016-08-01

    The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs. PMID:27463791

  2. Localization of CdSe/ZnS quantum dots in the lysosomal acidic compartment of cultured neurons and its impact on viability: potential role of ion release.

    PubMed

    Corazzari, Ingrid; Gilardino, Alessandra; Dalmazzo, Simona; Fubini, Bice; Lovisolo, Davide

    2013-03-01

    CdSe Quantum Dots (QDs) are increasingly being employed in both industrial applications and biological imaging, thanks to their numerous advantages over conventional organic and proteic fluorescent markers. On the other hand a growing concern has emerged that toxic elements from the QDs core would render the nanoparticles harmful to cell cultures, animals and humans. The interaction between QDs and neuronal cells in particular needs to be carefully evaluated, since nanoparticles could access the nervous system by several pathways, including the olfactory epithelium, even if no data are presently available about QDs. The pH of the environment to which the nanoparticles are exposed may play a crucial role in the stability of QDs coating. For this reason we investigated the release of metal ions from CdSe/ZnS QDs in artificial media reproducing the cytosolic and lysosomal cellular compartments characterized respectively by a neutral and an acidic pH. In the latter significant amounts of both Cd(2+) and Zn(2+) were released. We provide evidence that these QDs are internalized in the GT1-7 neuronal cell line and located in the lysosomal compartment. These findings can be related to a slight but significant reduction in cell survival and proliferation. PMID:23274769

  3. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release.

    PubMed

    D'Aniello, A; Di Fiore, M M; Fisher, G H; Milone, A; Seleni, A; D'Aniello, S; Perna, A F; Ingrosso, D

    2000-04-01

    Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D-Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D-Asp-induced LH secretion from the pituitary gland. Compared to D-Asp, NMDA elicits its hormone release action at concentrations approximately 100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D-Asp by an S-adenosylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase. PMID:10744627

  4. Effect of hypophysectomy and growth hormone replacement on hypothalamic growth hormone-releasing factor messenger ribonucleic Acid levels.

    PubMed

    Eccleston, L M; Powell, J F; Clayton, R N

    1991-12-01

    Abstract The mechanisms by which the pituitary gland, and growth hormone (GH) in particular, affect growth hormone-releasing factor (GRF) gene expression have been addressed using the technique of in situ hybridization. Anatomically matched sections through the mediobasal hypothalamus of control and hypophysectomized male rats, with or without GH hormone replacement, were analysed to obtain information on GRF mRNA levels within the arcuate nucleus and around the ventromedial hypothalamus. Hypophysectomy resulted in a 70% increase in the amount of GRF mRNA per cell (P<0.001), within neurons in the arcuate nucleus. GH replacement and T4 replacement separately partially attenuated this increase (GH replacement P< 0.001 versus hypophysectomy, T4 replacement P<0.05 versus hypophysectomy). Additionally, after hypophysectomy there was an 80% increase in the number of cells expressing the GRF gene in neurons around the ventromedial hypothalamus, when compared to shamoperated controls (P<0.01). Both GH and T4 replacement separately partially attenuated this phenomenon (P<0.01 versus hypophysectomized animals). Hypothyroidism alone did not affect GRF mRNA levels in either the arcuate nucleus or in the area surrounding the ventromedial hypothalamus. These results show that hypophysectomy increases GRF mRNA levels in two separate ways: by increasing the amount of mRNA produced per cell within the arcuate nucleus, and by increasing the number of cells expressing the gene in the area surrounding the ventromedial hypothalamus. This increase in the number of GRF mRNA-containing cells after hypophysectomy could result from the recruitment of neurons which previously did not express the GRF gene, and may reflect the plasticity of the adult central nervous system in response to a changing endocrine environment. This could represent part of a sensor mechanism to drive the production of GRF in the arcuate nucleus in response to extreme disruption of the GRF/ GH feedback loop. PMID

  5. Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil.

    PubMed

    Ranjha, Nazar M; Ayub, Gohar; Naseem, Shahzad; Ansari, Muhammad Tayyab

    2010-10-01

    In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M(c)), polymer volume fraction in swollen state (V(2s)), number of repeating units between crosslinks (M(r)) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting

  6. A study of the swelling and model protein release behaviours of radiation-formed poly(N-vinyl 2-pyrrolidone-co-acrylic acid) hydrogels

    NASA Astrophysics Data System (ADS)

    Wang, David; Hill, David J. T.; Rasoul, Firas; Whittaker, Andrew K.

    2011-02-01

    Hydrogels were prepared from poly(acrylic acid-co-N-vinyl pyrrolidone), poly(AA-co-VP) and mixtures of poly(AA-co-VP) and poly(ethylene oxide), PEO, by gamma radiolysis of aqueous solutions of the AA and VP monomers containing ethylene glycol dimethacrylate, EGDMA, as crosslinker and PEO. The AA/VP composition range of the poly(AA-co-VP) was XAA 0.7-0.9. The swelling behaviours of the hydrogels from the dry state were investigated in water (pH 6.5) and 50 mM 4-(2-hydroxyethyl)piperazine-1-ethylsulfonic acid buffer, HEPES buffer, at pH 7.4 and 295 K. The effects of poly(AA-co-VP) composition, crosslinker mole fraction and the presence of PEO on the equilibrium swelling ratio for the gels was examined. The kinetics of the release of a model protein, horseradish peroxidase, HRP, from the hydrogels in water were also studied at 295 K.

  7. Ascorbic Acid

    MedlinePlus

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  8. Secreted Fungal Effector Lipase Releases Free Fatty Acids to Inhibit Innate Immunity-Related Callose Formation during Wheat Head Infection[W][OPEN

    PubMed Central

    Blümke, Antje; Falter, Christian; Herrfurth, Cornelia; Sode, Björn; Bode, Rainer; Schäfer, Wilhelm; Feussner, Ivo; Voigt, Christian A.

