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Sample records for glycyrrhetinate glycyrrhetinyl stearate

  1. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from...

  2. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use....

  3. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared...

  4. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use....

  5. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use....

  6. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from...

  7. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from...

  8. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from...

  9. 21 CFR 582.5994 - Zinc stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc stearate. 582.5994 Section 582.5994 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from...

  10. 21 CFR 182.8994 - Zinc stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Zinc stearate. 182.8994 Section 182.8994 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8994 Zinc stearate. (a) Product. Zinc stearate prepared from stearic acid free from chickedema factor. (b) Conditions of use....

  11. 21 CFR 573.280 - Feed-grade calcium stearate and sodium stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRINKING WATER OF ANIMALS Food Additive Listing § 573.280 Feed-grade calcium stearate and sodium stearate... anticaking agents in animal feeds in accordance with current good manufacturing practices....

  12. 21 CFR 573.280 - Feed-grade calcium stearate and sodium stearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRINKING WATER OF ANIMALS Food Additive Listing § 573.280 Feed-grade calcium stearate and sodium stearate... anticaking agents in animal feeds in accordance with current good manufacturing practices....

  13. 21 CFR 573.280 - Feed-grade calcium stearate and sodium stearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRINKING WATER OF ANIMALS Food Additive Listing § 573.280 Feed-grade calcium stearate and sodium stearate... anticaking agents in animal feeds in accordance with current good manufacturing practices....

  14. 21 CFR 184.1440 - Magnesium stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Magnesium stearate. 184.1440 Section 184.1440 Food... Specific Substances Affirmed as GRAS § 184.1440 Magnesium stearate. (a) Magnesium stearate (Mg(C17H34COO)2, CAS Reg. No. 557-04-0) is the magnesium salt of stearic acid. It is produced as a white precipitate...

  15. 21 CFR 184.1229 - Calcium stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium stearate. 184.1229 Section 184.1229 Food... Specific Substances Affirmed as GRAS § 184.1229 Calcium stearate. (a) Calcium stearate (Ca(C17H35COO)2, CAS Reg. No. 1529-23-0) is the calcium salt of stearic acid derived from edible sources. It is prepared...

  16. 21 CFR 184.1440 - Magnesium stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Magnesium stearate. 184.1440 Section 184.1440 Food... GRAS § 184.1440 Magnesium stearate. (a) Magnesium stearate (Mg(C17H34COO)2, CAS Reg. No. 557-04-0) is the magnesium salt of stearic acid. It is produced as a white precipitate by the addition of...

  17. 21 CFR 184.1440 - Magnesium stearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Magnesium stearate. 184.1440 Section 184.1440 Food... Specific Substances Affirmed as GRAS § 184.1440 Magnesium stearate. (a) Magnesium stearate (Mg(C17H34COO)2, CAS Reg. No. 557-04-0) is the magnesium salt of stearic acid. It is produced as a white precipitate...

  18. 21 CFR 184.1440 - Magnesium stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Magnesium stearate. 184.1440 Section 184.1440 Food... Specific Substances Affirmed as GRAS § 184.1440 Magnesium stearate. (a) Magnesium stearate (Mg(C17H34COO)2, CAS Reg. No. 557-04-0) is the magnesium salt of stearic acid. It is produced as a white precipitate...

  19. 21 CFR 184.1440 - Magnesium stearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Magnesium stearate. 184.1440 Section 184.1440 Food... Specific Substances Affirmed as GRAS § 184.1440 Magnesium stearate. (a) Magnesium stearate (Mg(C17H34COO)2, CAS Reg. No. 557-04-0) is the magnesium salt of stearic acid. It is produced as a white precipitate...

  20. 21 CFR 573.280 - Feed-grade calcium stearate and sodium stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.280 Feed-grade calcium stearate and sodium stearate... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Feed-grade calcium stearate and sodium...

  1. 21 CFR 573.280 - Feed-grade calcium stearate and sodium stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.280 Feed-grade calcium stearate and sodium stearate... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Feed-grade calcium stearate and sodium...

  2. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    PubMed

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  3. Characterization of Lithium Stearate: Processing Aid for Filled Elastomers

    SciTech Connect

    E. Eastwood; C. Densmore

    2007-02-05

    This topical report presents work completed to characterize lithium stearate so a replacement supplier could be identified. Lithium stearate from Alfa Aesar and Chemtura was obtained and characterized along with the current material from Witco. Multiple methods were used to characterize the materials including Karl Fischer, FT-IR, differential scanning calorimetry, and thermogravimetric analysis.

  4. Preparation and Physical Properties of Starch Stearates of Low to High Degree of Substitution

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch stearates of degree of substitution (DS) 0.07-2.40 were prepared by heating dry starch and vinyl stearate in the ionic liquid BMIM dca at 75 Degrees C. Starch stearate of low DS (0.07) was insoluble in water but formed a gel and absorbed over seven times its weight of water. Starch stearate...

  5. Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases.

    PubMed

    Schwarz, Stefan; Lucas, Susana Dias; Sommerwerk, Sven; Csuk, René

    2014-07-01

    The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreases; hence, a therapy using inhibitors should be of some benefit to the patients. Drugs presently used for the treatment of AD inhibit the two ACh controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase; hence, the design of selective inhibitors is called for. Glycyrrhetinic acid seems to be an interesting starting point for the development of selective inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE activator, several derivatives, altered in position C-3 and C-30, exhibited remarkable inhibition constants in micro-molar range. Furthermore, five representative compounds were subjected to three more enzyme assays (on carbonic anhydrase II, papain and the lipase from Candida antarctica) to gain information about the selectivity of the compounds in comparison to other enzymes. In addition, photometric sulforhodamine B assays using murine embryonic fibroblasts (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue, showed a BChE selective inhibition in the single-digit micro-molar range without being cytotoxic up to 30μM. In silico molecular docking studies on the active sites of AChE and BChE were performed to gain a molecular insight into the mode of action of these compounds and to explain the pronounced selectivity for BChE. PMID:24853320

  6. Synthesis and properties of phosphono-derivatives of methyl stearate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of phosphono-derivatives of methyl stearate (PhDMS) were synthesized from methyl oleate and dialkyl H-phosphonates (dialkyl-phosphites). The alkyl groups in the phosphonates were methyl, ethyl, and butyl. The reaction can be carried to 98+% completion with a radical initiator. It is possibl...

  7. Enhanced oral bioavailability of glycyrrhetinic acid via nanocrystal formulation.

    PubMed

    Lei, Yaya; Kong, Yindi; Sui, Hong; Feng, Jun; Zhu, Rongyue; Wang, Wenping

    2016-10-01

    The purpose of this study was to prepare solid nanocrystals of glycyrrhetinic acid (GA) for improved oral bioavailability. The anti-solvent precipitation-ultrasonication method followed by freeze-drying was adopted for the preparation of GA nanocrystals. The physicochemical properties, drug dissolution and pharmacokinetic of the obtained nanocrystals were investigated. GA nanocrystals showed a mean particle size of 220 nm and shaped like short rods. The analysis results from differential scanning calorimetry and X-ray powder diffraction indicated that GA remained in crystalline state despite a huge size reduction. The equilibrium solubility and dissolution rate of GA nanocrystal were significantly improved in comparison with those of the coarse GA or the physical mixture. The bioavailability of GA nanocrystals in rats was 4.3-fold higher than that of the coarse GA after oral administration. With its rapid dissolution and absorption performance, the solid nanocrystal might be a more preferable formulation for oral administration of poorly soluble GA. PMID:27206446

  8. 18β-glycyrrhetinic acid inhibits rotavirus replication in culture

    PubMed Central

    2012-01-01

    Background Glycyrrhizin (GA) and primary metabolite 18β-glycyrrhetinic acid (GRA) are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. Methods Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. Results GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. Conclusions GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway. PMID:22616823

  9. The mechanism of hydrothermal hydrolysis for glycyrrhizic acid into glycyrrhetinic acid and glycyrrhetinic acid 3-O-mono-β-D-glucuronide in subcritical water.

    PubMed

    Fan, Rui; Li, Nan; Xu, Honggao; Xiang, Jun; Wang, Lei; Gao, Yanxiang

    2016-01-01

    To improve the bioactivity and sweetness properties of glycyrrhizic acid (GL), the hydrothermal hydrolysis of GL into glycyrrhetinic acid (GA) and glycyrrhetinic acid 3-O-mono-β-D-glucuronide (GAMG) in subcritical water was investigated. The effects of temperature, time and their interaction on the conversion ratios were analyzed and the reactions were elaborated with kinetics and thermodynamics. The results showed that GL hydrothermal hydrolysis was significantly (P < 0.05) affected by reaction time and temperature, as well as their interaction, and could be fitted into first-order kinetics. The thermodynamic analysis indicated that the hydrolysis of GL was endergonic and non-spontaneous. The hydrolytic pathways were composed of complex consecutive and parallel reactions. It was concluded that subcritical water may be a potential medium for producing GAMG and GA. PMID:26213056

  10. Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

    PubMed Central

    Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

    1989-01-01

    1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

  11. Preparation of polymeric microspheres by the solvent evaporation method using sucrose stearate as a droplet stabilizer.

    PubMed

    Yüksel, N; Baykara, T

    1997-01-01

    Polymeric microspheres containing nicardipine hydrochloride (HCl) as a reference drug were prepared with the acrylic polymers Eudragit RS and L by the solvent evaporation method. Different concentrations of sucrose stearate as a droplet stabilizer were used. Sucrose stearate affected the diffusion rate of the solvent from the preliminary emulsion droplets to the outer phase for the formation of microspheres. Increasing concentrations of sucrose stearate in the formulations caused increasing porosity on the surface of the microspheres. However, a correlation between the concentrations of sucrose stearate and diameters of microspheres could not be assessed. From this point of view, during processing, applied stirring rate was important. PMID:9394253

  12. Extruded foams prepared from high amylose starch with sodium stearate to form amylose inclusion complexes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch foams were prepared from high amylose corn starch in the presence and absence of sodium stearate and PVOH to determine how the formation of amylose-sodium stearate inclusion complexes and the addition of PVOH would affect foam properties. Low extrusion temperatures were used, and X-ray diffra...

  13. Dietary Stearate Reduces Human Breast Cancer Metastasis Burden in Athymic Nude Mice

    PubMed Central

    Evans, Lynda M.; Toline, Eric C.; Desmond, Renee; Siegal, Gene P.; Hashim, Arig Ibrahim; Hardy, Robert W.

    2010-01-01

    Stearate is an 18-carbon saturated fatty acid found in many foods in the western diet, including beef and chocolate. Stearate has been shown to have anti-cancer properties during early stages of neoplastic progression. However, previous studies have not investigated the effect of dietary stearate on breast cancer metastasis. In this study, we present evidence that exogenously supplied dietary stearate dramatically reduces the size of tumors that formed from injected human breast cancer cells within the mammary fat pads of athymic nude mice by approximately 50% and partially inhibits breast cancer cell metastasis burden in the lungs in this mouse model system. This metastatic inhibition appears to be independent of primary tumor size, as stearate fed animals that had primary tumors comparable in size to littermates fed either a safflower oil enriched diet or a low fat diet had reduced lung metastasis. Also stearate fed mice sub-groups had different primary tumor sizes but no difference in metastasis. This anti-metastasis effect may be due, at least in part, to the ability of stearate to induce apoptosis in these human breast cancer cells. Overall, this study suggests the possibility of dietary manipulation with selected long-chain saturated fatty acids such as stearate as a potential adjuvant therapeutic strategy for breast cancer patients wishing to maximize the suppression of metastatic disease. PMID:19267249

  14. Dietary stearate reduces human breast cancer metastasis burden in athymic nude mice.

    PubMed

    Evans, Lynda M; Toline, Eric C; Desmond, Renee; Siegal, Gene P; Hashim, Arig Ibrahim; Hardy, Robert W

    2009-01-01

    Stearate is an 18-carbon saturated fatty acid found in many foods in the western diet, including beef and chocolate. Stearate has been shown to have anti-cancer properties during early stages of neoplastic progression. However, previous studies have not investigated the effect of dietary stearate on breast cancer metastasis. In this study, we present evidence that exogenously supplied dietary stearate dramatically reduces the size of tumors that formed from injected human breast cancer cells within the mammary fat pads of athymic nude mice by approximately 50% and partially inhibits breast cancer cell metastasis burden in the lungs in this mouse model system. This metastatic inhibition appears to be independent of primary tumor size, as stearate fed animals that had primary tumors comparable in size to littermates fed either a safflower oil enriched diet or a low fat diet had reduced lung metastasis. Also stearate fed mice sub-groups had different primary tumor sizes but no difference in metastasis. This anti-metastasis effect may be due, at least in part, to the ability of stearate to induce apoptosis in these human breast cancer cells. Overall, this study suggests the possibility of dietary manipulation with selected long-chain saturated fatty acids such as stearate as a potential adjuvant therapeutic strategy for breast cancer patients wishing to maximize the suppression of metastatic disease. PMID:19267249

  15. Antisickling activity of butyl stearate isolated from Ocimum basilicum (Lamiaceae)

    PubMed Central

    Tshilanda, Dorothée Dinangayi; Mpiana, Pius Tshimankinda; Onyamboko, Damase Nguwo Vele; Mbala, Blaise Mavinga; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha Tshibey; Bokolo, Matthieu Kokengo; Taba, Kalulu Muzele; Kasonga, Teddy Kabeya

    2014-01-01

    Objective To perform phytochemical analyses on the leaves of Ocimum basilicum L. (O. basilicum), to elucidate the structure of isolate and then perform the antisickling activity on the crude extract and on the isolate. Methods The Emmel test performed on the acidified methanolic extract of this plant was used to evaluate the antisickling activity. The structure characterization of the active compound was performed using chromatographic techniques for the separation and the spectroscopic ones for structure elucidation (1H-NMR, 13C-NMR, COSY, HMBC). Results The chemical screening on the crude extract revealed the presence of polyphenols (flavonoids, anthocyanins, leucoanthocyanins, tannins, quinones) alkaloids, saponins, triterpenoids and steroids. The obtained extract after evaporation yielded 34.50 g (11.5%) out of 300 g of powdered leaves of O. basilicum. The acidified methanolic extract and butyl stearate showed an interesting antisickling activity. Conclusions The acidified methanolic extract and butyl stearate from O. basilicum displayed a good antisickling activity. To the best of our knowledge, this is the first time to report the antisickling activity of this compound in this plant. The synthesized compound presented the same spectroscopic characteristics than the natural one and the antisickling activities of its derivatives are understudying. PMID:25182725

  16. An Aluminum Magnesium Hydroxide Stearate-based Skin Barrier Protection Cream Used for the Management of Eczematous Dermatitis

    PubMed Central

    Bhambri, Sanjay; Michaels, Brent

    2008-01-01

    Eczematous dermatoses can often be very difficult to treat. An aluminum magnesium hydroxide stearate-based cream has recently become available for clinical use. Aluminum magnesium hydroxide stearate-based cream provides an alternative option in treating these dermatoses while providing barrier protection against external allergens and irritants. This article reviews various studies evaluating aluminum magnesium hydroxide stearate-based cream. PMID:21212843