    2014-01-01

    The deposition of the (1,3)-β-glucan cell wall polymer callose at sites of attempted penetration is a common plant defense response to intruding pathogens and part of the plant’s innate immunity. Infection of the Fusarium graminearum disruption mutant Δfgl1, which lacks the effector lipase FGL1, is restricted to inoculated wheat (Triticum aestivum) spikelets, whereas the wild-type strain colonized the whole wheat spike. Our studies here were aimed at analyzing the role of FGL1 in establishing full F. graminearum virulence. Confocal laser-scanning microscopy revealed that the Δfgl1 mutant strongly induced the deposition of spot-like callose patches in vascular bundles of directly inoculated spikelets, while these callose deposits were not observed in infections by the wild type. Elevated concentrations of the polyunsaturated free fatty acids (FFAs) linoleic and α-linolenic acid, which we detected in F. graminearum wild type-infected wheat spike tissue compared with Δfgl1-infected tissue, provided clear evidence for a suggested function of FGL1 in suppressing callose biosynthesis. These FFAs not only inhibited plant callose biosynthesis in vitro and in planta but also partially restored virulence to the Δfgl1 mutant when applied during infection of wheat spikelets. Additional FFA analysis confirmed that the purified effector lipase FGL1 was sufficient to release linoleic and α-linolenic acids from wheat spike tissue. We concluded that these two FFAs have a major function in the suppression of the innate immunity-related callose biosynthesis and, hence, the progress of F. graminearum wheat infection. PMID:24686113

  9. Controlled-release of tetracycline and lovastatin by poly(d,l-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs

    PubMed Central

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

  10. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

    PubMed

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

  11. Valproic Acid Inhibits the Release of Soluble CD40L Induced by Non-Nucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus Infected Individuals

    PubMed Central

    Davidson, Donna C.; Schifitto, Giovanni; Maggirwar, Sanjay B.

    2013-01-01

    Despite the use of highly active antiretroviral therapies (HAART), a majority of Human Immunodeficiency Virus Type 1 (HIV) infected individuals continually develop HIV – Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistent with this notion, we have previously shown that levels of the inflammatory mediator soluble CD40 ligand (sCD40L) are elevated in the plasma and cerebrospinal fluid (CSF) of HIV infected, cognitively impaired individuals, and that excess sCD40L can contribute to blood brain barrier (BBB) permeability in vivo, thereby signifying the importance of this inflammatory mediator in the pathogenesis of HAND. Here we demonstrate that the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) induces the release of circulating sCD40L in both HIV infected individuals and in an in vitro suspension of washed human platelets, which are the main source of circulating sCD40L. Additionally, EFV was found to activate glycogen synthase kinase 3 beta (GSK3β) in platelets, and we now show that valproic acid (VPA), a known GSK3β inhibitor, was able to attenuate the release of sCD40L in HIV infected individuals receiving EFV, and in isolated human platelets. Collectively these results have important implications in determining the pro-inflammatory role that some antiretroviral regimens may have. The use of antiretrovirals remains the best strategy to prevent HIV-associated illnesses, including HAND, however these drugs have clear limitations to this end, and thus, these results underscore the need to develop adjunctive therapies for HAND that can also minimize the undesired negative effects of the antiretrovirals. PMID:23555843

  12. Synthesis and self-assembly of biodegradable polyethylene glycol-poly (lactic acid) diblock copolymers as polymersomes for preparation of sustained release system of doxorubicin

    PubMed Central

    Alibolandi, Mona; Sadeghi, Fatemeh; Sazmand, Seyed Hossein; Shahrokhi, Seyed Mohammad; Seifi, Mahmoud; Hadizadeh, Farzin

    2015-01-01

    Introduction: The copolymer of polyethylene glycol (PEG) and polyesters has many interesting properties, such as amphiphilicity, biocompatibility, biodegradability, and self-assembly in an aqueous environment. Diblock copolymers of PEG-polyester can form different structures such as micelles, polymersome, capsules or micro-container in an aqueous environment according to the length of their blocks. Materials and Methods: Herein, a series of poly (lactic acid) (PLA) and PEG diblock copolymers were synthesized through the ring-opening polymerization. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The corresponding copolymers were implemented for the formation of polymersome structures using film rehydration method. Impact of methoxy PEG chain length and hydrophobic weight fraction on particle size of polymersomes were studied, and the proper ones were selected for loading of doxorubicin (DOX) via pH gradient method. Results and Discussion: Results obtained from 1HNMR and GPC revealed that microwave irradiation is a simple and reliable method for the synthesis of PEG-PLA copolymers. Further analysis indicated the copolymer with relative molecular weight of PLA to PEG ratios of 3 or fEo ~ 25% produced the smallest size polymersomes. Polymersomes prepared from PEG5000 to PLA15000 were more capable in loading and sustained release of DOX than those prepared from PEG2000 to PLA6000. Conclusion: In conclusion copolymers of PEG/PLA with fOE ~25% and relatively higher molecular weight are more suitable for encapsulation and providing sustained release of DOX. PMID:26258054

  13. An alternative reaction for heme degradation catalyzed by the Escherichia coli O157:H7 ChuS protein: Release of hematinic acid, tripyrrole and Fe(III).

    PubMed

    Ouellet, Yannick H; Ndiaye, Cheikh Tidiane; Gagné, Stéphane M; Sebilo, Anne; Suits, Michael D L; Jubinville, Éric; Jia, Zongchao; Ivancich, Anabella; Couture, Manon

    2016-01-01

    As part of the machinery to acquire, internalize and utilize heme as a source of iron from the host, some bacteria possess a canonical heme oxygenase, where heme plays the dual role of substrate and cofactor, the later catalyzing the cleavage of the heme moiety using O2 and electrons, and resulting in biliverdin, carbon monoxide and ferrous non-heme iron. We have previously reported that the Escherichia coli O157:H7 ChuS protein, which is not homologous to heme oxygenases, can bind and degrade heme in a reaction that releases carbon monoxide. Here, we have pursued a detailed characterization of such heme degradation reaction using stopped-flow UV-visible absorption spectrometry, the characterization of the intermediate species formed in such reaction by EPR spectroscopy and the identification of reaction products by NMR spectroscopy and Mass spectrometry. We show that hydrogen peroxide (in molar equivalent) is the key player in the degradation reaction, at variance to canonical heme oxygenases. While the initial intermediates of the reaction of ChuS with hydrogen peroxide (a ferrous keto π neutral radical and ferric verdoheme, both identified by EPR spectroscopy) are in common with heme oxygenases, a further and unprecedented reaction step, involving the cleavage of the porphyrin ring at adjacent meso-carbons, results in the release of hematinic acid (a monopyrrole moiety identified by NMR spectroscopy), a tripyrrole product (identified by Mass spectrometry) and non-heme iron in the ferric oxidation state (identified by EPR spectroscopy). Overall, the unprecedented reaction of E. coli O157:H7 ChuS provides evidence for a novel heme degradation activity in a Gram-negative bacterium. PMID:26598215

  14. Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 hours after 3-nitropropionic acid induced chemical hypoxia

    PubMed Central

    Akopian, Garnik; Crawford, Cynthia; Beal, M. Flint; Cappelletti, Maurand; Jakowec, Michael W.; Petzinger, Giselle M.; Zheng, Ling; Gheorghe, Stacey L.; Reichel, Carmela M.; Chow, Robert; Walsh, John P

    2008-01-01

    The striatum is particularly sensitive to the irreversible inhibitor of succinate dehyrdrogenase 3-nitropropionic acid (3-NP). In the present study we examined early changes in behavior and dopamine and glutamate synaptic physiology created by a single systemic injection of 3-NP in Fischer 344 rats. Hind limb dystonia was seen 2 hours after 3-NP injections and rats performed poorly on balance beam and rota-rod motor tests 24 hours later. Systemic 3-NP increased NMDA receptor-dependent long-term potentiation (LTP) at corticostriatal synapses over the same time period. The 3-NP induced corticostriatal LTP was not due to increased NMDA receptor number or function, since 3-NP did not change MK-801 binding or NMDA/AMPA receptor current ratios. The LTP seen 24 hours after 3-NP was D1 receptor-dependent and reversed by exogenous addition of dopamine or a D2 receptor agonist to brain slices. High performance liquid chromatography and fast scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected 24 hours earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed by 48 hours. Tyrosine hydroxylase expression was not changed and there was no evidence of striatal cell loss at 24–48 hours after 3-NP exposure. Sprague-Dawley rats showed similar physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity. PMID:18799690

  15. Colon-specific drug delivery based on a cyclodextrin prodrug: release behavior of biphenylylacetic acid from its cyclodextrin conjugates in rat intestinal tracts after oral administration.

    PubMed

    Minami, K; Hirayama, F; Uekama, K

    1998-06-01

    An antiinflammatory drug biphenylylacetic acid (BPAA) as a model drug was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-, and gamma-cyclodextrins (CyDs) through an ester or amide linkage, and the in vivo drug release behavior of these prodrugs in rat gastrointestinal tracts after oral administration was investigated. The CyD prodrugs were stable in rat stomach and small intestine and negligibly absorbed from these tracts. Three to six hours after the oral administration, most of the prodrugs had moved to the cecum and colon. The alpha- and gamma-CyD amide prodrugs were hydrolyzed to the maltose conjugate in the cecum and colon, and these prodrugs and the conjugate were negligibly absorbed. On the other hand, the alpha- and gamma-CyD ester prodrugs produced BPAA in the cecum and colon, and BPAA appeared in the blood after 3-6 h. Both beta-CyD amide and ester prodrugs released only small or negligible amounts of the maltose conjugate or BPAA in the cecum and colon, within 24 h, probably due to the low solubility in the biological media. Further, the antiinflammatory effect of the gamma-CyD ester prodrug was evaluated using the model of carageenan-induced acute edema in rat paw and compared with those of BPAA alone and the BPAA/beta-CyD complex prepared by the kneading method in a molar ratio of 1:1. In the case of the beta-CyD complex, a rapid antiinflammatory response was observed, compared to BPAA alone, because the drug is mainly absorbed from the small intestine after a fast dissolution of the complex. In sharp contrast, the gamma-CyD ester prodrug needed a fairly long lag time to exhibit the drug activity, because BPAA is produced after the prodrug had reached the cecum and colon. The present results clearly suggest that the CyD prodrug approach can provide a versatile means for constructions of not only colon-specific delivery systems but also delayed-release system of certain drugs. PMID:9607948

  16. Synthesis and characterization of pH-sensitive poly(itaconic acid)-poly(ethylene glycol)-folate-poly(l-histidine) micelles for enhancing tumor therapy and tunable drug release.

    PubMed

    Sun, Yuan; Li, Yapeng; Nan, Shuli; Zhang, Liangzi; Huang, Hailong; Wang, Jingyuan

    2015-11-15

    pH responsive intracellular tumor targeting is increasingly investigated as a pathway to trigger the release of anti-tumor drugs once the drug carrier reached the unique acidic environment of the solid tumors or after the drug carrier has been taken up by cells, resulting in the localization of the micelles in the acidic endosomes and lysosomes. Poly(itaconic acid)-poly(ethylene glycol)-folate-poly(l-histidine) (PIA-PEG-FA-PHIS) was synthesized as a carrier for tumor-targeted drug delivery. The micelles were internalized by receptor-mediated endocytosis, and the combination of active targeting and triggered release resulted in apparent cytotoxicity and antitumor activity. The MTT assay showed DOX-loaded micelles had higher and obvious cytotoxicity against Hela cells at pH 5.0 than that at pH 7.4. Cellular uptake experiments revealed that these pH-responsive PIA-PEG-FA-PHIS micelles were taken up in great amounts by receptor-mediated endocytosis and delivered to lysosomes, triggering release of DOX into the cytoplasm. These indicated that the PIA-PEG-FA-PHIS micelles could be a promising drug delivery system with preeminent stability for targeting the hydrophobic drugs to cancer cells and releasing DOX in to the cells by sensing the acidic environment of the endosomes for cancer therapy. PMID:26210102

  17. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats.

    PubMed

    Schliephake, Henning; Weich, Herbert A; Dullin, Christian; Gruber, Rudolf; Frahse, Sarah

    2008-01-01

    The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 48 microg rhBMP-2 (Group 1) and blank implants without BMP (Group 0) each on one side of the mandible. Unfilled defects of the same size on the contralateral sides of the mandibles served as empty controls. After 6, 13 and 26 weeks, implants of each group were retrieved from five animals each and submitted to flat panel detector computed tomography. Bone formation and thickness of augmentation was assessed by computer-assisted histomorphometry. In Group 2 significantly more bone was produced than in Group 1. Implants of Group 1 induced significantly more bone than the blank controls only after 6 weeks, whereas the difference was not significant after 13 and 26 weeks. Differences between Group 2 and Group 1 were clearly significant after 26 weeks. The thickness of bone tissue was maintained in Group 2 whereas it decreased in Group 1 and was negligible in Group 0. It is concluded that the PLA implants with 96 microg rhBMP-2 were able to bridge a non-healing defect in the rat mandible and maintained the thickness of an augmented volume. However, continuous supply of osteogenic signals appears to be required to compensate for adverse effects during polymer degradation. PMID:17936352

  18. Hypochlorous acid-induced heme degradation from lactoperoxidase as a novel mechanism of free iron release and tissue injury in inflammatory diseases.