  17. Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives

    PubMed Central

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-01-01

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. PMID:21328513

  18. Final amended report on the safety assessment of Octyldodecyl Stearoyl Stearate.

    PubMed

    2005-01-01

    Octyldodecyl Stearoyl Stearate is an ester that functions as a skin-conditioning agent and viscosity-increasing agent. It is reported to be used in 105 cosmetic products at concentrations from 2% to 15%. In an isolated human skin permeation and penetration study, 0.005% of the applied dose permeated the skin, around 3% was found in the epidermis, around 1.5% was in tape stripped skin layers, and around 95% stayed in the material applied to the skin. A formulation having 20.6% Octyldodecyl Stearoyl Stearate was classified as minimally to mildly irritating in an in vitro ocular irritation assay. Several tests of products containing from 7.5% to 12.7% Octyldodecyl Stearoyl Stearate using rabbits produced minimal to mild ocular irritation. One test of 100% Octyldodecyl Stearoyl Stearate (a trade compound) and another of 10% Octyldodecyl Stearoyl Stearate in corn oil using rabbits produced no ocular irritation. Tests using rabbits demonstrated that Octyldodecyl Stearoyl Stearate at use concentrations was non- to mildly irritating to skin; only one study reported moderate irritation. Octyldodecyl Stearoyl Stearate was not mutagenic, with or without S-9 activation, in an Ames test and did not produce a significant increase in micronucleated cells in a mouse in vivo study. In clinical single-insult patch tests at use concentrations, Octyldodecyl Stearoyl Stearate was nonirritating to mildly irritating; in a cumulative irritation study, it caused mild irritation. Octyldodecyl Stearoyl Stearate was nonsensitizing in clinical tests. Because few toxicity data were available on Octyldodecyl Stearoyl Stearate, summaries of data from existing safety assessments of related ingredients (Octyl Dodecanol, Stearic Acid, and Octyl Stearate) were included. Undiluted Octyl Dodecanol was nontoxic during acute oral and dermal studies using rats and guinea pigs. Stearic Acid was nontoxic to rats during acute oral studies, but caused toxicity during subchronic studies. Rabbits treated

  19. Degradability Enhancement of Poly(Lactic Acid) by Stearate-Zn3Al LDH Nanolayers

    PubMed Central

    Eili, Mahboobeh; Shameli, Kamyar; Ibrahim, Nor Azowa; Yunus, Wan Md Zin Wan

    2012-01-01

    Recent environmental problems and societal concerns associated with the disposal of petroleum based plastics throughout the world have triggered renewed efforts to develop new biodegradable products compatible with our environment. This article describes the preparation, characterization and biodegradation study of poly(lactic acid)/layered double hydroxide (PLA/LDH) nanocomposites from PLA and stearate-Zn3Al LDH. A solution casting method was used to prepare PLA/stearate-Zn3Al LDH nanocomposites. The anionic clay Zn3Al LDH was firstly prepared by co-precipitation method from a nitrate salt solution at pH 7.0 and then modified by stearate anions through an ion exchange reaction. This modification increased the basal spacing of the synthetic clay from 8.83 Å to 40.10 Å. The morphology and properties of the prepared PLA/stearate-Zn3Al LDH nanocomposites were studied by X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), thermogravimetric analysis (TGA), tensile tests as well as biodegradation studies. From the XRD analysis and TEM observation, the stearate-Zn3Al LDH lost its ordered stacking-structure and was greatly exfoliated in the PLA matrix. Tensile test results of PLA/stearate-Zn3Al LDH nanocomposites showed that the presence of around 1.0–3.0 wt % of the stearate-Zn3Al LDH in the PLA drastically improved its elongation at break. The biodegradation studies demonstrated a significant biodegradation rate improvement of PLA in the presence of stearate-Zn3Al LDH nanolayers. This effect can be caused by the catalytic role of the stearate groups in the biodegradation mechanism leading to much faster disintegration of nanocomposites than pure PLA. PMID:22942682

  20. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Francini-Pesenti, Francesco; Battagin, Giuliana; Ragazzi, Eugenio; Fiore, Cristina

    2005-07-01

    Cortisol is involved in the distribution and deposition of fat, and its action is regulated by the activity of 11beta-hydroxysteroid dehydrogenase. Glycyrrhetinic acid, the active principle of licorice root, blocks 11beta-hydroxysteroid dehydrogenase type 1, thus reducing the availability of cortisol at the level of adipocytes. We evaluated the effect of topical application of a cream containing glycyrrhetinic acid in the thickness of fat at the level of the thigh. Eighteen healthy women (age range 20-33 years) with normal BMI were randomly allocated to treatment, at the level of the dominant thigh, with a cream containing 2.5% glycyrrhetinic acid (n=9) or with a placebo cream containing the excipients alone (n=9). Before and after 1 month of treatment both the circumference and the thickness of the superficial fat layer of the thighs (by ultrasound analysis) were measured. The circumference and the thickness of the superficial fat layer were significantly reduced in comparison to the controlateral untreated thigh and to control subjects treated with the placebo cream. No changes were observed in blood pressure, plasma renin activity, plasma aldosterone or cortisol. The effect of glycyrrhetinic acid on the thickness of subcutaneous fat was likely related to a block of 11beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells; therefore, glycyrrhetinic acid could be effectively used in the reduction of unwanted local fat accumulation. PMID:15894038

  1. Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids.

    PubMed

    Zani, F; Cuzzoni, M T; Daglia, M; Benvenuti, S; Vampa, G; Mazza, P

    1993-12-01

    The effects of Glycyrrhiza glabra L. extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids on the mutagenicity of the ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and ribose-lysine Maillard model systems were investigated by using the Salmonella/microsome reversion assay. The protocol used allowed us to detect desmutagenic and antimutagenic activity and to avoid false positive results due to toxicity. For all the compounds tested, no desmutagenic activity was observed against ethyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine; only Glycyrrhiza glabra extract showed antimutagenic activity against ethyl methanesulfonate. On using the ribose-lysine mutagenic browning mixture, the desmutagenic activities of the Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids were observed. 18 beta-Glycyrrhetinic acid was the most active compound. Glycyrrhiza glabra extract also exhibited antimutagenic activity against ribose-lysine. PMID:8302947

  2. The influence of magnesium stearate on the characteristics of mucoadhesive microspheres.

    PubMed

    Bogataj, M; Mrhar, A; Grabnar, I; Rajtman, Z; Bukovec, P; Srcic, S; Urleb, U

    2000-01-01

    Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, x-ray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential scanning calorimetry. No differences were observed in the physical state of pipemidic acid and in microsphere shape and surface between different size fractions of microspheres, prepared with different amounts of magnesium stearate. Additionally, no correlation between the physical state of the drug in different microspheres and their biopharmaceutical properties was found. PMID:10898089

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

    PubMed

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

    2015-03-01

    Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer. PMID:25584860

  4. On the mechanism of mitochondrial permeability transition induction by glycyrrhetinic acid.

    PubMed

    Fiore, Cristina; Salvi, Mauro; Palermo, Mario; Sinigaglia, Giulietta; Armanini, Decio; Toninello, Antonio

    2004-10-01

    Glycyrrhetinic acid (GE), the aglycone of glycyrrhizic acid, a triterpene glycoside which represents one of the main constituents of licorice root, induces an oxidative stress in liver mitochondria responsible for the induction of membrane permeability transition. In fact, GE, by interacting with the mitochondrial respiratory chain, generates hydrogen peroxide which in turn oxidizes critical thiol groups and endogenous pyridine nucleotides leading to the opening of the transition pore. Most likely the reactive group of GE is the carbonyl oxygen in C-11 which, by interacting mainly with a Fe/S centre of mitochondrial complex I, generates an oxygen-centered radical responsible for the pro-oxidant action. PMID:15450957

  5. Final report on the safety assessment of PEG-25 propylene glycol stearate, PEG-75 propylene glycol stearate, PEG-120 propylene glycol stearate, PEG-10 propylene glycol, PEG-8 propylene glycol cocoate, and PEG-55 propylene glycol oleate.

    PubMed

    Johnson, W

    2001-01-01

    The ingredients considered in this safety assessment are polyethylene glycol ethers of either propylene glycol itself, propylene glycol stearate, propylene glycol oleate, or propylene glycol cocoate. They function in cosmetic formulations as surfactant--cleansing agents; surfactant-solubilizing agents; surfactant--emulsifying agents; skin conditioning agents--humectant; skin-conditioning agents--emollient; and solvents. Those in current use are used in only a small number of cosmetic formulations. Some are not currently used. Polyethylene Glycol (PEG) Propylene Glycol Cocoates and PEG Propylene Glycol Oleates are produced by the esterification of polyoxyalkyl alcohols with lauric acid and oleic acid, respectively. Although there is no information available on the method of manufacture of the other polymers, information was available describing impurities, including ethylene oxide (maximum 1 ppm), 1,4-dioxane (maximum 5 ppm), polycyclic aromatic compounds (maximum 1 ppm), and heavy metals-lead, iron, cobalt, nickel, cadmium, and arsenic included (maximum 10 ppm combined). In an acute oral toxicity study, PEG-25 Propylene Glycol Stearate was not toxic. An antiperspirant product containing 2.0% PEG-25 Propylene Glycol Stearate was nonirritating to mildly irritating to the eyes of rabbits. This product was also practically nonirritating to the skin of rabbits in single-insult occlusive patch tests. In a guinea pig sensitization test, PEG-25 Propylene Glycol Stearate was classified as nonallergenic at challenge concentrations of 25% and 50% in petrolatum. PEG-25 Propylene Glycol Stearate and PEG-55 Propylene Glycol Oleate were negative in clinical patch tests. Based on the available data, it was concluded that these ingredients are safe as used (concentrations no greater than 10%) in cosmetic formulations. Based on evidence of sensitization and nephrotoxicity in burn patients treated with a PEG-based antimicrobial preparation, the ingredients included in this review

  6. Synthesis of manganese stearate for high density polyethylene (HDPE) and its biodegradation

    NASA Astrophysics Data System (ADS)

    Aras, Neny Rasnyanti M.; Arcana, I. Made

    2015-09-01

    An oxidant additive is one type of additive used for oxo-biodegradable polymers. This additive was prepared by reaction multivalent transition metals and fatty acids to accelerate the degradation process of polymers by providing a thermal treatment or irradiation with light. This study focused on the synthesis of manganese stearate as an additive for application in High Density Polyethylene (HDPE), and the influence of manganese stearate on the characteristics of HDPE including their biodegradability. Manganese stearate was synthesized by the reaction of stearic acid with sodium hydroxide, and sodium stearate formed was reacted with manganese chloride tetrahydrate to form manganese stearate with a melting point of 100-110 °C. Based on the FTIR spectrum showed absorption peak at wave number around 1560 cm-1 which is an asymmetric vibration of CO functional group that binds to the manganese. The films of oxo-biodegradable polymer were prepared by blending HDPE and manganese stearate additives at various concentrations with using the polymer melting method, followed heating at a temperature of 50°C and 70°C for 10 days. The characterizations of the oxo-biodegradable polymers were carried out by analysis the functional groups (FTIR and ATR),thermal properties (TGA), surface properties (SEM), as well as analysis of the biodegradability (the biodegradation test by using activated sludge, % weight loss). Based on COi indicate that the additive of manganese stearate is active in oxidizing polymer by heating treatment. Results of biodegradation by microorganisms from activated sludge showed that the percentage weight loss of polymers increase with the increasing incubation time and the concentration of manganese stearate in HDPE. Biodegradability of HDPE with the addition of manganese stearate and followed by heating at a higher temperature was better observed. The highest percentage weight loss was obtained at the polymer with concentration of 0.2% manganese stearate

  7. Synthesis of manganese stearate for high density polyethylene (HDPE) and its biodegradation

    SciTech Connect

    Aras, Neny Rasnyanti M. Arcana, I Made

    2015-09-30

    An oxidant additive is one type of additive used for oxo-biodegradable polymers. This additive was prepared by reaction multivalent transition metals and fatty acids to accelerate the degradation process of polymers by providing a thermal treatment or irradiation with light. This study focused on the synthesis of manganese stearate as an additive for application in High Density Polyethylene (HDPE), and the influence of manganese stearate on the characteristics of HDPE including their biodegradability. Manganese stearate was synthesized by the reaction of stearic acid with sodium hydroxide, and sodium stearate formed was reacted with manganese chloride tetrahydrate to form manganese stearate with a melting point of 100-110 °C. Based on the FTIR spectrum showed absorption peak at wave number around 1560 cm{sup −1} which is an asymmetric vibration of CO functional group that binds to the manganese. The films of oxo-biodegradable polymer were prepared by blending HDPE and manganese stearate additives at various concentrations with using the polymer melting method, followed heating at a temperature of 50°C and 70°C for 10 days. The characterizations of the oxo-biodegradable polymers were carried out by analysis the functional groups (FTIR and ATR),thermal properties (TGA), surface properties (SEM), as well as analysis of the biodegradability (the biodegradation test by using activated sludge, % weight loss). Based on COi indicate that the additive of manganese stearate is active in oxidizing polymer by heating treatment. Results of biodegradation by microorganisms from activated sludge showed that the percentage weight loss of polymers increase with the increasing incubation time and the concentration of manganese stearate in HDPE. Biodegradability of HDPE with the addition of manganese stearate and followed by heating at a higher temperature was better observed. The highest percentage weight loss was obtained at the polymer with concentration of 0.2% manganese

  8. Study of an Acid-Free Technique for the Preparation of Glycyrrhetinic Acid from Ammonium Glycyrrhizinate in Subcritical Water.

    PubMed

    Lekar, Anna V; Borisenko, Sergey N; Vetrova, Elena V; Filonova, Olga V; Maksimenko, Elena V; Borisenko, Nikolai I; Minkin, Vladimir I

    2015-11-01

    The aim of this work was to study an application of a previously developed expedient acid-free technique for the preparation of glycyrrhetinic acid from ammonium glycyrrhizinate that requires no use of acids and toxic organic solvents. Subcritical water that serves as a reactant and a solvent was used in order to obtain glycyrrhetinic acid in good yields starting from ammonium glycyrrhizinate. It has been shown that variation of only one parameter of the process (temperature) allows alteration to thecomposition of the hydrolysis products. A new method was used for the synthesis of glycyrrhetinic acid (glycyrrhizic acid aglycone) and its monoglycoside. HPLC combined with mass spectrometry and NMR spectroscopy were used to determine the quantitative and qualitative compositions of the obtained products. The method developed for the production of glycyrrhetinic acid in subcritical water is environmentally friendly and faster than conventional hydrolysis methods that use acids and-expensive and toxic organic solvents. The proposed technique has a potential for the future development of inexpensive and environmentally friendly technologies for production of new pharmaceutical plant-based substances. PMID:26749800

  9. Detailed Chemical Kinetic Reaction Mechanism for Biodiesel Components Methyl Stearate and Methyl Oleate

    SciTech Connect

    Naik, C; Westbrook, C K; Herbinet, O; Pitz, W J; Mehl, M

    2010-01-22

    New chemical kinetic reaction mechanisms are developed for two of the five major components of biodiesel fuel, methyl stearate and methyl oleate. The mechanisms are produced using existing reaction classes and rules for reaction rates, with additional reaction classes to describe other reactions unique to methyl ester species. Mechanism capabilities were examined by computing fuel/air autoignition delay times and comparing the results with more conventional hydrocarbon fuels for which experimental results are available. Additional comparisons were carried out with measured results taken from jet-stirred reactor experiments for rapeseed methyl ester fuels. In both sets of computational tests, methyl oleate was found to be slightly less reactive than methyl stearate, and an explanation of this observation is made showing that the double bond in methyl oleate inhibits certain low temperature chain branching reaction pathways important in methyl stearate. The resulting detailed chemical kinetic reaction mechanism includes more approximately 3500 chemical species and more than 17,000 chemical reactions.