    PubMed

    Souza, Carlos Eduardo A; Maitra, Dhiman; Saed, Ghassan M; Diamond, Michael P; Moura, Arlindo A; Pennathur, Subramaniam; Abu-Soud, Husam M

    2011-01-01

    Lactoperoxidase (LPO) is the major consumer of hydrogen peroxide (H(2)O(2)) in the airways through its ability to oxidize thiocyanate (SCN(-)) to produce hypothiocyanous acid, an antimicrobial agent. In nasal inflammatory diseases, such as cystic fibrosis, both LPO and myeloperoxidase (MPO), another mammalian peroxidase secreted by neutrophils, are known to co-localize. The aim of this study was to assess the interaction of LPO and hypochlorous acid (HOCl), the final product of MPO. Our rapid kinetic measurements revealed that HOCl binds rapidly and reversibly to LPO-Fe(III) to form the LPO-Fe(III)-OCl complex, which in turn decayed irreversibly to LPO Compound II through the formation of Compound I. The decay rate constant of Compound II decreased with increasing HOCl concentration with an inflection point at 100 µM HOCl, after which the decay rate increased. This point of inflection is the critical concentration of HOCl beyond which HOCl switches its role, from mediating destabilization of LPO Compound II to LPO heme destruction. Lactoperoxidase heme destruction was associated with protein aggregation, free iron release, and formation of a number of fluorescent heme degradation products. Similar results were obtained when LPO-Fe(II)-O(2), Compound III, was exposed to HOCl. Heme destruction can be partially or completely prevented in the presence of SCN(-). On the basis of the present results we concluded that a complex bi-directional relationship exists between LPO activity and HOCl levels at sites of inflammation; LPO serve as a catalytic sink for HOCl, while HOCl serves to modulate LPO catalytic activity, bioavailability, and function. PMID:22132121

  19. Hypochlorous Acid-Induced Heme Degradation from Lactoperoxidase as a Novel Mechanism of Free Iron Release and Tissue Injury in Inflammatory Diseases

    PubMed Central

    Saed, Ghassan M.; Diamond, Michael P.; Moura, Arlindo A.; Pennathur, Subramaniam; Abu-Soud, Husam M.

    2011-01-01

    Lactoperoxidase (LPO) is the major consumer of hydrogen peroxide (H2O2) in the airways through its ability to oxidize thiocyanate (SCN−) to produce hypothiocyanous acid, an antimicrobial agent. In nasal inflammatory diseases, such as cystic fibrosis, both LPO and myeloperoxidase (MPO), another mammalian peroxidase secreted by neutrophils, are known to co-localize. The aim of this study was to assess the interaction of LPO and hypochlorous acid (HOCl), the final product of MPO. Our rapid kinetic measurements revealed that HOCl binds rapidly and reversibly to LPO-Fe(III) to form the LPO-Fe(III)-OCl complex, which in turn decayed irreversibly to LPO Compound II through the formation of Compound I. The decay rate constant of Compound II decreased with increasing HOCl concentration with an inflection point at 100 µM HOCl, after which the decay rate increased. This point of inflection is the critical concentration of HOCl beyond which HOCl switches its role, from mediating destabilization of LPO Compound II to LPO heme destruction. Lactoperoxidase heme destruction was associated with protein aggregation, free iron release, and formation of a number of fluorescent heme degradation products. Similar results were obtained when LPO-Fe(II)-O2, Compound III, was exposed to HOCl. Heme destruction can be partially or completely prevented in the presence of SCN−. On the basis of the present results we concluded that a complex bi-directional relationship exists between LPO activity and HOCl levels at sites of inflammation; LPO serve as a catalytic sink for HOCl, while HOCl serves to modulate LPO catalytic activity, bioavailability, and function. PMID:22132121

  20. Wounding-induced Synthesis of Hyaluronic Acid in Organotypic Epidermal Cultures Requires the Release of Heparin-Binding EGF and Activation of the EGF receptor

    PubMed Central

    Monslow, James; Sato, Nobuyuki; Mack, Judith A.; Maytin, Edward V.

    2010-01-01

    Hyaluronic acid (HA), a glycosaminoglycan located between keratinocytes in the epidermis, accumulates dramatically following skin wounding. To study inductive mechanisms, a rat keratinocyte organotypic culture model that faithfully mimics HA metabolism was used. Organotypic cultures were needle-punctured 100 times, incubated for up to 24h, and HA analyzed by histochemical and biochemical methods. By 15 min post-injury, HA levels were elevated 2 fold, increasing to 4-fold by 24 h. HA elevations far from the site of injury suggested the possible involvement of a soluble HA-inductive factor. Media transfer experiments (from wounded cultures to unwounded cultures) confirmed the existence of a soluble factor. From previous evidence, we hypothesized that an EGF-like growth factor might be responsible. This was confirmed as follows: (1), EGF receptor (EGFR) kinase inhibitor (AG1478) completely prevented wounding-induced HA accumulation. (2), Rapid tyrosine-phosphorylation of EGFR correlated nicely with the onset of increased HA synthesis. (3), A neutralizing antibody that recognizes HB-EGF blocked wounding-induced HA synthesis by ≥ 50%. (4), Western analyses demonstrated that release of activated HB-EGF (but not amphiregulin nor EGF) occurs after wounding. In summary, rapid HA accumulation after epidermal wounding occurs via a mechanism requiring cleavage of HB-EGF and activation of EGFR signaling. PMID:19225541

  1. The performance of hybrid titania/silica-derived xerogels as active antifouling/fouling-release surfaces against the marine alga Ulva linza: in situ generation of hypohalous acids.

    PubMed

    Damon, Corey A; Gatley, Caitlyn M; Beres, Joshua J; Finlay, John A; Franco, Sofia C; Clare, Anthony S; Detty, Michael R

    2016-09-13

    Mixed titania/silica xerogels were prepared using titanium tetraisopropoxide (TTIP) and tetraethoxy orthosilicate (TEOS). Xerogel properties were modified by incorporating n-octyltriethoxysilane (C8). The xerogels catalyze the oxidation of bromide and chloride with hydrogen peroxide (H2O2) to produce hypohalous acids at pH 7 and pH 8. The antifouling/ fouling-release performance of a TTIP/C8/TEOS xerogel in the presence and absence of H2O2 was evaluated for the settlement of zoospores of the marine alga Ulva linza and for the removal of sporelings (young plants). In the absence of H2O2, differences in the settlement of zoospores and removal of sporelings were not significant relative to a titanium-free C8/TEOS xerogel. Addition of H2O2 gave a significant reduction in zoospore settlement and sporeling removal relative to the C8/TEOS xerogel and relative to peroxide-free conditions. The impact of TTIP on xerogel characteristics was evaluated by comprehensive contact angle analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy. PMID:27458654

  2. Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

    PubMed

    Cheng, Yung-Hsin; Lin, Feng-Huei; Wang, Chien-Ying; Hsiao, Chen-Yuan; Chen, Hung-Ching; Kuo, Hsin-Yu; Tsai, Ting-Fen; Chiou, Shih-Hwa

    2016-10-01

    Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. PMID:27392289

  3. Variation of S/G Ratio and Lignin Content in a Populus Family Influences the Release of Xylose by Dilute Acid Hydrolysis.