  10. Inverted polymer solar cells with enhanced fill factor by inserting the potassium stearate interfacial modification layer

    NASA Astrophysics Data System (ADS)

    Li, Jiangsheng; Jiu, Tonggang; Li, Bairu; Kuang, Chaoyang; Chen, Qiushan; Ma, Sushuang; Shu, Jie; Fang, Junfeng

    2016-05-01

    A thin potassium stearate (KSt) film combined with an optimized ZnO film was introduced to improve the fill factor (FF) of highly efficient inverted polymer solar cells (PSCs). Atomic force microscopy and contact angle measurements were used to show that the introduction of KSt did not change the morphology of interlayer. On the contrary, it is beneficial for the spread of the active layer on the interlayer. The origin of enhanced FF was systematically studied by the ideal current-voltage model for a single heterojunction solar cell and electrochemical impedance spectroscopy. On the basis of the data analysis, the reduced charge recombination loss was responsible for this improved FF. At last, when KSt was replaced by sodium stearate (NaSt), the similar experiment phenomenon was observed. This indicates that inserting a metallic stearate modified layer is a promising strategy to enhance inverted PSCs performance.

  11. Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene

    PubMed Central

    Hu, Jun; Wu, Jindan

    2013-01-01

    Summary We describe herein the two-component charge-transfer (CT) interaction induced organogel formation with 18β-glycyrrhetinic acid appended pyrene (GA-pyrene, 3) as the donor, and 2,4,7-trinitrofluorenone (TNF, 4) as the acceptor. The use of TNF (4) as a versatile electron acceptor in the formation of CT gels is demonstrated through the formation of gels in a variety of solvents. Thermal stability, stoichiometry, scanning electron microscopy (SEM), optical micrographs, and circular dichroism (CD) are performed on these CT gels to investigate their thermal and assembly properties. UV–vis, fluorescence, mass spectrometric as well as variable-temperature 1H NMR experiments on these gels suggest that the CT interaction is one of the major driving forces for the formation of these organogels. PMID:24367453

  12. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.

    PubMed

    Pellati, Donatella; Fiore, Cristina; Armanini, Decio; Rassu, Mario; Bertoloni, Giulio

    2009-04-01

    Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC). PMID:19067381

  13. Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

    PubMed Central

    Cheng, Mingrong; Chen, Houxiang; Wang, Yong; Xu, Hongzhi; He, Bing; Han, Jiang; Zhang, Zhiping

    2014-01-01

    The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model. PMID:24493926

  14. Aging of magnesium stearate under high doses gamma irradiation and oxidative conditions

    NASA Astrophysics Data System (ADS)

    Lebeau, D.; Beuvier, L.; Cornaton, M.; Miserque, F.; Tabarant, M.; Esnouf, S.; Ferry, M.

    2015-05-01

    In nuclear waste packages conditioning processes, magnesium stearate is widely used because of its high lubricating properties. For safety purposes, the radiolytic degradation of these organic materials has to be better understood to be able to predict their aging in repository conditions. This study reports the radiolytic degradation of magnesium stearate, using gamma-rays at room temperature and under air. Modifications were followed using different analytical tools (XPS, ATR-FTIR, ICP-AES, ATG and mass spectrometry). It has been observed that molecules mainly formed up to 1000 kGy of gamma irradiation dose under radio-oxidation are alkanes, hydroperoxides, double bonds in the aliphatic chain, carboxylates with aliphatic chain shorter than the one of stearate and ketones. At a dose of 4000 kGy, dicarboxylic acids are observed: the formation of these molecules needs a dose of at least 1000 kGy to be created under radio-oxidation. These observations allow us to propose a non-exhaustive degradation mechanism of magnesium stearate under gamma-irradiation at room temperature and under air.

  15. Langmuir-Blodgett Films with Bilayer Alternation of Hemicyanine Dye and Cadmium Stearate

    NASA Astrophysics Data System (ADS)

    J, Y. Fang; Z, M. Sun; S, J. Xiao; Z, H. Lu; Y, Wei; P, Stroeve

    1991-11-01

    Multilayers consisting of bilayer alternation of hemicyanine dye and cadmium stearate have been prepared by the Langmuir-Blodgett technique. x-ray diffraction and optical absorption spectra are used to characterize their periodic structures and optical properties. The results show that a well ordered superlattice is produced and the hemicyanine dye is in non-aggregated formation in the alternating multilayers.

  16. Synthesis of cobalt stearate as oxidant additive for oxo-biodegradable polyethylene

    SciTech Connect

    Asriza, Ristika O.; Arcana, I Made

    2015-09-30

    Cobalt stearate is an oxidant additives that can initiate a process of degradation in high density polyethylene (HDPE). To determine the effect of cobalt stearate in HDPE, oxo-biodegradable polyethylene film was given an irradiation with UV light or heating at various temperature. After given a heating, the FTIR spectra showed a new absorption peak at wave number 1712 cm{sup −1} indicating the presence of carbonyl groups in polymers, whereas after irradiation with UV light is not visible the presence of this absorption peak. The increase concentration of cobalt stearate added in HDPE and the higher heating temperature, the intensity of the absorption peak of the carbonyl group increased. The increasing intensity of the carbonyl group absorption is caused the presence of damage in the film surface after heating, and this result is supported by analysis the surface properties of the film with using SEM. Biodegradation tests were performed on oxo-biodegradable polyethylene film which has been given heating or UV light with using activated sludge under optimal conditions the growth of microorganisms. After biodegradation, the maximum weight decreased by 23% in the oxo-biodegradable polyethylene film with a cobalt stearate concentration of 0.2% and after heating at a temperature of 75 °C for 10 days, and only 0.69% in the same film after irradiation UV light for 10 days. Based on the results above, cobalt stearate additive is more effective to initiate the oxidative degradation of HDPE when it is initiated by heating compared to irradiation with UV light.

  17. Synthesis of cobalt stearate as oxidant additive for oxo-biodegradable polyethylene

    NASA Astrophysics Data System (ADS)

    Asriza, Ristika O.; Arcana, I. Made

    2015-09-01

    Cobalt stearate is an oxidant additives that can initiate a process of degradation in high density polyethylene (HDPE). To determine the effect of cobalt stearate in HDPE, oxo-biodegradable polyethylene film was given an irradiation with UV light or heating at various temperature. After given a heating, the FTIR spectra showed a new absorption peak at wave number 1712 cm-1 indicating the presence of carbonyl groups in polymers, whereas after irradiation with UV light is not visible the presence of this absorption peak. The increase concentration of cobalt stearate added in HDPE and the higher heating temperature, the intensity of the absorption peak of the carbonyl group increased. The increasing intensity of the carbonyl group absorption is caused the presence of damage in the film surface after heating, and this result is supported by analysis the surface properties of the film with using SEM. Biodegradation tests were performed on oxo-biodegradable polyethylene film which has been given heating or UV light with using activated sludge under optimal conditions the growth of microorganisms. After biodegradation, the maximum weight decreased by 23% in the oxo-biodegradable polyethylene film with a cobalt stearate concentration of 0.2% and after heating at a temperature of 75 °C for 10 days, and only 0.69% in the same film after irradiation UV light for 10 days. Based on the results above, cobalt stearate additive is more effective to initiate the oxidative degradation of HDPE when it is initiated by heating compared to irradiation with UV light.

  18. The protective effect of 18β-Glycyrrhetinic acid against UV irradiation induced photoaging in mice.

    PubMed

    Kong, Song-Zhi; Chen, Hai-Ming; Yu, Xiu-Ting; Zhang, Xie; Feng, Xue-Xuan; Kang, Xin-Huang; Li, Wen-Jie; Huang, Na; Luo, Hui; Su, Zi-Ren

    2015-01-01

    It has been confirmed that repeated exposure of skin to ultraviolet (UV) radiation results in cutaneous oxidative stress and inflammation, which act in concert to cause premature skin aging, well known as photoaging. 18β-Glycyrrhetinic acid (GA), widely used to treat various tissue inflammations, is the main active component of licorice root, and has also been shown to possess favorable anti-oxidative property and modulating immunity function. In the present study, we investigated the potential protective effect of GA on UV-induced skin photoaging in a mouse model. During the experimental period of ten consecutive weeks, the dorsal depilated skin of mice was treated with topical GA for 2 hours prior to UV irradiation. The results showed that GA pretreatment significantly alleviated the macroscopic and histopathological damages in mice skin caused by UV. Meanwhile, the data also indicated that GA markedly up-regulated the activities of the antioxidant enzymes (SOD, GSH-Px), and increased the content of skin collagen, while obviously decreased malonaldehyde level and inhibited high expressions of matrix metalloproteinase-1 (MMP-1) and -3 (MMP-3), as well as down-regulated the expression of inflammatory cytokines such as IL-6, TNF-α and IL-10. Taken together, these findings amply demonstrate that GA observably attenuates UV-induced skin photoaging mainly by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1 and MMP-3. PMID:25498537

  19. Effect of glycyrrhetinic acid on membrane band 3 in human erythrocytes.

    PubMed

    Fiore, Cristina; Bordin, Luciana; Pellati, Donatella; Armanini, Decio; Clari, Giulio

    2008-11-01

    Glycyrrhetinic acid (GA) is a hydrolytic product of the triterpene glycoside of glycyrrhizic acid, one of the main constituents of licorice root, which has long been studied, due to its several biological and endocrine properties. In this paper, GA was tested on human erythrocytes, and GA-induced alterations were compared with those caused by diamide, a mild oxidant inducing well-characterized cell/membrane alterations, and n-ethylmaleimide (NEM), as alkylating agent. In order to verify the biochemical steps underlying the action of GA, band 3 Tyr-phosphorylation level, enzyme recruitment and band 3 clustering in cells pre-incubated with GA before diamide treatment were all examined. Results show that GA, in a dose-dependent manner, prevents both diamide and NEM-induced band 3 Tyr-phosphorylation, but not GSH decrease caused by both compounds. In addition, diamide-induced band 3 clustering and IgG binding to altered cells were also completely reversed by GA pre-treatment. Also, when membrane sensitivity toward proteolytic digestion was tested, GA-treated cells showed high resistance to proteolysis. In conclusion, in human erythrocytes, GA is proposed to strengthen membrane integrity against both oxidative and proteolytic damage. PMID:18778682

  20. Effects of Sucrose Stearate Addition on the Quality Improvement of Ready-To-Eat Samgyetang During Storage at 25℃

    PubMed Central

    2014-01-01

    The effects of sucrose stearate at various concentrations (0.1%, 0.2%, and 0.3%, w/v) on the physico-chemical characteristics of ready-to-eat (RTE) Samgyetang were investigated during storage at 25℃ for 12 mon. Over the storage duration, the addition of sucrose stearate had no significant effects on the proximate composition of Samgyetang, including meat, broth, and porridge, or the hardness and spreadability of the porridge, although it resulted in significantly higher CIE L* values for the porridge. The CIE L* values of Samgyetang porridge with added sucrose stearate increased until 9 mon, while the control decreased until 6 mon, and the values for both changed insignificantly thereafter. The breast meat of Samgyetang treated with sucrose stearate showed higher percentages of polyunsaturated fatty acid after 3 mon and lower percentages of monounsaturated fatty acid after 6 mon compared to the control (p<0.05), while no significant differences were observed with the different sucrose stearate concentrations (p>0.05). The overall sensory acceptability scores were higher at sucrose stearate concentrations of 0.2% or 0.3% after 6 mon and at 0.1% after 9 mon compared to those of the control. PMID:26761503

  1. A molecular dynamics study of CaCO3 nanoparticles in a hydrophobic solvent with a stearate co-surfactant.

    PubMed

    Bodnarchuk, Michael S; Heyes, David M; Breakspear, Angela; Chahine, Samir; Dini, Daniele

    2015-05-28

    Stearates containing overbased detergent nanoparticles (NPs) are used as acid neutralising additives in automotive and marine engine oils. Molecular dynamics (MD) simulations of the self-assembly of calcium carbonate, calcium stearate as a co-surfactant and stabilising surfactants of such NPs in a model explicit molecular hydrophobic solvent have been carried out using a methodology described first by Bodnarchuk et al. [J. Phys. Chem. C, 2014, 118, 21092]. The cores and particles as a whole become more elongated with stearate, and the surfactant molecules are more spaced out in this geometry than in their stearate-free counterparts. The rod dimensions are found to be largely independent of the surfactant type for a given amount of CaCO3. The corresponding particles without stearate were more spherical, the precise shape depending to a greater extent on the chemical architecture of the surfactant molecule. The rod-shaped stearate containing nanoparticles penetrated a model water droplet to a greater depth than the corresponding near-spherical particle, which is possibly facilitated by the dissociation of nanoparticle surfactant molecules onto the surface of the water in this process. These simulations are the first to corroborate the nanoparticle-water penetration mechanism proposed previously by experimental groups investigating the NP acid neutralisation characteristics. PMID:25939689

  2. Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

    PubMed Central

    Huang, Qing-Chun; Wang, Mao-Jie; Chen, Xiu-Min; Yu, Wan-Lin; Chu, Yong-Liang; He, Xiao-Hong; Huang, Run-Yue

    2016-01-01

    OBJECTIVES This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. METHODS The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. RESULTS The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. CONCLUSIONS The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA. PMID:26498361

  3. Glycyrrhetinic acid as inhibitor or amplifier of permeability transition in rat heart mitochondria.

    PubMed

    Battaglia, Valentina; Brunati, Anna Maria; Fiore, Cristina; Rossi, Carlo Alberto; Salvi, Mauro; Tibaldi, Elena; Palermo, Mario; Armanini, Decio; Toninello, Antonio

    2008-01-01

    Glycyrrhetinic acid (GE), a hydrolysis product of glycyrrhizic acid, one of the main constituents of licorice root, is able, depending on its concentration, to prevent or to induce the mitochondrial permeability transition (MPT) (a phenomenon related to oxidative stress) in rat heart mitochondria (RHM). In RHM, below a threshold concentration of 7.5 microM, GE prevents oxidative stress and MPT induced by supraphysiological Ca2+ concentrations. Above this concentration, GE induces oxidative stress by interacting with a Fe-S centre of Complex I, thus producing ROS, and amplifies the opening of the transition pore, once again induced by Ca2+. GE also inhibits Ca2+ transport in RHM, thereby preventing the oxidative stress induced by the cation. However, the reduced amount of Ca2+ transported in the matrix is sufficient to predispose adenine nucleotide translocase for pore opening. Comparisons between observed results and the effects of GE in rat liver mitochondria (RLM), in which the drug induces only MPT without exhibiting any protective effect, confirm that it interacts in a different way with RHM, suggesting tissue specificity for its action. The concentration dependence of the opposite effects of GE, in RHM but not RLM, is most probably due to the existence of a different, more complex, pathway by means of which GE reaches its target. It follows that high GE concentrations are necessary to stimulate the oxidative stress capable of inducing MPT, because of the above effect, which prevents the interaction of low concentrations of GE with the Fe-S centre. The reported results also explain the mechanism of apoptosis induction by GE in cardiomyocytes. PMID:17980701

  4. [Effect of magnesium stearate on the tensile strength of tablets made with the binder Prosolv SMCC 90].

    PubMed

    Muzíková, J

    2002-01-01

    The present paper evaluated the tensile strength of tablets made from the dry binder Prosolv SMCC 90 and the influence of three concentrations of the lubricant magnesium stearate on the tensile strength of tablets manufactured from this material. The results were compared with the same evaluation in Avicel PH 102. The tested concentrations of the stearate were 0.4, 0.8 and 1.2%. The tablets were compressed by three press powers (3, 3.5, and 4 kN). On the basis of obtained results it can be stated that under the same press powers Prosolv SMCC 90 alone yields stronger compacts than Avicel PH 102. From the viewpoint of decreased strength of compacts by adding magnesium stearate, the dry binder Prosolv SMCC 90 is much less sensitive than Avicel PH 102. In Avicel PH 102 a marked decrease in tensile strength was recorded with an addition of 0.4%, which was not observed with Prosolv SMCC90. A more significant decrease in the strength of compacts was shown by the substance not until a stearate concentration of 0.8%. The highest employed stearate concentration of 1.2% decreases the tensile strength of tablets made from Prosolv SMCC 90 in the press powers of 3.5 and 4 kN two times less than the tensile strength of the compacts from Avicel PH 102. PMID:11910741

  5. Development of pH sensitive polymeric nanoparticles of erythromycin stearate

    PubMed Central

    Bhadra, Sulekha; Prajapati, Atin B.; Bhadra, Dipankar

    2016-01-01

    Context: Bioavailability of conventional tablet of erythromycin stearate is low as it is unstable at acidic pH and also shows a low dissolution rate. Objective: It was proposed to protect it from the acidic condition of the stomach along with an increase in dissolution rate by formulating pH sensitive nanoparticles. Materials and Methods: The nanoparticles were prepared by the solvent evaporation technique using different quantities of Eudragit L100-55 and polyvinyl alcohol (PVA). Size reduction was achieved by high speed homogenization technique using Digital Ultra Turrax homogenizer. The formulation was optimized using 32 factorial design, keeping drug polymer ratio and surfactant concentration as independent variables. Particle size, entrapment efficiency, and drug-release (DR) were studied as dependent variables. Results: Optimized batch containing 1:0.3 erythromycin stearate: Eudragit L100-55 ratio and 1.0% PVA showed 8.24 ± 0.71% DR in pH 1.2 in 1-h and 90.38 ± 5.97% in pH 5.5 and pH 6.8 within 2-h, respectively. Discussion: The optimized batch exhibited lower release in acidic pH and faster release in higher pH compared to the marketed preparation. Conclusion: Thus the present study concludes that pH sensitive nanoparticles of erythromycin stearate increases the dissolution of the drug in intestinal pH and also protect it from acidic pH, which may help in improving the bioavailability of erythromycin. PMID:27134466

  6. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    SciTech Connect

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik; Park, Sang-Youel

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18{beta

  7. Structure and growth of stearate monolayers on calcite: First results of an in situ X-ray reflectivity study

    SciTech Connect

    Fenter, P.; Sturchio, N.C.

    1999-10-01

    The adsorption of organic molecules at mineral-fluid interfaces has a profound influence upon geochemical reaction and transport processes, yet little is known about the in situ structures or properties of organic layers at mineral-fluid interfaces. The authors describe an X-ray reflectivity study of stearate monolayers adsorbed at the calcite surface from methanolic solutions. Using these measurements the authors are able to determine important aspects of the in situ structure, bonding, adsorption, and growth mechanisms of stearate monolayers. The experimental approach demonstrated here can be applied widely in studying the interaction of organic molecules with mineral surfaces in aqueous systems.

  8. Sucrose stearate-based proniosome-derived niosomes for the nebulisable delivery of cromolyn sodium.

    PubMed

    Abd-Elbary, A; El-laithy, H M; Tadros, M I

    2008-06-01

    A Novel approach was developed for the preparation of controlled release proniosome-derived niosomes, using sucrose stearates as non-ionic biocompatible surfactants for the nebulisable delivery of cromolyn sodium. Conventional niosomes were prepared by a reverse phase evaporation method followed by the preparation of proniosomes by spraying the optimized surfactant-lipid mixture of sucrose stearate, cholesterol and stearylamine in 7:3:0.3 molar ratio onto the surface of spray dried lactose powder. Proniosome-derived niosomes were obtained by hydrating proniosomes with 0.9% saline at 50 degrees C and mixing for approximately 2 min. All vesicles were evaluated for their particle size, morphological characteristics, entrapment efficiency, in vitro drug release, nebulisation efficiency and physical stability at 2-8 degrees C. In addition, coating carrier surface with the surfactant-lipid mixture, during preparation of proniosomes, resulted in smaller, free flowing, homogenous and smooth vesicles with high drug entrapment efficiency. Compared to a standard drug solution, a successful retardation of the drug release rate was achieved with the proniosome-derived niosomes, where the t50% value of the release profile was 18.1h compared to 1.8h. Moreover, high nebulisation efficiency percentage and good physical stability were also achieved. The results are very encouraging and offer an alternative approach to minimize the problems associated with conventional niosomes like degradation, sedimentation, aggregation and fusion. PMID:18339494

  9. 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

    PubMed

    Huang, Li-Rong; Hao, Xiao-Jiang; Li, Qi-Ji; Wang, Dao-Ping; Zhang, Jian-Xin; Luo, Heng; Yang, Xiao-Sheng

    2016-04-22

    The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay. PMID:26928299

  10. Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules.

    PubMed

    Langer, Dominik; Wicher, Barbara; Szczołko, Wojciech; Gdaniec, Maria; Tykarska, Ewa

    2016-08-01

    The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds. PMID:27484379

  11. Uptake of Etoposide in CT-26 Cells of Colorectal Cancer Using Folate Targeted Dextran Stearate Polymeric Micelles

    PubMed Central

    Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi-Aliabadi, Hojjat; Firozian, Farzin

    2014-01-01

    Targeted drug delivery using folate receptors is one of the most interesting chemotherapeutic research areas over the past few years. A novel folate targeted copolymer was synthesized using dextran stearate coupled to folic acid. FT-IR and NMR spectroscopy were used to confirm successful conjugation. Micelles prepared using this copolymer were characterized for their particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using CT-26 colorectal carcinoma cell line. FT-IR and NMR spectroscopy confirmed production of folate grafted dextran stearate copolymer. Low CMC value indicates that the copolymers are suitable for preparation of stable micelles useful in parenteral dosage forms. Particle size and zeta potential of the targeted nanoparticles were 105.5 ± 2.0 nm and −21.2 mV, respectively. IC50 of etoposide loaded in folate grafted dextran stearate enhanced about 20-fold compared to the pure drug (0.49 ± 0.11 μg/mL versus 9.41 ± 0.52 μg/mL). It seems that etoposide loaded in micelles of folate grafted dextran stearate copolymer is promising in reducing drug resistance of colorectal cancer by boosting etoposide cellular uptake. PMID:24689050

  12. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.

    PubMed

    Calò, Lorenzo A; Zaghetto, Francesca; Pagnin, Elisa; Davis, Paul A; De Mozzi, Paola; Sartorato, Paola; Martire, Giuseppe; Fiore, Cristina; Armanini, Decio

    2004-04-01

    Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors. PMID:15070972

  13. Scanning Tunneling Imaging of Bio-Organic Molecules and Their Tunneling Properties: Fatty Acids, Their Derivatives and Cholesteryl Stearate

    NASA Astrophysics Data System (ADS)

    Yoshimura, Kousei; Arakawa, Hideo; Ikai, Atsushi

    1995-06-01

    Scanning tunneling microscopy imaging was applied to long-chain fatty acids, their derivatives and cholesteryl stearate in the adsorbed state at the liquid-solid interface between phenyloctane and highly oriented pyrolytic graphite. Cerotic acid, lignoceric acid, stearic acid, sodium stearate, stearoyl amide, and stearoyl anilide all produced regular arrays of dark and bright bands. Bright bands in the images of all execept the last compound were assigned as side-by-side alignment of hydrocarbon chains based on the variation of the band width between the three fatty acids. In the case of stearoyl anilide, the bright part was assigned to aromatic ring structure and the wider dark area to the hydrocarbon part.

  14. Permeability of water and oleic acid in composite films of phase separated polypropylene and cellulose stearate blends.

    PubMed

    Krasnou, Illia; Gårdebjer, Sofie; Tarasova, Elvira; Larsson, Anette; Westman, Gunnar; Krumme, Andres

    2016-11-01

    Cellulose esters with long carbon side chains (e.g. stearate) were produced via a homogenous reaction in ionic liquids. The degree of substitution was calculated to approximately 2. The melt rheology was studied for the pure cellulose esters but also combinations of the esters and polypropylene to study the processability of a blended composite material. It was shown that the compatibility between the two components was weak, which resulted in a phase-separated composite material. The morphology and permeability of water and oleic acid of the composite films were studied and it was shown that the water permeability decreased upon addition of the cellulose ester to the polymer. The permeability of oleic acid was however unchanged, which is most probable a result of high solubility in the cellulose ester rich domains of the composites. Also, the following hypothesis is stated: cellulose stearate influence the polypropylene crystallization process by decreasing the size of spherulites. PMID:27516292

  15. Determination of calcium stearate in polyolefin samples by gas chromatographic technique after performing dispersive liquid-liquid microextraction.

    PubMed

    Ranji, Ali; Ghorbani Ravandi, Mahboobeh; Farajzadeh, Mir Ali

    2008-05-01

    In this study, a gas chromatographic method is presented for the determination of calcium stearate after its conversion to stearic acid in a polymeric matrix. A solution of hydrochloric acid in 2-propanol is used as an extracting solvent of calcium stearate and its converter to stearic acid. For stearic acid preconcentration before its injection to a separation system, a recently presented extraction method, dispersive liquid-liquid microextraction, using carbon tetrachloride as an extracting solvent is used. Finally, 1 microL of the organic phase collected at the bottom of a conical test tube after centrifuging is injected into a gas chromatograph (GC) for quantification. This method has a relatively broad linear dynamic range (50 - 2000 mg/L) with a limit of detection (LOD) of 15 mg/L for stearic acid in solution. The LOD of the proposed method in a polymeric sample using 10 mg of polymer is 60 ppm as calcium stearate. Some effective parameters, such as the time and temperature of heating, the concentration of hydrochloric acid and the volume of distilled water, were studied. PMID:18469468

  16. Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

    PubMed Central

    Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

    2013-01-01

    Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (IK), the rapidly activating (IKr) and slowly activating (IKs) components of IK, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record IK (IKr, IKs) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited IK (IKr, IKs) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of IK (IKr, IKs) and HERG K+ channel. PMID:24069049

  17. A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two-step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin.

    PubMed

    Xu, Guojie; Cai, Wei; Gao, Wei; Liu, Chunsheng

    2016-10-01

    Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world-wide. However, the key UDP-dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two-step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site-directed mutagenesis revealed that Gln-352 may be important for the initial step of glucuronosylation, and His-22, Trp-370, Glu-375 and Gln-392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two-step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin. PMID:27252088

  18. One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell

    PubMed Central

    Cong, Yue; Shi, Bingyang; Lu, Yiqing; Wen, Shihui; Chung, Roger; Jin, Dayong

    2016-01-01

    Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. PMID:26902258

  19. The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils

    PubMed Central

    Cao, Donghui; Jiang, Jing; You, Lili; Jia, Zhifang; Tsukamoto, Tetsuya; Cai, Hongke; Wang, Shidong; Hou, Zhen; Suo, Yue-er; Cao, Xueyuan

    2016-01-01

    18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug. PMID:27006947

  20. The role of glycyrrhetinic acid modification on preparation and evaluation of quercetin-loaded chitosan-based self-aggregates.

    PubMed

    Du, Hongliang; Liu, Mengrui; Yang, Xiaoye; Zhai, Guangxi

    2015-12-15

    Quercetin (QC), a type of plant-based chemical, has been reported to own anticancer activity in vivo. However, the poor water solubility limits its pharmaceutical application. In this study, two kinds of QC-loaded self-aggregates based on O-carboxymethyl chitosan-cholic acid conjugates (CMCA) were developed to improve the drug bioavailability in which glycyrrhetinic acid (GA) modification was utilized in the nanocarrier fabrication (QC-GA-CMCA) or not (QC-CMCA). These self-aggregates were prepared by a modified ultrasound-dialysis method and the role of GA modification on the evaluation of QC-loaded self-aggregates was investigated. Transmission Electron Microscopy (TEM) images revealed the formation of spherical particles of both self-aggregates. Dynamic Light Scattering (DLS) analysis and UV-VIS spectroscopy showed that the QC-GA-CMCA had smaller size, narrower size distribution, higher drug loading and entrapment efficiency than corresponding QC-CMCA aggregates. QC-GA-CMCA showed more obvious sensitivity to acidic pH condition based on the zeta potential measurements at various pHs, and fastest drug release was observed at pH 5.7 for QC-CMCA while at pH 6.5 for QC-GA-CMCA. In addition, QC-GA-CMCA demonstrated enhanced cell cytotoxicity and higher cell apoptosis rate in vitro, and also higher AUC value and a prolonged residence time of drug in vivo. PMID:26319324

  1. Induction of Apoptosis and Nonsteroidal Antiinflammatory Drug-Activated Gene 1 in Pancreatic Cancer Cells By A Glycyrrhetinic Acid Derivative

    PubMed Central

    Jutooru, Indira; Chadalapaka, Gayathri; Chintharlapalli, Sudhakar; Papineni, Sabitha; Safe, Stephen

    2009-01-01

    Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic triterpenoid derived from glycyrrhetinic acid, a bioactive phytochemical in licorice, CDODA-Me inhibits growth of Panc1 and Panc28 pancreatic cancer cell lines and activates peroxisome proliferator-activated receptor γ (PPARγ)-dependent transactivation in these cells. CDODA-Me also induced p21 and p27 protein expression and downregulates cyclin D1; however, these responses were receptor-independent. CDODA-Me induced apoptosis in Panc1 and Panc28 cells, and this was accompanied by receptor-independent induction of the proapoptotic proteins early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), and activating transcription factor-3 (ATF3). Induction of NAG-1 and Egr-1 by CDODA-Me was dependent on activation of phosphatidylinositol-3-kinase (PI3-K) and/or p42 and p38 mitogen-activated protein kinase (MAPK) pathways but there were differences between Panc28 and Panc1 cells. Induction of NAG-1 in Panc28 cells was p38-MAPK- and PI3-K-dependent but Egr-1-independent, whereas induction in Panc1 cells was associated with activation of p38-MAPK, PI3-K and p42-MAPK and was only partially Egr-1-dependent. This is the first report of the induction of the proapoptotic protein NAG-1 in pancreatic cancer cells. PMID:19125423

  2. 18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation and oxidative stress.

    PubMed

    Hasan, S K; Khan, R; Ali, N; Khan, A Q; Rehman, M U; Tahir, M; Lateef, A; Nafees, S; Mehdi, S J; Rashid, S; Shahid, A; Sultana, S

    2015-06-01

    2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-β Glycyrrhetinic acid (18β-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18β-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18β-GA at two different doses (45 and 75 mg kg(-1) b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18β-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18β-GA. Our findings suggest that pretreatment with 18β-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation. PMID:25352648

  3. One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell.

    PubMed

    Cong, Yue; Shi, Bingyang; Lu, Yiqing; Wen, Shihui; Chung, Roger; Jin, Dayong

    2016-01-01

    Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. PMID:26902258

  4. Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer.