    SciTech Connect

    Davison, Brian H; Drescher, Sadie R; Tuskan, Gerald A; Davis, Dr. Mark F.; Nghiem, Nhuan Phu

    2006-01-01

    Wood samples from second generation Populus cross were shown to have different lignin contents and S/G ratios (S: syringyl-like lignin structures; G: guaiacyl-like lignin structures). The lignin contents varied from 22.7% to 25.8% and the S/G ratio from 1.8 to 2.3. Selected samples spanning these ranges were hydrolyzed with dilute (1%) sulfuric acid to release fermentable sugars. The conditions were chosen for partial hydrolysis of the hemicellulosic fraction to maximize the expression of variation among samples. The results indicated that both lignin contents and S/G ratio significantly affected the yield of xylose. For example, the xylose yield of the 25.8% lignin and 2.3 S/G (hihg lignin, high S/G) sample produced 30% of the theoretical yield, whereas the xylose yield of the 22.7% lignin and 1.8 S/G (low lignin, low S/G) was 55% of the theoretical value. These results indicate that lignin content and composition among genetic variants within a single species can influence the hydrolyzability of the biomass.

  4. A seed coat bedding assay shows that RGL2-dependent release of abscisic acid by the endosperm controls embryo growth in Arabidopsis dormant seeds.

    PubMed

    Lee, Keun Pyo; Piskurewicz, Urszula; Turecková, Veronika; Strnad, Miroslav; Lopez-Molina, Luis

    2010-11-01

    Seed dormancy is an ecologically important adaptive trait in plants whereby germination is repressed even under favorable germination conditions such as imbibition with water. In Arabidopsis and most plant species, dormancy absolutely requires an unidentified seed coat germination-repressive activity and constitutively higher abscisic acid (ABA) levels upon seed imbibition. The mechanisms underlying these processes and their possible relationship are incompletely understood. We developed a "seed coat bedding" assay monitoring the growth of dissected embryos cultured on a layer of seed coats, allowing combinatorial experiments using dormant, nondormant, and various genetically modified seed coat and embryonic materials. This assay, combined with direct ABA measurements, revealed that, upon imbibition, dormant coats, unlike nondormant coats, actively produce and release ABA to repress embryo germination, whatever the embryo origin, i.e., from dormant, nondormant, or never dormant aba seeds, unable to synthesize ABA. The persistent high ABA levels in imbibed dormant seeds requires the permanent expression of the DELLA gene RGL2, where it remains insensitive to gibberellins (GA) unlike in nondormant seeds. These findings present the seed coat as an organ actively controlling germination upon seed imbibition and provide a framework to investigate how environmental factors break seed dormancy. PMID:20956298

  5. Reversible inhibition of proton release activity and the anesthetic-induced acid-base equilibrium between the 480 and 570 nm forms of bacteriorhodopsin.

    PubMed Central

    Boucher, F; Taneva, S G; Elouatik, S; Déry, M; Messaoudi, S; Harvey-Girard, E; Beaudoin, N

    1996-01-01

    In purple membrane added with general anesthetics, there exists an acid-base equilibrium between two spectral forms of the pigment: bR570 and bR480 (apparent pKa = 7.3). As the purple 570 nm bacteriorhodopsin is reversibly transformed into its red 480 nm form, the proton pumping capability of the pigment reversibly decreases, as indicated by transient proton release measurements and proton translocation action spectra of mixture of both spectral forms. It happens in spite of a complete photochemical activity in bR480 that is mostly characterized by fast deprotonation and slow reprotonation steps and which, under continuous illumination, bleaches with a yield comparable to that of bR570. This modified photochemical activity has a correlated specific photoelectrical counterpart: a faster proton extrusion current and a slower reprotonation current. The relative areas of all photocurrent phases are reduced in bR480, most likely because its photochemistry is accompanied by charge movements for shorter distances than in the native pigment, reflecting a reversible inhibition of the pumping activity. PMID:8789112

  6. Effect of a short-term in vitro exposure to the marine toxin domoic acid on viability, tumor necrosis factor-alpha, matrix metalloproteinase-9 and superoxide anion release by rat neonatal microglia

    PubMed Central

    Mayer, Alejandro MS; Hall, Mary; Fay, Michael J; Lamar, Peter; Pearson, Celeste; Prozialeck, Walter C; Lehmann, Virginia KB; Jacobson, Peer B; Romanic, Anne M; Uz, Tolga; Manev, Hari

    2001-01-01

    Background The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total glial population in the brain. We tested the hypothesis that a short-term in vitro exposure to domoic acid, might lead to the activation of rat neonatal microglia and the concomitant release of the putative neurotoxic mediators tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 and-9 (MMP-2 and -9) and superoxide anion (O2-). Results In vitro, domoic acid [10 μM-1 mM] was significantly neurotoxic to primary cerebellar granule neurons. Although neonatal rat microglia expressed ionotropic glutamate GluR4 receptors, exposure during 6 hours to domoic acid [10 μM-1 mM] had no significant effect on viability. By four hours, LPS (10 ng/mL) stimulated an increase in TNF-α mRNA and a 2,233 % increase in TNF-α protein In contrast, domoic acid (1 mM) induced a slight rise in TNF-α expression and a 53 % increase (p < 0.01) of immunoreactive TNF-α protein. Furthermore, though less potent than LPS, a 4-hour treatment with domoic acid (1 mM) yielded a 757% (p < 0.01) increase in MMP-9 release, but had no effect on MMP-2. Finally, while PMA (phorbol 12-myristate 13-acetate) stimulated O2- generation was elevated in 6 hour LPS-primed microglia, a similar pretreatment with domoic acid (1 mM) did not prime O2- release. Conclusions To our knowledge this is the first experimental evidence that domoic acid, at in vitro concentrations that are toxic to neuronal cells, can trigger a release of statistically significant amounts of TNF-α and MMP-9 by brain microglia. These observations are of considerable pathophysiological significance because domoic acid activates rat microglia several days after in vivo administration. PMID:11686853

  7. Experimental Embolization of Rabbit Renal Arteries to Compare the Effects of Poly L-Lactic Acid Microspheres With and Without Epirubicin Release Against Intraarterial Injection of Epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-03-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with 1 mg of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI 1.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemoembolizing material, maintained high local concentrations of the

  8. Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against ntraarterial injection of epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-05-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with l m g of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI l.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemo-embolizing material, maintained high local concentrations of the

  9. Lack of Effects of a Single High-Fat Meal Enriched with Vegetable n-3 or a Combination of Vegetable and Marine n-3 Fatty Acids on Intestinal Peptide Release and Adipokines in Healthy Female Subjects

    PubMed Central

    Narverud, Ingunn; Myhrstad, Mari C. W.; Herzig, Karl-Heinz; Karhu, Toni; Dahl, Tuva B.; Halvorsen, Bente; Ulven, Stine M.; Holven, Kirsten B.

    2016-01-01

    Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3) fatty acids (FAs) from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 FAs with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil, and a combination of linseed and cod liver oil. The test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analyzed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin, which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 FAs from different origin stimulates intestinal peptide release without any difference between the different fat compositions.

  10. Diphenylarsinic Acid Induced Activation of Cultured Rat Cerebellar Astrocytes: Phosphorylation of Mitogen-Activated Protein Kinases, Upregulation of Transcription Factors, and Release of Brain-Active Cytokines.

    PubMed

    Negishi, Takayuki; Matsumoto, Mami; Kojima, Mikiya; Asai, Ryota; Kanehira, Tomoko; Sakaguchi, Fumika; Takahata, Kazuaki; Arakaki, Rina; Aoyama, Yohei; Yoshida, Hikari; Yoshida, Kenji; Yukawa, Kazunori; Tashiro, Tomoko; Hirano, Seishiro

    2016-03-01

    Diphenylarsinic acid (DPAA) was detected as the primary compound responsible for the arsenic poisoning that occurred in Kamisu, Ibaraki, Japan, where people using water from a well that was contaminated with a high level of arsenic developed neurological (mostly cerebellar) symptoms and dysregulation of regional cerebral blood flow. To understand the underlying molecular mechanism of DPAA-induced cerebellar symptoms, we focused on astrocytes, which have a brain-protective function. Incubation with 10 µM DPAA for 96 h promoted cell proliferation, increased the expression of antioxidative stress proteins (heme oxygenase-1 and heat shock protein 70), and induced the release of cytokines (MCP-1, adrenomedullin, FGF2, CXCL1, and IL-6). Furthermore, DPAA overpoweringly increased the phosphorylation of three major mitogen-activated protein kinases (MAPKs) (ERK1/2, p38MAPK, and SAPK/JNK), which indicated MAPK activation, and subsequently induced expression and/or phosphorylation of transcription factors (Nrf2, CREB, c-Jun, and c-Fos) in cultured rat cerebellar astrocytes. Structure-activity relationship analyses of DPAA and other related pentavalent organic arsenicals revealed that DPAA at 10 µM activated astrocytes most effective among organic arsenicals tested at the same dose. These results suggest that in a cerebellum exposed to DPAA, abnormal activation of the MAPK-transcription factor pathway and irregular secretion of these neuroactive, glioactive, and/or vasoactive cytokines in astrocytes can be the direct/indirect cause of functional abnormalities in surrounding neurons, glial cells, and vascular cells: This in turn might lead to the onset of cerebellar symptoms and disruption of cerebral blood flow. PMID:26645585

  11. Cell-free protein synthesis from a release factor 1 deficient Escherichia coli activates efficient and multiple site-specific nonstandard amino acid incorporation.

    PubMed

    Hong, Seok Hoon; Ntai, Ioanna; Haimovich, Adrian D; Kelleher, Neil L; Isaacs, Farren J; Jewett, Michael C

    2014-06-20

    Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins enables the creation of biopolymers, proteins, and enzymes with new chemical properties, new structures, and new functions. To achieve this, amber (TAG codon) suppression has been widely applied. However, the suppression efficiency is limited due to the competition with translation termination by release factor 1 (RF1), which leads to truncated products. Recently, we constructed a genomically recoded Escherichia coli strain lacking RF1 where 13 occurrences of the amber stop codon have been reassigned to the synonymous TAA codon (rEc.E13.ΔprfA). Here, we assessed and characterized cell-free protein synthesis (CFPS) in crude S30 cell lysates derived from this strain. We observed the synthesis of 190±20 μg/mL of modified soluble superfolder green fluorescent protein (sfGFP) containing a single p-propargyloxy-L-phenylalanine (pPaF) or p-acetyl-L-phenylalanine. As compared to the parent rEc.E13 strain with RF1, this results in a modified sfGFP synthesis improvement of more than 250%. Beyond introducing a single NSAA, we further demonstrated benefits of CFPS from the RF1-deficient strains for incorporating pPaF at two- and five-sites per sfGFP protein. Finally, we compared our crude S30 extract system to the PURE translation system lacking RF1. We observed that our S30 extract based approach is more cost-effective and high yielding than the PURE translation system lacking RF1, ∼1000 times on a milligram protein produced/$ basis. Looking forward, using RF1-deficient strains for extract-based CFPS will aid in the synthesis of proteins and biopolymers with site-specifically incorporated NSAAs. PMID:24328168

  12. Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release.

    PubMed

    Zhang, Y; Oguzhan, B; Louchami, K; Chardigny, J-M; Portois, L; Carpentier, Y A; Malaisse, W J; Herchuelz, A; Sener, A

    2006-09-01

    Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+) handling, the islets from omega-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K(+) concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from omega-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca(2+) or K(+) concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca(2+), theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected omega-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats. PMID:16912059

  13. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    SciTech Connect

    Murayama, T.; Ui, M.

    1985-06-25

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased /sup 45/Ca/sup 2 +/ uptake into the cell monolayer, and (f) increased /sup 86/Rb/sup +/ uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca/sup 2 +/ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca/sup 2 +/-mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca/sup 2 +/ gating.

  14. pH-triggered sustained release of arsenic trioxide by polyacrylic acid capped mesoporous silica nanoparticles for solid tumor treatment in vitro and in vivo.