    PubMed

    Motlekar, Nusrat A; Srivenugopal, Kalkunte S; Wachtel, Mitchell S; Youan, Bi-Botti C

    2006-02-01

    Low molecular weight heparin (LMWH) is the agent of choice for anticoagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, its therapeutic use is limited due to poor oral bioavailability. The aim of this study was to investigate the oral delivery of LMWH, ardeparin formulated with 18-beta glycyrrhetinic acid (GA), as an alternative to currently used subcutaneous (sc) delivery. Drug transport through Caco-2 cell monolayers was monitored in the presence and absence of GA by scintillation counting and transepithelial electrical resistance. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. The absorption of ardeparin after oral administration in rats was measured by an anti-factor Xa assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. Higher ardeparin permeability (~7-fold) compared to control was observed in the presence of 0.02 % GA. Regional permeability studies indicated predominant absorption in the duodenal segment. Cell viability studies showed no significant cytotoxicity below 0.01 % GA. Ardeparin oral bioavailability was significantly increased (F(relative)/(S.C). = 13.3%) without causing any damage to the intestinal tissues. GA enhanced the oral absorption of ardeparin both in vitro and in vivo. The oral formulation of ardeparin with GA could be absorbed in the intestine. These results suggest that GA may be used as an absorption enhancer for the oral delivery of LMWH. PMID:17710191

  5. 18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination.

    PubMed

    Zhou, Jieru; Cai, Wei; Jin, Min; Xu, Jingwei; Wang, Yanan; Xiao, Yichuan; Hao, Li; Wang, Bei; Zhang, Yanyun; Han, Jie; Huang, Rui

    2015-01-01

    Microglia are intrinsic immune cells in the central nervous system (CNS). The under controlled microglia activation plays important roles in inflammatory demyelination diseases, such as multiple sclerosis (MS). However, the means to modulate microglia activation as a therapeutic modality and the underlying mechanisms remain elusive. Here we show that administration of 18β-glycyrrhetinic acid (GRA), by using both preventive and therapeutic treatment protocols, significantly suppresses disease severity of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The treatment effect of GRA on EAE is attributed to its regulatory effect on microglia. GRA-modulated microglia significantly decreased pro-inflammatory profile in the CNS through suppression of MAPK signal pathway. The ameliorated CNS pro-inflammatory profile prevented the recruitment of encephalitogenic T cells into the CNS, which alleviated inflammation-induced demyelination. In addition, GRA treatment promoted remyelination in the CNS of EAE mice. The induced remyelination can be mediated by the overcome of inflammation-induced blockade of brain-derived neurotrophic factor expression in microglia, as well as enhancing oligodendrocyte precursor cell proliferation. Collectively, our results demonstrate that GRA-modulated microglia suppresses EAE through inhibiting microglia activation-mediated CNS inflammation, and promoting neuroprotective effect of microglia, which represents a potential therapeutic strategy for MS and maybe other neuroinflammatory diseases associated with microglia activation. PMID:26329786

  6. Delay effect of magnesium stearate on tablet dissolution in acidic medium.

    PubMed

    Ariyasu, Aoi; Hattori, Yusuke; Otsuka, Makoto

    2016-09-25

    Magnesium stearate (Mg-St) is a common lubricant used for solid pharmaceutical formulations and is known for its property to cause delay of tablet dissolution. In this study, the mechanism underlying the delay caused by Mg-St was investigated with model metformin hydrochloride (HCl) tablets containing Mg-St by using the stationary disk method, scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDS), and Fourier transform infrared spectroscopy (FTIR). The results revealed the process and mechanism of delay: the exposed amount of Mg-St on the tablet surface increases during the dissolution process, and tablet dissolution is limited by the diffusion of Mg-St. In addition, in the case of dissolution in acidic medium, stearic acid derived from Mg-St was detected on the tablet surface by FTIR. Because the solubility of stearic acid is lower than that of Mg-St, the slower dissolution in acidic medium than in neutral medium may be attributed to the generation of stearic acid. PMID:27444551

  7. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

    PubMed Central

    Di Pierro, Francesco; Gatti, Mario; Rapacioli, Giuliana; Ivaldi, Leandro

    2013-01-01

    Background The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31) were treated with pantoprazole and a formula (Mirgeal®) containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32) were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10). Side effects, tolerability, and compliance were also assessed. Results Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B) completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the two groups. Conclusion Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening

  8. Chromolithic method development, validation and system suitability analysis of ultra-sound assisted extraction of glycyrrhizic acid and glycyrrhetinic acid from Glycyrrhiza glabra.

    PubMed

    Gupta, Suphla; Sharma, Rajni; Pandotra, Pankaj; Jaglan, Sundeep; Gupta, Ajai Prakash

    2012-08-01

    An ultrasound-assisted extraction and chromolithic LC method was developed for simultaneous determination of glycyrrhizic acid (GA) and glycyrrhetinic acid (GL) from the root extract of Glycyrrhizza glabra using RPLC-PDA. The developed method was validated according to the International Conference on Harmonisation. The method exhibited good linearity (r2 > 0.9989) with high precision and achieved good accuracies between 97.5 to 101.3% of quantitative results. The method is more sensitive and faster (resolved within ten minutes) than the earlier developed methods using normal LC columns. PMID:22978213

  9. Growth inhibition of Mycobacterium tuberculosis by polyoxyethylene stearate present in the BACTEC pyrazinamide susceptibility test.

    PubMed

    Miller, M A; Thibert, L; Desjardins, F; Siddiqi, S H; Dascal, A

    1996-01-01

    We have previously found that approximately 3.5% of 428 clinical isolates of Mycobacterium tuberculosis yield uninterpretable results in the BACTEC pyrazinamide (PZA) susceptibility test system, because of inadequate growth. We tested the hypothesis that polyoxyethylene stearate (POES), the ingredient of the reconstituting fluid for the test, was the cause of this growth inhibition. A total of 15 isolates known for their previously uninterpretable results and 100 randomly chosen clinical isolates were tested in parallel both with and without POES. Repeat testing of the isolates with previously uninterpretable results yielded results in the presence of POES in only seven (47%). In the absence of POES, all gave interpretable results but one such result showed false resistance. For the other 100 clinical isolates, interpretable results were obtained with and without POES, but growth was enhanced in the absence of POES, especially in the PZA-susceptible strains. This was evidenced by a decreased time to attain a growth index of 200 in the control vial (4.9 days without POES versus 5.8 days with POES; P < 0.001) and a higher mean growth index ratio on the day of interpretation of the test (7.4% without POES versus 2.2% with POES; P < 0.001). However, the enhanced growth without POES led to 20 susceptible strains being misinterpreted as either resistant or borderline. We suggest that isolates of M. tuberculosis which yield uninterpretable results in the BACTEC PZA test system should be retested both with and without POES. If interpretable results indicating PZA resistance are obtained only in the absence of POES, the result should be confirmed by a pyrazinamidase assay or by the conventional proportion method. Routine omission of POES from the BACTEC test for all clinical strains is discouraged because of the unacceptably high false-resistance rates. PMID:8748279

  10. Vegetable-derived magnesium stearate functionality evaluation by DM(3) approach.

    PubMed

    Haware, Rahul V; Dave, Vivek S; Kakarala, Bhavyasri; Delaney, Sean; Staton, Scott; Munson, Eric; Gupta, Mali Ram; Stagner, William C

    2016-06-30

    This study quantifies the lubricating efficiency of two grades of crystalline vegetable-derived magnesium stearate (MgSt-V) using the DM(3) approach, which utilizes design of experiments (D) and multivariate analysis techniques (M3) to evaluate the effect of a material's (M1) molecular and macroscopic properties and manufacturing factors (M2) on critical product attributes. A 2(3) factorial design (2 continuous variables plus 1 categorical factor) with three center points for each categorical factor was used to evaluate the effect of MgSt-V fraction and blend time on running powder basic flow energy (BFE), tablet mechanical strength (TMS), disintegration time (DT), and running powder lubricant sensitivity ratio (LSR). Molecular characterization of MgSt-V employed moisture sorption-desorption analysis, (13)C nuclear magnetic resonance spectroscopy, thermal analysis, and powder X-ray diffraction. MgSt-V macroscopic analysis included mean particle size, specific surface area, particle morphology, and BFE. Principal component analysis and partial least squares multivariate analysis techniques were used to develop predictive qualitative and quantitative relationships between the molecular and macroscopic properties of MgSt-V grades, design variables, and resulting tablet formulation properties. MgSt-V fraction and blending time and their square effects showed statistical significant effects. Significant variation in the molecular and macroscopic properties of MgSt-V did not have a statistically significant impact on the studied product quality attributes (BFE, TMS, DT, and LSR). In setting excipient release specifications, functional testing may be appropriate in certain cases to assess the effect of statistically significant different molecular and macroscopic properties on product quality attributes. PMID:27108117

  11. Semi-solid Sucrose Stearate-Based Emulsions as Dermal Drug Delivery Systems

    PubMed Central

    Klang, Victoria; Schwarz, Julia C.; Matsko, Nadejda; Rezvani, Elham; El-Hagin, Nivine; Wirth, Michael; Valenta, Claudia

    2011-01-01

    Mild non-ionic sucrose ester surfactants can be employed to produce lipid-based drug delivery systems for dermal application. Moreover, sucrose esters of intermediate lipophilicity such as sucrose stearate S-970 possess a peculiar rheological behavior which can be employed to create highly viscous semi-solid formulations without any further additives. Interestingly, it was possible to develop both viscous macroemulsions and fluid nanoemulsions with the same chemical composition merely by slight alteration of the production process. Optical light microscopy and cryo transmission electron microscopy (TEM) revealed that the sucrose ester led to the formation of an astonishing hydrophilic network at a concentration of only 5% w/w in the macroemulsion system. A small number of more finely structured aggregates composed of surplus surfactant were likewise detected in the nanoemulsions. These discoveries offer interesting possibilities to adapt the low viscosity of fluid O/W nanoemulsions for a more convenient application. Moreover, a simple and rapid production method for skin-friendly creamy O/W emulsions with excellent visual long-term stability is presented. It could be shown by franz-cell diffusion studies and in vitro tape stripping that the microviscosity within the semi-solid formulations was apparently not influenced by their increased macroviscosity: the release of three model drugs was not impaired by the complex network-like internal structure of the macroemulsions. These results indicate that the developed semi-solid emulsions with advantageous application properties are highly suitable for the unhindered delivery of lipophilic drugs despite their comparatively large particle size and high viscosity. PMID:24310496

  12. Structural basis for 18-β-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor

    PubMed Central

    Zhang, Hong; Huang, Qiang; Zhai, Jing; Zhao, Yi-ning; Zhang, Li-ping; Chen, Yun-yun; Zhang, Ren-wei; Li, Qing; Hu, Xiao-peng

    2015-01-01

    Aim: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Methods: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-β-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. Results: A natural compound 18-β-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 μmol/L and 0.93 μmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 μmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the γ-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. Conclusion: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors. PMID:26279158

  13. Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

    PubMed Central

    Li, Jingjing; Chen, Tong; Deng, Feng; Wan, Jingyuan; Tang, Yalan; Yuan, Pei; Zhang, Liangke

    2015-01-01

    We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity. PMID:26346750

  14. 18β-Glycyrrhetinic acid suppresses cell proliferation through inhibiting thromboxane synthase in non-small cell lung cancer.

    PubMed

    Huang, Run-Yue; Chu, Yong-Liang; Huang, Qing-Chun; Chen, Xiu-Min; Jiang, Ze-Bo; Zhang, Xian; Zeng, Xing

    2014-01-01

    18β-Glycyrrhetinic acid (18β-GA) is a bioactive component of licorice. The anti-cancer activity of 18β-GA has been studied in many cancer types, whereas its effects in lung cancer remain largely unknown. We first showed that 18β-GA effectively suppressed cell proliferation and inhibited expression as well as activity of thromboxane synthase (TxAS) in non-small cell lung cancer (NSCLC) cells A549 and NCI-H460. In addition, the administration of 18β-GA did not have any additional inhibitory effect on the decrease of cell proliferation induced by transfection with TxAS small interference RNA (siRNA). Moreover, 18β-GA failed to inhibit cell proliferation in the immortalized human bronchial epithelial cells 16HBE-T and another NSCLC cell line NCI-H23, both of which expressed minimal level of TxAS as compared to A549 and NCI-H460. However, 18β-GA abolished the enhancement of cell proliferation induced by transfection of NCI-H23 with pCMV6-TxAS plasmid. Further study found that the activation of both extracellular signal-regulated kinase (ERK)1/2 and cyclic adenosine monophosphate response element binding protein (CREB) induced by TxAS cDNA transfection could be totally blocked by 18β-GA. Altogether, we have delineated that, through inhibiting TxAS and its initiated ERK/CREB signaling, 18β-GA suppresses NSCLC cell proliferation. Our study has highlighted the significance of 18β-GA with respect to prevention and treatment of NSCLC. PMID:24695790

  15. In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4

    PubMed Central

    Lv, Qiao-Li; Wang, Gui-Hua; Chen, Shu-Hui; Hu, Lei; Zhang, Xue; Ying, Guo; Qin, Chong-Zhen; Zhou, Hong-Hao

    2015-01-01

    Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in human liver microsomes (HLMs) and recombinant cDNA-expressed enzyme systems using a HPLC-MS/MS CYP-specific probe substrate assay. With midazolam as the probe substrate, GA greatly decreased CYP3A4 activity with IC50 values of 8.195 μM in HLMs and 7.498 μM in the recombinant cDNA-expressed CYP3A4 enzyme system, respectively. It significantly decreased CYP3A4 activity in a dose- but not time-dependent manner. Results from Lineweaver–Burk plots showed that GA could inhibit CYP3A4 activity competitively, with a Ki value of 1.57 μM in HLMs. Moreover, CYP2C9 and CYP2C19 could also be inhibited significantly by GA with IC50 of 42.89 and 40.26 μM in HLMs, respectively. Other CYP450 isoforms were not markedly affected by GA. The inhibition was also confirmed by an in vivo study of mice. In addition, it was observed that mRNA expressions of the Cyps2c and 3a family decreased significantly in the livers of mice treated with GA. In conclusion, this study indicates that GA may exert herb-drug interactions by competitively inhibiting CYP3A4. PMID:26712778

  16. Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

    PubMed Central

    Cheng, Mingrong; Xu, Hongzhi; Wang, Yong; Chen, Houxiang; He, Bing; Gao, Xiaoyan; Li, Yingchun; Han, Jiang; Zhang, Zhiping

    2013-01-01

    Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma. PMID:24187487

  17. Increasing the stearate content in seed oil of Brassica juncea by heterologous expression of MlFatB affects lipid content and germination frequency of transgenic seeds.

    PubMed

    Bhattacharya, Surajit; Sinha, Saheli; Das, Natasha; Maiti, Mrinal K

    2015-11-01

    Fatty acids from dietary lipids can impart both beneficial and harmful health effects. The compositional balance between saturated and unsaturated fatty acids plays a decisive role in maintaining the physiological harmony, proper growth and development in the human system. In case of Brassica juncea seed oil, the level of saturated fatty acid, especially desirable stearate is very much lower than the recommended value, along with a high content of nutritionally undesirable erucic acid. Therefore, in order to shift the carbon flux towards the production of stearate at the expense of erucate, the MlFatB gene encoding a FatB thioesterase from Madhuca longifolia (latifolia) was expressed heterologously in seed tissues of B. juncea. The functional MlFatB competed with the highly active endogenous BjFatA thioesterase, and the transgenic B. juncea lines showed noteworthy changes in their seed fatty acid profiles. The proportion of stearate increased up to 16-fold, constituting almost 31% of the total fatty acids along with the production of arachidic acid in significant amount (up to ∼11%). Moreover, the content of erucate was reduced up to 71% in the seed oils of transgenic lines. Although a nutritionally desirable fatty acid profile was achieved, the transgenic seeds exhibit reduction or abolition of seed germination in addition to a decrease in seed lipid content. The findings of the present study revealing the stearoyl-ACP thioesterase-mediated enhancement of the stearate content that is associated with reduced germination frequency of transgenic B. juncea seeds, may explain why no natural or induced stearate-rich Brassica has been found or developed. Furthermore, this study also suggests that the newly characterized MlFatB is a potential candidate gene for refined metabolic engineering strategy in B. juncea or other plant species for increasing stearate content in seed oil. PMID:26351151

  18. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer

    PubMed Central

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul

    2015-01-01

    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

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

    PubMed

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

    2016-06-01

    In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics. PMID:26556526

  20. Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy.