    PubMed

    Xiao, Xuecheng; Liu, Yangyang; Guo, Manman; Fei, Weidong; Zheng, Hongyue; Zhang, Rongrong; Zhang, Yan; Wei, Yinghui; Zheng, Guohua; Li, Fanzhu

    2016-07-01

    Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell in vitro or solid tumor in vivo. However, its effect on solid tumor in vivo was hampered by its poor pharmacokinetics and dose-limited toxicity. In this study, a polyacrylic acid capped pH-triggered mesoporous silica nanoparticles was conducted to improve the pharmacokinetics and enhance the antitumor effect of arsenic trioxide. The mesoporous silica nanoparticles loaded with arsenic trioxide was grafted with polyacrylic acid (PAA-ATO-MSN) as a pH-responsive biomaterial on the surface to achieve the release of drug in acidic microenvironment of tumor, instead of burst release action in circulation. The nanoparticles were characterized with uniform grain size (particle sizes of 158.6 ± 1.3 nm and pore sizes of 3.71 nm, respectively), historically comparable drug loading efficiency (11.42 ± 1.75%), pH-responsive and strengthened sustained release features. The cell toxicity of amino groups modified mesoporous silica nanoparticles (NH2-MSN) was significantly reduced by capping of polyacrylic acid. In pharmacokinetic studies, the half time (t1/2β) was prolonged by 1.3 times, and the area under curve) was increased by 2.6 times in PAA-ATO-MSN group compared with free arsenic trioxide group. Subsequently, the antitumor efficacy in vitro (SMMC-7721 cell line) and in vivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug. These results suggest that the polyacrylic acid capped mesoporous silica nanoparticles (PAA-MSN) will be a promising nanocarrier for improving pharmacokinetic features and enhancing the anti-tumor efficacy of arsenic trioxide. PMID:27059495

  15. Stomach acid test

    MedlinePlus

    Gastric acid secretion test ... of the cells in the stomach to release acid. The stomach contents are then removed and analyzed. ... 3.5). These numbers are converted to actual acid production in units of milliequivalents per hour in ...

  16. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome

    PubMed Central

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

  17. Prolonged effect of a novel S-nitrosated glyco-amino acid in endothelium-denuded rat femoral arteries: potential as a slow release nitric oxide donor drug

    PubMed Central

    Megson, I L; Greig, I R; Gray, G A; Webb, D J; Butler, A R

    1997-01-01

    The vasodilator properties of a novel S-nitrosated glyco-amino acid (RIG200) were investigated in isolated rat femoral arteries and compared with those of the parent S-nitrosothiol compound, S-nitroso-N-acetylpenicillamine (SNAP). Spectrophotometric analysis revealed that 2.5 mM solutions of RIG200 decomposed more slowly (half-life (t1/2)=216.2±26.7 min) than SNAP (t1/2=37.2±13.8 min) in Krebs buffer at 24°C. Furthermore, the rate of decomposition of SNAP, but not of RIG200, was significantly reduced by the Cu(I) chelator, neocuproine. We concluded that the relative stability of RIG200 is due, at least in part, to its resistance to trace Cu(I)-catalyzed decomposition. Nitric oxide (NO) generation from SNAP and RIG200 was confirmed by use of an NO electrode. Experiments to investigate the vasodilator effects of RIG200 were carried out on isolated femoral arteries taken from adult male Wistar rats (400–550 g). Lengths of artery (7–8 mm long) were cannulated, dissected free and perfused at constant flow rate (0.6 ml min−1) with Krebs buffer. Vessels were precontracted with phenylephrine (10.2±0.3 μM) and developed pressures of 91.8 ± 4 mmHg, detected upstream by a differential pressure transducer. Concentration-dependent vasodilator responses to bolus injections of SNAP or RIG200 (10 μl; 10−8–10−3 M) made into the perfusate of endothelium-intact vessels were transient, recovering the pre-injection pressure in <20 min. Responses to equivalent bolus injections of SNAP in endothelium-denuded vessels were also transient but those in response to concentrations of RIG200 >10−5 M were sustained. Responses to 10−3 M RIG200 were sustained for periods >4 h. Sustained vasodilatation was reversed by the NO scavenger, ferrohaemoglobin (10 μM) but was unaffected by the NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (200 μM), indicating involvement of NO from a source other than NO synthase. We suggest that a

  18. A novel feruloyl esterase from rumen microbial metagenome: Gene cloning and enzyme characterization in the release of mono- and diferulic acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A feruloyl esterase (FAE) gene was isolated from a rumen microbial metagenome, cloned into E. coli, and expressed in active form. The enzyme (RuFae4) was classified as a Type D feruloyl esterase based on its action on synthetic substrates and ability to release diferulates. The RuFae4 alone releas...

  19. INFLUENCE OF THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID ON RAT ESTROUS CYCLICITY AND OVARIAN FOLLICULAR STEROID RELEASE IN VITRO

    EPA Science Inventory

    The drinking water disinfection by-product, dibromoacetic acid (DBA) has been reported to affect gonadal functions in the male rat. However, there is little information regarding its influence on female reproductive activity. Consequently, the present study investigated the eff...

  20. Optimization (Central Composite Design) and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid) Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    PubMed Central

    Singh, Gurinder; Pai, Roopa S.

    2014-01-01

    The objective of the current study is to develop nanoparticles (NPs) drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid) (PLGA) and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD). NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm) column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4). In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs. PMID:24672337

  1. Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway.

    PubMed

    Ciccarelli, Renata; D'Alimonte, Iolanda; Santavenere, Clara; D'Auro, Mariagrazia; Ballerini, Patrizia; Nargi, Eleonora; Buccella, Silvana; Nicosia, Simonetta; Folco, Giancarlo; Caciagli, Francesco; Di Iorio, Patrizia