    PubMed

    Yan, Tingsheng; Li, Dalong; Li, Jiwei; Cheng, Feng; Cheng, Jinju; Huang, Yudong; He, Jinmei

    2016-09-01

    A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro. In simulated body fluid with 10mM glutathione, the release rate in 12h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy. PMID:27281238

  1. Impact of drying on solid state modifications and drug distribution in ibuprofen-loaded calcium stearate pellets.

    PubMed

    Schrank, S; Kann, B; Saurugger, E; Ehmann, H; Werzer, O; Windbergs, M; Glasser, B J; Zimmer, A; Khinast, J; Roblegg, E

    2014-02-01

    Drying is a common pharmaceutical process, whose potential to alter the final drug properties-even at relatively low temperatures-is often neglected. The present study addresses the impact of drying at 20 and 50 °C on wet-extruded calcium stearate (CaSt) pellets. Drying at 20 °C caused the majority of ibuprofen to accumulate at the pellet surface due to a strong convective flow from the pellet's center to the surface. In contrast, pellets dried at 50 °C still contained ibuprofen in the pellet's interior due to the higher drying rate and the associated film breakage during drying. Moreover, the higher drying temperature caused CaSt to form a second lamellar phase and ibuprofen to convert (partly) into its amorphous state. Overall, the drying process affected the solid state and the spatial ibuprofen distribution within the pellet. Knowledge of these effects can aid in tailoring advanced multipellet formulations. PMID:24400735

  2. Influence of two different alcohols in the esterification of fatty acids over layered zinc stearate/palmitate.

    PubMed

    de Paiva, Eduardo José Mendes; Corazza, Marcos Lúcio; Sierakowski, Maria Rita; Wärnå, Johan; Murzin, Dmitry Yu; Wypych, Fernando; Salmi, Tapio

    2015-10-01

    In this work, esterification of fatty acids (oleic, linoleic and stearic acid) with a commercial zinc carboxylate (a layered compound formed by simultaneous intercalation of stearate and palmitate anions) was performed. Kinetic modeling using a quasi-homogeneous approach successfully fitted experimental data at different molar ratio of fatty acids/alcohols (1-butanol and 1-hexanol) and temperature. An apparent first-order reaction related to all reactants was found and activation energy of 66 kJ/mol was reported. The catalyst showed to be unique, as it can be easily recovered like a heterogeneous catalysts behaving like ionic liquids. In addition, this catalyst demonstrated a peculiar behavior, because higher reactivity was observed with the increase in the alcohols chain length compared to the authors' previous work using ethanol. PMID:26143001

  3. Synergistic effect of combination of Irganox 1010 and zinc stearate on thermal stabilization of electron beam irradiated HDPE/EVA both in hot water and oven

    NASA Astrophysics Data System (ADS)

    Hassanpour, S.; Khoylou, F.

    2007-11-01

    Thermo-oxidative stability of HDPE/EVA blends can be considerably increased by combination of a high-molecular weight phenolic antioxidant and zinc stearate. In this work, the post-irradiation thermal stability of HDPE/EVA blends has been studied. High-density polyethylene and its blends with ethylene-vinylacetate copolymer in both pure form and mixed with Irganox 1010 and zinc stearate were exposed to electron beam radiation at doses between 80 and 150 kGy, at room temperature, in air. In order to evaluate the thermal stability of the samples, post-irradiation heat treatments were done in both hot water bath at 95 °C and in an oven at 140 °C. The mechanical properties and changes in the chemical structure were determined during thermal aging in hot water and oven. The gel content was enhanced by increasing EVA concentration in all applied doses. The stabilized blends have lower gel content than the unstabilized samples. From the results of heat aging treatments it was observed that the thermal stability of the unstabilized blend samples was lower than HDPE. Thermal stability of the samples has been improved by incorporation of Irganox 1010 and zinc stearate. Formation of hydroxyl group was insignificant for stabilized samples during heat aging in both conditions. Also, the changes in the value of oxidation induction time (OIT) for the stabilized samples were negligible after prolonged immersion in hot water.

  4. Effect of surface coating with magnesium stearate via mechanical dry powder coating approach on the aerosol performance of micronized drug powders from dry powder inhalers.

    PubMed

    Zhou, Qi Tony; Qu, Li; Gengenbach, Thomas; Larson, Ian; Stewart, Peter J; Morton, David A V

    2013-03-01

    The objective of this study was to investigate the effect of particle surface coating with magnesium stearate on the aerosolization of dry powder inhaler formulations. Micronized salbutamol sulphate as a model drug was dry coated with magnesium stearate using a mechanofusion technique. The coating quality was characterized by X-ray photoelectron spectroscopy. Powder bulk and flow properties were assessed by bulk densities and shear cell measurements. The aerosol performance was studied by laser diffraction and supported by a twin-stage impinger. High degrees of coating coverage were achieved after mechanofusion, as measured by X-ray photoelectron spectroscopy. Concomitant significant increases occurred in powder bulk densities and in aerosol performance after coating. The apparent optimum performance corresponded with using 2% w/w magnesium stearate. In contrast, traditional blending resulted in no significant changes in either bulk or aerosolization behaviour compared to the untreated sample. It is believed that conventional low-shear blending provides insufficient energy levels to expose host micronized particle surfaces from agglomerates and to distribute guest coating material effectively for coating. A simple ultra-high-shear mechanical dry powder coating step was shown as highly effective in producing ultra-thin coatings on micronized powders and to substantially improve the powder aerosolization efficiency. PMID:23196863

  5. Inhibitory effects of polyoxyethylene stearate, PANTA, and neutral pH on growth of Mycobacterium genavense in BACTEC primary cultures.

    PubMed

    Realini, L; Van Der Stuyft, P; De Ridder, K; Hirschel, B; Portaels, F

    1997-11-01

    We report on the influences of polyoxyethylene stearate (POES), PANTA, and pH on primary cultures of Mycobacterium genavense in BACTEC vials. As a model for primary cultures from tissue, seven different strains first isolated from AIDS patients (five from Switzerland and two from the United States) were inoculated into nude mice in order to obtain large amounts of bacilli to test different conditions simultaneously. Our results demonstrate that the size of the inoculum (10[6] acid-fast bacilli/vial), an acid pH (pH 6.0), and the absence of additives (POES and PANTA) significantly (P < 0.001) increased the probability of a successful culture in 1 month, considering growth index (GI) of > or =100 or a GI of > or =999 as criterion of success. In logistic regression analysis, all factors maintained a significant (P < 0.001) independent effect, and no interactions were observed between them. The best conditions for the primary cultures of M. genavense were the use of Middlebrook 7H12 medium at pH 6.0 without any additives. PMID:9350735

  6. Real-time monitoring of lubrication properties of magnesium stearate using NIR spectrometer and thermal effusivity sensor.

    PubMed

    Nakagawa, Hiroshi; Kano, Manabu; Hasebe, Shinji; Suzuki, Tatsuya; Wakiyama, Naoki

    2013-01-30

    Real-time monitoring techniques based on an NIR spectrometer and a thermal effusivity sensor for lubrication properties of magnesium stearate (Mg-St) are proposed. The lubrication properties of Mg-St are defined by its concentration distribution and flatting state in a mixture. The concentration distribution of Mg-St significantly affects the absorbance in the NIR wavelength region between 1128 nm and 1240 nm. Thus, the absorbance area in this region after baseline correction was selected as a monitoring index (MI). In laboratory-scale experiments, the difference of Mg-St concentration distribution could be detected by the proposed MI with high sensitivity. In addition, experimental results using spherical mannitol granules confirmed that the changes of the flatting state of Mg-St could also be detected by the proposed MI. Similar experiments with spherical mannitol granules and the thermal effusivity sensor confirmed that effusivity could also be used to detect the changes of the flatting state of Mg-St. The applicability of these monitoring techniques was verified using a 2000 L commercial-scale blender equipped with the NIR spectrometer and the thermal effusivity sensor. The results showed that both lubrication properties could be monitored by the proposed MI, and that the flatting state of Mg-St could be monitored more sensitively by using the effusivity. PMID:23174413

  7. Alginate gel-coated oil-entrapped alginate-tamarind gum-magnesium stearate buoyant beads of risperidone.

    PubMed

    Bera, Hriday; Boddupalli, Shashank; Nandikonda, Sridhar; Kumar, Sanoj; Nayak, Amit Kumar

    2015-01-01

    A novel alginate gel-coated oil-entrapped calcium-alginate-tamarind gum (TG)-magnesium stearate (MS) composite floating beads was developed for intragastric risperidone delivery with a view to improving its oral bioavailability. The TG-blended alginate core beads containing olive oil and MS as low-density materials were accomplished by ionotropic gelation technique. Effects of polymer-blend ratio (sodium alginate:TG) and crosslinker (CaCl2) concentration on drug entrapment efficiency (DEE, %) and cumulative drug release after 8 h (Q8h, %) were studied to optimize the core beads by a 3(2) factorial design. The optimized beads (F-O) exhibited DEE of 75.19±0.75% and Q8h of 78.04±0.38% with minimum errors in prediction. The alginate gel-coated optimized beads displayed superior buoyancy and sustained drug release property. The drug release profiles of the drug-loaded uncoated and coated beads were best fitted in Higuchi kinetic model with Fickian and anomalous diffusion driven mechanisms, respectively. The optimized beads yielded a notable sustained drug release profile as compared to marketed immediate release preparation. The uncoated and coated Ca-alginate-TG-MS beads were also characterized by SEM, FTIR and P-XRD analyses. Thus, the newly developed alginate-gel coated oil-entrapped alginate-TG-MS composite beads are suitable for intragastric delivery of risperidone over a prolonged period of time. PMID:25861741

  8. The licorice pentacyclic triterpenoid component 18β-glycyrrhetinic acid enhances the activity of antibiotics against strains of methicillin-resistant Staphylococcus aureus.

    PubMed

    de Breij, A; Karnaoukh, T G; Schrumpf, J; Hiemstra, P S; Nibbering, P H; van Dissel, J T; de Visser, P C

    2016-04-01

    This study aimed to identify compounds that enhance the activity of current antibiotics against multidrug-resistant bacteria. Screening of a 350+ compound proprietary small molecules library revealed that the Glycyrrhiza glabra (licorice)-derived triterpenoid 18β-glycyrrhetinic acid (18β-GA) potentiated the antibacterial activity of certain antibiotics against Staphylococcus aureus. Here, we evaluated the ability of pentacyclic triterpenoids to potentiate the activity of antibiotics against strains of methicillin-resistant S. aureus (MRSA). Checkerboard assays were used to assess the minimum inhibitory concentration (MIC) of tobramycin and ten pentacyclic triterpenoids against S. aureus. The effect of 18β-GA on the MIC of different antibiotics against MRSA was also determined in an in vitro airway MRSA infection model. 18β-GA enhanced the bactericidal activity of the aminoglycosides tobramycin, gentamicin and amikacin, and of polymyxin B against two MRSA strains, reducing the MIC of these antibiotics 32-64-fold [fractional inhibitory concentration index (FICI) of 0.12-0.13]. Other β-amyrin triterpenoids and α-amyrin triterpenoids did not exert such synergistic effects. 18β-GA did not enhance the activity of antibiotics from other structural classes against the MRSA strains. In an air-exposed airway epithelial cell culture, 18β-GA enhanced the bactericidal activity of tobramycin and polymyxin B against the MRSA strain. These data demonstrate the potential of 18β-GA to synergise with certain types of antibiotics to eliminate strains of MRSA. PMID:26780691

  9. The Protective Effects of Isoliquiritigenin and Glycyrrhetinic Acid against Triptolide-Induced Oxidative Stress in HepG2 Cells Involve Nrf2 Activation

    PubMed Central

    Cao, Ling-Juan; Li, Huan-De; Yan, Miao; Li, Zhi-Hua; Gong, Hui; Jiang, Pei; Deng, Yang; Fang, Ping-Fei; Zhang, Bi-Kui

    2016-01-01

    Triptolide (TP), an active ingredient of Tripterygium wilfordii Hook f., possesses a wide range of biological activities. Oxidative stress likely plays a role in TP-induced hepatotoxicity. Isoliquiritigenin (ISL) and glycyrrhetinic acid (GA) are potent hepatoprotection agents. The aim of the present study was to investigate whether Nrf2 pathway is associated with the protective effects of ISL and GA against TP-induced oxidative stress or not. HepG2 cells were treated with TP (50 nM) for 24 h after pretreatment with ISL and GA (5, 10, and 20 μM) for 12 h and 24 h, respectively. The results demonstrated that TP treatment significantly increased ROS levels and decreased GSH levels. Both ISL and GA pretreatment decreased ROS and meanwhile enhanced intracellular GSH content. Additionally, TP treatment obviously decreased the protein expression of Nrf2 and its target genes including HO-1 and MRP2 except NQO1. Moreover, both ISL and GA displayed activities as inducers of Nrf2 and increased the expression of HO-1, NQO1, and MRP2. Taken together the current data confirmed that ISL and GA could activate the Nrf2 antioxidant response in HepG2 cells, increasing the expression of its target genes which may be partly associated with their protective effects in TP-induced oxidative stress. PMID:26904149

  10. Chemopreventive effect of 18β-glycyrrhetinic acid via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2).

    PubMed

    Hasan, Syed Kazim; Siddiqi, Aisha; Nafees, Sana; Ali, Nemat; Rashid, Summya; Ali, Rashid; Shahid, Ayaz; Sultana, Sarwat

    2016-05-01

    Hepatocellular carcinoma is one of the most common lethal diseases worldwide and there is no effective treatment till date. Natural products derived from the plants play an important role in chemoprevention and act as therapeutic antitumor agents. Licorice is a plant that has been used in food and medicine for the treatment of various diseases. 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid obtained from the roots of licorice plant, is reported to possess various pharmacological properties such as antitumor and antiinflammatory activities. The present study was designed to elucidate the chemopreventive effect of 18β-GA through antiinflammation, antiproliferation, and induction of apoptosis in human hepatoma cell line HepG2. 18β-GA significantly inhibits the proliferation of HepG2 cell without affecting the normal liver cell line (Chang's). In the present study, 18β-GA increased the formation of reactive oxygen species, nitric oxide production, and loss of mitochondrial membrane potential, suggesting the involvement of 18β-GA in apoptosis which was also confirmed by assessing the markers involved in apoptosis like caspase-3, caspase-9, Bax:Bcl-2 ratio, and cleaved PARP. 18β-GA also downregulated the expression of inflammatory proteins such as NF-κB, iNOS, and COX-2. Keeping these data into consideration, our results suggest that 18β-GA may be used as a chemopreventive agent in liver cancer. PMID:27116616

  11. 18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

    PubMed

    Wang, Di; Zhang, Yongfeng; Wang, Chunyue; Jia, Dongxu; Cai, Guangsheng; Lu, Jiahui; Wang, Di; Zhang, Zhang-Jin

    2016-09-01

    The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL. PMID:27161375

  12. Stearate organogel-gelatin hydrogel based bigels: physicochemical, thermal, mechanical characterizations and in vitro drug delivery applications.

    PubMed

    Sagiri, Sai Sateesh; Singh, Vinay K; Kulanthaivel, Senthilguru; Banerjee, Indranil; Basak, Piyali; Battachrya, M K; Pal, Kunal

    2015-03-01

    Over the past decade, researchers have been trying to develop alternative gel based formulations in comparison to the traditional hydrogels and emulgels. In this perspective, bigels were synthesized by mixing gelatin hydrogel and stearic acid based organogel by hot emulsification method. Two types of bigels were synthesized using sesame oil and soy bean oil based stearate organogels. Gelatin based emulgels prepared using sesame oil and soy bean oil were used as the controls. Microscopic studies revealed that the bigels contained aggregates of droplets, whereas, emulgels showed dispersed droplets within the continuum phase. The emulgels showed higher amount of leaching of oils, whereas, the leaching of the internal phase was negligible from the bigels. Presence of organogel matrix within the bigels was confirmed by XRD, FTIR and DSC methods. Bigels showed higher mucoadhesive and mechanical properties compared to emulgels. Cyclic creep-recovery and stress relaxation studies confirmed the viscoelastic nature of the formulations. Four elemental Burger's model was employed to analyze the cyclic creep-recovery data. Cyclic creep-recovery studies suggested that the deformation of the bigels were lower due to the presence of the organogels within its structure. The formulations showed almost 100% recovery after the creep stage and can be explained by the higher elastic nature of the formulations. Stress relaxation study showed that the relaxation time was higher in the emulgels as compared to the bigels. Also, the % relaxation was higher in emulgels suggesting its fluid dominant nature. The in vitro biocompatibility of the bigels was checked using human epidermal keratinocyte cell line (HaCaT). Both emulgels and bigels were biocompatible in nature. The in vitro drug (ciprofloxacin) release behavior indicated non-Fickian diffusion of the drug from the matrices. The drug release showed good antimicrobial effect against Escherichia coli. Based on the results, it was concluded

  13. Investigation of the potential for direct compaction of a fine ibuprofen powder dry-coated with magnesium stearate.

    PubMed

    Qu, Li; Zhou, Qi Tony; Gengenbach, Thomas; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Gamlen, Michael; Morton, David A V

    2015-05-01

    Intensive dry powder coating (mechanofusion) with tablet lubricants has previously been shown to give substantial powder flow improvement. This study explores whether the mechanofusion of magnesium stearate (MgSt), on a fine drug powder can substantially improve flow, without preventing the powder from being directly compacted into tablets. A fine ibuprofen powder, which is both cohesive and possesses a low-melting point, was dry coated via mechanofusion with between 0.1% and 5% (w/w) MgSt. Traditional low-shear blending was also employed as a comparison. No significant difference in particle size or shape was measured following mechanofusion. For the low-shear blended powders, only marginal improvement in flowability was obtained. However, after mechanofusion, substantial improvements in the flow properties were demonstrated. Both XPS and ToF-SIMS demonstrated high degrees of a nano-scale coating coverage of MgSt on the particle surfaces from optimized mechanofusion. The study showed that robust tablets were produced from the selected mechanofused powders, at high-dose concentration and tablet tensile strength was further optimized via addition of a Polyvinylpyrrolidone (PVP) binder (10% w/w). The tablets with the mechanofused powder (with or without PVP) also exhibited significantly lower ejection stress than those made of the raw powder, demonstrating good lubrication. Surprisingly, the release rate of drug from the tablets made with the mechanofused powder was not retarded. This is the first study to demonstrate such a single-step dry coating of model drug with MgSt, with promising flow improvement, flow-aid and lubrication effects, tabletability and also non-inhibited dissolution rate. PMID:24738790

  14. The products of the reduction of doxyl stearates in cells are hydroxylamines as shown by oxidation by 15N-perdeuterated Tempone.

    PubMed

    Chen, K; Swartz, H M

    1989-07-21

    The use of nitroxides in functional biological systems has increased greatly as it has become evident that such studies can provide valuable biophysical and metabolic data. This has led to a need to understand the nature of the metabolism of nitroxides and their products. This paper presents data indicating the value of 15N-perdeuterated Tempone specifically to indicate the amount of hydroxylamines that are present in a cellular system. Using this technique, we found that in the mammalian cells that we studied the principal or only products of reduction of doxyl stearates were the corresponding hydroxylamines. PMID:2546601

  15. Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson's disease: a pharmacoinformatics study.

    PubMed

    Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

    2015-01-01

    Parkinson's disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD. PMID:25565772

  16. Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA.

    PubMed

    Chen, Fengqian; Zhang, Jinming; He, Yao; Fang, Xiefan; Wang, Yitao; Chen, Meiwan

    2016-01-01

    It remains a challenge to increase drug tumor-specific accumulation as well as to achieve intracellular-controlled drug release for hepatocellular carcinoma (HCC) chemotherapy. Herein, we developed a dual-functional biodegradable micellar system constituted by glycyrrhetinic acid coupling poly(ethylene glycol)-disulfide linkage-poly(lactic-co-glycolic acid) (GA-PEG-SS-PLGA) to achieve both hepatoma-targeting and redox-responsive intracellular drug release. Tanshinone IIA (TAN IIA), an effective anti-HCC drug, was encapsulated. Notably, it exhibited rapid aggregation and faster drug release in 10 mM dithiothreitol compared with the redox-insensitive control. Furthermore, GA-decorated micelles revealed HCC-specific cellular uptake in human liver cancer HepG2 cells with an energy-dependent manner, in which micropinocytosis and caveolae-mediated endocytosis were demonstrated as the major cellular pathways. The enhanced cytotoxicity and pro-apoptotic effects against HepG2 cells in vitro were observed, mediated by up-regulation of the intracellular ROS level, the increased cell cycle arrest at S phase, enhanced necrocytosis and up-regulation of caspase 3/7, P38 protein expression. In addition, TAN IIA-loaded micelles had a significantly prolonged circulation time, improved bioavailability, and resulted in an increased accumulation of TAN IIA in the liver. With the synergistic effects of HCC-targeting and controlled drug release, TAN IIA-loaded GA-PEG-SS-PLGA micelles significantly inhibited tumor growth and increased survival time in a mouse HCC-xenograft model. Collectively, the GA-PEG-SS-PLGA micelles with HCC-targeting and redox-sensitive characters would provide a novel strategy to deliver TAN IIA effectively for HCC therapy. PMID:26484363

  17. Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study

    PubMed Central

    Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

    2015-01-01

    Parkinson’s disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD. PMID:25565772

  18. The liquorice root derivative glycyrrhetinic acid can ameliorate ionoregulatory disturbance in rainbow trout (Oncorhynchus mykiss) abruptly exposed to ion-poor water.

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2016-09-01

    To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50μg 18βGA/g diet) for 2weeks, then abruptly exposed to ion-poor water (IPW) for 24h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na(+)] and/or [Cl(-)] reduced in control and 50μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na(+)-K(+)-ATPase and H(+)-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na(+)-K(+)-ATPase and H(+)-ATPase activity were unaltered or decreased in 50μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill. PMID:27220746

  19. Development of Salvianolic acid B-Tanshinone II A-Glycyrrhetinic acid compound liposomes: formulation optimization and its effects on proliferation of hepatic stellate cells.

    PubMed

    Lin, Jiahao; Wang, Xiuli; Wu, Qing; Dai, Jundong; Guan, Huida; Cao, Weiyi; He, Liangying; Wang, Yurong

    2014-02-28

    The aim of this study was to systematically optimize and characterize the co-encapsulation process of Salvianolic acid B (Sal B), Tanshinone II A (TSN) and Glycyrrhetinic acid (GA) into liposomes. The liposomes (GTS-lip) were prepared using film hydration method combined with probe sonication to encapsulate two hydrophobic components (TSN and GA), and using pH gradient method to load hydrophilic component Sal B. The concentration of encapsulated drugs was measured by a reversed phase high performance liquid chromatography (RP-HPLC) method. Systematic optimization of encapsulation process was performed using single factor test, orthogonal test in combination with Box-Behnken Design. Optimum conditions are as follows: ratio of GA to lipid (w/w)=0.08, ratio of Sal B to lipid (w/w)=0.12 and pH of buffer=3.3. Based on the conditions mentioned above, encapsulation efficiency of Sal B, TSN and GA reached target levels: (96.03 ± 0.28)%, (80.63 ± 0.91)% and (88.56 ± 0.17)%, respectively. The GTS-lip had a unimodal size-distribution and a mean diameter of 191.3 ± 6.31 nm. Morphology determination of the GTS-lip indicated that the liposomes were spherical, and there was no free drug crystal in the visual field of transmission electron microscopy. Also, the ζ potential of GTS-lip was detected to be -11.6 ± 0.35 mV. In vitro release investigation of GTS-lip suggested that the release rate of GTS-lip significantly decreased compared to drug solution. The accumulative release percentage of TSN, GA and Sal B were 10% in 36 h, 4% in 36 h and 77% in 24 h. Meanwhile, GTS-lip exhibited definite activity on proliferative inhibition of hepatic stellate cells (HSC). GTS-lip decreased the viability of the HSC to higher than 75% at two high drug concentration groups in 24h. At the same time, GTS-lip of two low drug concentration groups increased the inhibition rates by 2.3 folds and 1.9 folds separately at 48 h compared to 24h. By contrast, inhibition activity of G-T-S solution group

  20. Adsorption of counter ions to a stearate monolayer spread at the water-air interface: A synchrotron x-ray study

    SciTech Connect

    Bloch, J.M.; Yun, W.B.; Yang, X. ); Montano, P.A. . Dept. of Physics); Ramanathan, M. ); Capasso, C. )

    1988-06-01

    The Near Total External Fluorescence (NTEF) technique was used to measure in-situ the adsorption of a metal ion from a subphase solution to the liquid-air interface, induced by a surfactant monolayer on the interface. For a monolayer formed by spreading stearic acid (a surfactant material) on a 10{sup {minus}3} mole/l solution of MnCl{sub 2}, the ratio of Mn ions segregated to the interface to the number of stearate molecules on the surface was determined to be approximately 0.6 {plus minus} 0.2. SEXAFS experiments revealed local order of the Mn ions at the surface at the condensed phase but no order showed up in the expanded phase. We explain these findings using a self consistent Poisson-Boltzman calculation of a partially ionized monolayer. Our model also explains earlier reports of adsorption of metal ions to the liquid/monolayer interface. 19 refs., 3 figs.

  1. Scale effects in tribological properties of solid-lubricating composites made of ultra-high molecular weight polyethylene filled with calcium stearate particles

    NASA Astrophysics Data System (ADS)

    Lurie, S. A.; Volkov-Bogorodskiy, D. B.; Knyzeva, A. G.; Panin, S. V.; Kornienko, L. A.

    2016-04-01

    Friction properties being influenced by scale effects are simulated in the paper by the example of polymer composite material made from Ultra High-Molecular Weight Polyethylenes (UHMWPE) filled by calcium stearate (C36H70CaO4). Of interest are the composites whose mechanical properties and tribotechnical characteristics do not depend monotonically on filler (inclusions) weight fraction. In order to describe the influence of scale effects onto frictional properties the model based on Reiss averaging (model of "weak phase") is employed. It is also suggested that when gradient elasticity theory is applicable the formal analogy between effective friction coefficient for surface heterogeneous structures and effective mechanical properties (compliances) for heterogeneous material can take place. Theoretical dependence to describe nonmonotonic change of effective friction coefficient versus filler concentration was obtained for the polymer composites under study. The suggested expressions might be useful for the sake of properties prognosis of antifriction polymeric materilas.

  2. Effect of molecular weight, calcium stearate, and sterilization methods on the wear of ultra high molecular weight polyethylene acetabular cups in a hip joint simulator.

    PubMed

    McKellop, H A; Shen, F W; Campbell, P; Ota, T

    1999-05-01

    Orthopaedic surgeons must currently choose from several types of ultra high molecular weight polyethylene acetabular cups that differ in their material properties and in the methods used for their sterilization. Information on the wear resistance of these different cups may help in the selection process. This study included two separate tests for wear run on a hip simulator to investigate the effect of molecular weight, calcium stearate, and sterilization methods on the wear resistance of ultra high molecular weight polyethylene acetabular cups. Test 1 revealed nearly identical wear rates for acetabular cups with molecular weights in two distinct ranges, as well as for cups with molecular weights in the same range but with or without calcium stearate added. In Test 2, cups that were sterilized in air with gamma irradiation exhibited lower rates of wear than those sterilized with ethylene oxide, presumably due to the crosslinking induced by the irradiation. In addition, cups that were irradiated while packed in a partial vacuum to minimize oxygen absorbed in the surface layer initially showed lower rates of wear than those irradiated in air, with the wear rates becoming similar as wear penetrated the more oxidized surface layer and the more crosslinked subsurface region. Because these tests were run a few months after the irradiation, the potential effects of long-term oxidation of any residual free radicals in the irradiated materials could not be taken into account. After artificial aging to accelerate oxidative degradation of the materials, the wear rates could be markedly different. Analyses performed after wear indicated that the irradiated (i.e., crosslinked) cups exhibited a smaller proportion of, as well as shorter, fibrils in the wear debris and an increased crystallinity and melting temperature and that gamma irradiation in the low-oxygen environment reduced the level of oxidation and increased the level of crosslinking in the surface region of the cups

  3. Simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid in rat plasma by HPLC-MS/MS: application to a pharmacokinetic study of Longhu Rendan pills.

    PubMed

    Wang, Tianming; Ding, Liqing; Jin, Huajia; Shi, Rong; Li, Yuanyuan; Wu, Jiasheng; Li, Yifei; Zhu, Li; Ma, Yueming

    2016-08-01

    A sensitive, specific, accurate HPLC-MS/MS method was developed and validated for the simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid from Longhu Rendan pills in rat plasma. Chromatographic separation was performed with a Hypersil Gold C18 column using a gradient of methanol and 0.01% acetic acid containing 0.2 mm ammonium acetate as mobile phase. The analytes were quantified on a triple quadrupole mass spectrometer, operating in selected reaction monitoring mode and switching the electrospray ion source polarity between positive and negative modes in a single run. The calibration curves of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid were linear over the concentration ranges of 5-2000, 5-2000, 0.5-200, 0.5-200, 0.25-100, 0.25-100, 0.025-10 and 0.50-200 ng mL(-1) , respectively. The intra- and inter-assay precisions and accuracies were <11.6 and 91.9-108.2%, respectively, for all analytes. Matrix effects for all analytes were between 88.2 and 114.2%. Stability testing showed that all analytes were stable in plasma at 24 °C for 3 h, at 4 °C for 24 h, after three freeze-thaw cycles, and at -80 °C for 15 days. The method was successfully applied to an in vivo study evaluating the pharmacokinetics of multiple nonvolatile compounds following intragastric administration of Longhu Rendan pills to rats. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26613237

  4. Isotopologue profiling of triterpene formation under physiological conditions. Biosynthesis of lupeol-3-(3'-R-hydroxy)-stearate in Pentalinon andrieuxii.