    2004-09-01

    Cysteinyl-leukotrienes (cys-LTs), potent mediators in inflammatory diseases, are produced by nervous tissue, but their cellular source and role in the brain are not very well known. In this report we have demonstrated that rat cultured astrocytes express the enzymes (5'-lipoxygenase and LTC(4) synthase) required for cys-LT production, and release cys-LTs in resting condition and, to a greater extent, in response to calcium ionophore A23187, 1 h combined oxygen-glucose deprivation or 2-methyl-thioATP, a selective P2Y(1)/ATP receptor agonist. MK-886, a LT synthesis inhibitor, prevented basal and evoked cys-LT release. In addition, 2-methyl-thioATP-induced cys-LT release was abolished by suramin, a P2 receptor antagonist, or by inhibitors of ATP binding cassette proteins involved in cys-LT release. We also showed that astrocytes express cys-LT(1) and not cys-LT(2) receptors. The stimulation of these receptors by LTD(4) activated the mitogen-activated protein kinase (MAPK) pathway. This effect was: (i) insensitive to inhibitors of receptor-coupled Gi protein (pertussis toxin) or tyrosine kinase receptors (genistein); (ii) abolished by MK-571, a cys-LT(1) selective receptor antagonist, or PD98059, a MAPK inhibitor; (iii) reduced by inhibitors of calcium/calmodulin-dependent kinase II (KN-93), Ca(2+)-dependent and -independent (GF102903X) or Ca(2+)-dependent (Gö6976) protein kinase C isoforms. LTD(4) also increased astrocyte proliferation and glial fibrillary acidic protein content, which are considered hallmarks of reactive astrogliosis. Both effects were counteracted by cell pretreatment with MK-571 or PD98059. Thus, cys-LTs released from astrocytes might play an autocrine role in the induction of reactive astrogliosis that, in brain injuries, contributes to the formation of a reparative glial scar. PMID:15355318

  2. Toggle release

    NASA Technical Reports Server (NTRS)

    Graves, Thomas Joseph (Inventor); Yang, Robert Alexander (Inventor); Brown, Christopher William (Inventor)

    1988-01-01

    The invention relates to a pyrotechnic actuated release mechanism which is mechanically two fault tolerant for effecting release. It is particularly well suited for releasably connecting structures to be used in the space environment or in other aerospace applications. The device comprises a fastener plate and fastener body, each attachable to either one of a pair of structures to be joined. The fastener plate and the body are fastenable by a toggle supported at one end on the fastener plate and mounted for universal pivotal movement thereon. At its other end, which is received in a central opening in the fastener body and adapted for limited pivotal movement therein, the toggle is restrained by three retractable latching pins. Each pin is individually retractable by combustion of a pyrotechnic charge. While retraction of all three pins releases the toggle, the fastener is mechanically two fault tolerant since the failure of any single or pair of the latch pins to retract results in an asymmetrical loading on the toggle and its pivotal movement to effect a release. An annular bolt is mounted on the fastener plate as a support for the socket mounting of the toggle whereby its selective axial movement provides a means for pre-loading the toggle.

  3. Linoleic acid derivative DCP-LA ameliorates stress-induced depression-related behavior by promoting cell surface 5-HT1A receptor translocation, stimulating serotonin release, and inactivating GSK-3β.

    PubMed

    Kanno, Takeshi; Tanaka, Akito; Nishizaki, Tomoyuki

    2015-04-01

    Impairment of serotonergic neurotransmission is the major factor responsible for depression and glycogen synthase kinase 3β (GSK-3β) participates in serotonergic transmission-mediated signaling networks relevant to mental illnesses. In the forced-swim test to assess depression-like behavior, the immobility time for mice with restraint stress was significantly longer than that for nonstressed control mice. Postsynaptic cell surface localization of 5-HT1A receptor, but not 5-HT2A receptor, in the hypothalamus for mice with restraint stress was significantly reduced as compared with that for control mice, which highly correlated to prolonged immobility time, i.e., depression-like behavior. The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) restored restraint stress-induced reduction of cell surface 5-HT1A receptor and improved depression-like behavior in mice with restraint stress. Moreover, DCP-LA stimulated serotonin release from hypothalamic slices and cancelled restraint stress-induced reduction of GSK-3β phosphorylation at Ser9. Taken together, the results of the present study indicate that DCP-LA could ameliorate depression-like behavior by promoting translocation of 5-HT1A receptor to the plasma membrane on postsynaptic cells, stimulating serotonin release, and inactivating GSK-3β. PMID:24788685

  4. Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

    PubMed

    Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

    2016-04-01

    The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. PMID:26740466

  5. Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid) microsphere using hard X-ray nano-tomography revealed correlation between structural parameters and drug burst release.

    PubMed

    Huang, Xiaozhou; Li, Na; Wang, Dajiang; Luo, Yuyan; Wu, Ziyu; Guo, Zhefei; Jin, Qixing; Liu, Zhuying; Huang, Yafei; Zhang, Yongming; Wu, Chuanbin

    2015-08-10

    The objective of this study was to investigate the use of transmission hard X-ray nano-computed-tomography (nano-CT) for characterization of the pore structure and drug distribution in poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating bovine serum albumin and to study the correlation between drug distribution and burst release. The PLGA microspheres were fabricated using a double-emulsion method. The results of pore structure analysis accessed with nano-CT were compared with those acquired by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface pore interconnectivity and surface protein interconnectivity were obtained using combined nano-CT and pixel analysis. The correlation between surface protein interconnectivity with the initial burst release across various tested formulations was also analyzed. The size, shape, and distribution of the pores and protein could be clearly observed in the whole microsphere using nano-CT, whereas only the sectional information was observed using SEM or CLSM. Interconnected pores and surface connected pores could be clearly distinguished in nano-CT, which enables the quantitative analysis of surface pore interconnectivity and surface protein interconnectivity. The surface protein interconnectivity in different formulations correlated well with the burst release at 5-10h. Nano-CT provided a nondestructive, high-resolution, and three-dimensional analysis method to characterize the porous microsphere. PMID:25951620

  6. Toggle release

    NASA Technical Reports Server (NTRS)

    Graves, Thomas J. (Inventor); Yang, Robert A. (Inventor); Brown, Christopher W. (Inventor)

    1989-01-01

    A pyrotechnic actuated structural release device 10 which is mechanically two fault tolerant for release. The device 10 comprises a fastener plate 11 and fastener body 12, each attachable to a different one of a pair of structures to be joined. The fastener plate 11 and body 12 are fastenable by a toggle 13 supported at one end on the fastener plate and mounted for universal pivotal movement thereon. At its other end which is received in a central opening in the fastener body 12 and adapted for limited pivotal movement therein the toggle 13 is restrained by three retractable latching pins 61 symmetrically disposed in equiangular spacing about the axis of the toggle 13 and positionable in latching engagement with an end fitting on the toggle. Each pin 61 is individually retractable by combustion of a pyrotechnic charge 77, the expanding gases of which are applied to a pressure receiving face 67 on the latch pin 61 to effect its retraction from the toggle. While retraction of all three pins 62 releases the toggle, the fastener is mechanically two fault tolerant since the failure of any single one or pair of the latch pins to retract results in an asymmetrical loading on the toggle and its pivotal movement to effect a release. An annular bolt 18 is mounted on the fastener plate 11 as a support for the socket mounting 30, 37 of the toggle whereby its selective axial movement provides a means for preloadin