    PubMed

    Peña-Rodríguez, Luis M; Yam-Puc, Alejandro; Knispel, Nihat; Schramek, Nicholas; Huber, Claudia; Graßberger, Christoph; Ramírez-Torres, Fabiola G; Escalante-Erosa, Fabiola; García-Sosa, Karlina; Hiebert-Giesbrecht, Mickel R; Chan-Bacab, Manuel J; Godoy-Hernández, Gregorio; Bacher, Adelbert; Eisenreich, Wolfgang

    2014-04-01

    The biosynthesis of lupeol-3-(3'R-hydroxy)-stearate (procrim b, 1) was investigated in the Mexican medicinal plant Pentalinon andrieuxii by (13)CO2 pulse-chase experiments. NMR analyses revealed positional enrichments of (13)C2-isotopologues in both the triterpenoid and the hydroxystearate moieties of 1. Five of the six isoprene units reflected a pattern with [1,2-(13)C2]- and [3,5-(13)C2]-isotopologues from the respective C5-precursors, IPP and DMAPP, whereas one isoprene unit in the ring E of 1 showed only the [3,5-(13)C2]-connectivity of the original C5-precursor, due to rearrangement of the dammarenyl cation intermediate during the cyclization process. The presence of (13)C2-isotopologues was indicative of [(13)C2]acetyl-CoA being the precursor units in the formation of the fatty acid moiety and of the triterpene via the mevalonate route. The observed labeling pattern was in agreement with a chair-chair-chair-boat conformation of the (S)-2,3-oxidosqualene precursor during the cyclization process, suggesting that the lupeol synthase from P. andrieuxii is of the same type as that from Olea europea and Taraxacum officinale, but different from that of Arabidopsis thaliana. The study shows that (13)CO2 pulse-chase experiments are powerful in elucidating, under in vivo conditions and in a single experiment, the biosynthesis of complex plant products including higher terpenes. PMID:24606167

  5. Enzymatic interesterification of soybean oil and methyl stearate blends using lipase immobilized on magnetic Fe3O4/SBA-15 composites as a biocatalyst.

    PubMed

    Zang, Xuezhen; Xie, Wenlei

    2014-01-01

    The magnetic Fe3O4/SBA-15 composites were prepared, and treated with 3-aminopropyltriethoxysilane as a carrier material for enzyme immobilization. The immobilization of Candida rugosa lipase onto the amino-functionalized Fe3O4/SBA-15 composite was investigated by using glutaraldehyde as a coupling reagent. The immobilized lipase was then employed as a biocatalyst for the interesterification of soybean oil and methyl stearate in a laboratory-scale operation at 45°C. Various techniques, such as Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), and vibrating sample magnetometry (VSM), were used for the characterization of the immobilized lipase composite. The immobilized lipase behaved superparamagnetic and showed excellent response at applied magnetic field. The obtained results showed that the immobilized lipase could efficiently catalyze the interesterification reaction. Moreover, the interesterification reaction parameters, such as reaction temperature, substrate ratio and reaction time were investigated regarding the stearoyl incorporation into the triacylglycerols. Further, the immobilized lipase proved to be easily separated from the reaction mixture by applying an external magnetic field and to be stable in the repeated use for four cycles. PMID:25213444

  6. Incorporating Turbula mixers into a blending scale-up model for evaluating the effect of magnesium stearate on tablet tensile strength and bulk specific volume.

    PubMed

    Kushner, Joseph

    2012-06-15

    Turbula bottle blenders are often used in lab-scale experiments during early-stage pharmaceutical product development. Unfortunately, applying knowledge gained with these blenders to larger-sized diffusion mixers is limited by the lack of blending models that include Turbula mixers. To address this need for lubrication blending scale-up, 2:1 blends of microcrystalline cellulose and spray-dried lactose or dibasic calcium phosphate were mixed with 1% magnesium stearate using Turbula bottle blenders, varying bottle volume, V (30-1250mL); bottle headspace fraction, F(headspace) (30-70%); and the number of blending cycles, r (24 to ∼190,000 cycles). The impact of lubrication blending on tensile strength and bulk specific volume quality attributes, QA, was modeled by:where QA(0) is initial QA value, β is sensitivity of QA to lubrication, γ is formulation-specific lubrication rate constant, and L is characteristic mixing length scale (i.e. 1.5V(1/3) for Turbula blenders, V(1/3) for simple diffusion mixers). The factor of 1.5 captures the bottle dimensions and the more complex mixing dynamics of the Turbula blender. This lubrication blending process model is valid for scale-up from 30-mL to 200-L blenders. Assessing bulk specific volume may provide a simpler, more material-sparing means for determining γ than tensile strength, since these QAs exhibited similar γ values. PMID:22405966

  7. The Effect of Zn-Al-Hydrotalcites Composited with Calcium Stearate and β-Diketone on the Thermal Stability of PVC

    PubMed Central

    Tong, Mengliang; Chen, Hongyan; Yang, Zhanhong; Wen, Runjuan

    2011-01-01

    A clean-route synthesis of Zn-Al-hydrotalcites (Zn-Al-LDHs) using zinc oxide and sodium aluminate solution has been developed. The as-obtained materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The effects of metal ions at different molar ratios on the performance of hydrotalcites were discussed. The results showed that the Zn-Al-hydrotalcites can be successfully synthesized at three different Zn/Al ratios of 3:1, 2:1 and 1:1. Thermal aging tests of polyvinyl chloride (PVC) mixed with Zn-Al-LDHs, calcium stearate (CaSt2) and β-diketone were carried out in a thermal aging test box by observing the color change. The results showed that Zn-Al-LDHs can not only enhance the stability of PVC significantly due to the improved capacity of HCl-adsorption but also increase the initial stability and ensure good-initial coloring due to the presence of the Zn element. The effects of various amounts of Zn-Al-LDHs, CaSt2 and β-diketone on the thermal stability of PVC were discussed. The optimum composition was determined to be 0.1 g Zn-Al-LDHs, 0.15 g CaSt2 and 0.25 g β-diketone in 5 g PVC. PMID:21673921

  8. Immobilized metal affinity chromatography on collapsed Langmuir-Blodgett iron(III) stearate films and iron(III) oxide nanoparticles for bottom-up phosphoproteomics.

    PubMed

    Gladilovich, Vladimir; Greifenhagen, Uta; Sukhodolov, Nikolai; Selyutin, Artem; Singer, David; Thieme, Domenika; Majovsky, Petra; Shirkin, Alexey; Hoehenwarter, Wolfgang; Bonitenko, Evgeny; Podolskaya, Ekaterina; Frolov, Andrej

    2016-04-22

    Phosphorylation is the enzymatic reaction of site-specific phosphate transfer from energy-rich donors to the side chains of serine, threonine, tyrosine, and histidine residues in proteins. In living cells, reversible phosphorylation underlies a universal mechanism of intracellular signal transduction. In this context, analysis of the phosphoproteome is a prerequisite to better understand the cellular regulatory networks. Conventionally, due to the low contents of signaling proteins, selective enrichment of proteolytic phosphopeptides by immobilized metal affinity chromatography (IMAC) is performed prior to their LC-MS or -MS/MS analysis. Unfortunately, this technique still suffers from low selectivity and compromised analyte recoveries. To overcome these limitations, we propose IMAC systems comprising stationary phases based on collapsed Langmuir-Blodgett films of iron(III) stearate (FF) or iron(III) oxide nanoparticles (FO) and mobile phases relying on ammonia, piperidine and heptadecafluorooctanesulfonic acid (PFOS). Experiments with model phosphopeptides and phosphoprotein tryptic digests showed superior binding capacity, selectivity and recovery for both systems in comparison to the existing commercial analogs. As evidenced by LC-MS/MS analysis of the HeLa phosphoproteome, these features of the phases resulted in increased phosphoproteome coverage in comparison to the analogous commercially available phases, indicating that our IMAC protocol is a promising chromatographic tool for in-depth phosphoproteomic research. PMID:27016113

  9. The effect of Zn-Al-hydrotalcites composited with calcium stearate and β-diketone on the thermal stability of PVC.

    PubMed

    Tong, Mengliang; Chen, Hongyan; Yang, Zhanhong; Wen, Runjuan

    2011-01-01

    A clean-route synthesis of Zn-Al-hydrotalcites (Zn-Al-LDHs) using zinc oxide and sodium aluminate solution has been developed. The as-obtained materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The effects of metal ions at different molar ratios on the performance of hydrotalcites were discussed. The results showed that the Zn-Al-hydrotalcites can be successfully synthesized at three different Zn/Al ratios of 3:1, 2:1 and 1:1. Thermal aging tests of polyvinyl chloride (PVC) mixed with Zn-Al-LDHs, calcium stearate (CaSt(2)) and β-diketone were carried out in a thermal aging test box by observing the color change. The results showed that Zn-Al-LDHs can not only enhance the stability of PVC significantly due to the improved capacity of HCl-adsorption but also increase the initial stability and ensure good-initial coloring due to the presence of the Zn element. The effects of various amounts of Zn-Al-LDHs, CaSt(2) and β-diketone on the thermal stability of PVC were discussed. The optimum composition was determined to be 0.1 g Zn-Al-LDHs, 0.15 g CaSt(2) and 0.25 g β-diketone in 5 g PVC. PMID:21673921

  10. Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers.

    PubMed

    Wang, Z Y; Agarwal, R; Zhou, Z C; Bickers, D R; Mukhtar, H

    1991-02-01

    Licorice has been used as medicine and as sweetening agent in food products. The major water-soluble constituent of licorice is glycyrrhizin (GL), an oleanane triterpenoide, which is known to be partly hydrolyzed by glucuronidase to its aglycone glycyrrhetinic acid (GA) which exists in 18 alpha (alpha-GA) and 18 beta (beta-GA) stereoisomeric forms. In this study alpha-GA and beta-GA were found to inhibit the mutagenicity of benzo[a]pyrene (B[a]P), 2-aminofluorene and aflatoxin B1 in Salmonella typhimurium TA98 and TA100. beta-GA was more effective than alpha-GA as an antimutagen. In the two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the tumor initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter, pretreatment of SENCAR mice with alpha-GA or beta-GA resulted in significant protection against tumor initiation as well as tumor promotion. As an anti-tumor initiating agent, beta-GA was found to be more effective than alpha-GA. Similarly, topical application of beta-GA was found to be more effective than alpha-GA in inhibiting the binding of both [3H]B[a]P and [3H]DMBA to epidermal DNA. However, as an anti-tumor promoter, alpha-GA and beta-GA showed comparable effects. Our results suggest that both alpha-GA and beta-GA possess substantial anti-skin tumor initiating and anti-skin tumor promoting activities. PMID:1899808

  11. Methyl 2-Cyano-3,11-dioxo-18-olean-1,12-dien-30-oate (CDODA-Me), a Derivative of Glycyrrhetinic Acid, Functions as a Potent Angiogenesis Inhibitor

    PubMed Central

    Pang, Xiufeng; Zhang, Li; Wu, Yougen; Lin, Lei; Li, Jingjie; Qu, Weijing; Safe, Stephen

    2010-01-01

    Methyl 2-cyano-3,11-dioxo-18-olean-1,12-dien-30-oate (CDODA-Me), a triterpenoid acid derived synthetically from glycyrrhetinic acid, has been characterized as a peroxisome proliferator-activated receptor γ agonist with a broad range of receptor-dependent and -independent anticancer activities. Although CDODA-Me decreases the expression of some angiogenic genes in cancer cells, the direct effects of this compound on angiogenesis have not been defined. In this study, we have extensively investigated the activities of CDODA-Me in multiple angiogenesis assays. Our results showed that this agent inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, and lamellipodium and capillary-like structure formation of human umbilical endothelial cells (HUVECs) in a concentration-dependent manner. Moreover, CDODA-Me abrogated VEGF-induced sprouting of microvessels from rat aortic rings ex vivo and inhibited the generation of new vasculature in the Matrigel plugs in vivo, where CDODA-Me significantly decreased the number of infiltrating von Willebrand factor-positive endothelial cells. To understand the molecular basis of this antiangiogenic activity, we examined the signaling pathways in CDODA-Me-treated HUVECs. Our results showed that CDODA-Me significantly suppressed the activation of VEGF receptor 2 (VEGFR2) and interfered with the mammalian target of rapamycin (mTOR) signaling, including mTOR kinase and its downstream ribosomal S6 kinase (S6K), but had little effect on the activities of extracellular signal-regulated protein kinase and AKT. Taken together, CDODA-Me blocks several key steps of angiogenesis by inhibiting VEGF/VEGFR2 and mTOR/S6K signaling pathways, making the compound a promising agent for the treatment of cancer and angiogenesis-related pathologies. PMID:20631299

  12. 21 CFR 184.1229 - Calcium stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or available for inspection at the National Archives and Records Administration (NARA). For information on the availability of...

  13. Final report on the safety assessment of trilaurin, triarachidin, tribehenin, tricaprin, tricaprylin, trierucin, triheptanoin, triheptylundecanoin, triisononanoin, triisopalmitin, triisostearin, trilinolein, trimyristin, trioctanoin, triolein, tripalmitin, tripalmitolein, triricinolein, tristearin, triundecanoin, glyceryl triacetyl hydroxystearate, glyceryl triacetyl ricinoleate, and glyceryl stearate diacetate.

    PubMed

    Johnson, W

    2001-01-01

    : Trilaurin, Triarachidin, Tribehenin, Tricaprin, Tricaprylin, Trierucin, Triheptanoin, Triheptylundecanoin, Triisononanoin, Triisopalmitin, Triisostearin, Trilinolein, Trimyristin, Trioctanoin, Triolein, Tripalmitin, Tripalmitolein, Triricinolein, Tristearin, Triundecanoin, Glyceryl Triacetyl Hydroxystearate, Glyceryl Triacetyl Ricinoleate, and Glyceryl Stearate Diacetate. Some of these are not currently in use, but would be considered safe if used at concentrations similar to those glyceryl triesters that are in use as cosmetic ingredients. PMID:11800053

  14. 21 CFR 178.3690 - Pentaerythritol adipate-stearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Number (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference... (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference. Copies...

  15. 21 CFR 178.3690 - Pentaerythritol adipate-stearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., “Standard Test Method for Saponification Number (Empirical) of Synthetic and Natural Waxes” (Revised 1978... D1387-78, “Standard Test Method for Acid Number (Empirical) of Synthetic and Natural Waxes”...

  16. 21 CFR 178.3690 - Pentaerythritol adipate-stearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Number (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference... (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference. Copies...

  17. 21 CFR 178.3690 - Pentaerythritol adipate-stearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Number (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference... (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference. Copies...

  18. 21 CFR 178.3690 - Pentaerythritol adipate-stearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Number (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference... (Empirical) of Synthetic and Natural Waxes” (Revised 1978), which is incorporated by reference. Copies...

  19. Synthesis of Branched Methyl Hydroxy Stearates Including an Ester from Bio-Based Levulinic Acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the synthesis of 5 useful branched methyl alpha-hydroxy oleate esters from commercially available methyl oleate and common organic acids. Of special interest is the synthesis utilizing the natural byproduct, levulinic acid. The other common organic acids used herein were propionic acid, ...

  20. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... surface of calcium carbonate at a level not to exceed 1 weight-percent of the total mixture. (b) The calcium carbonate/glyceryl tri-(12-acetoxystearate) mixture is used as an adjuvant in polymers in...

  1. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... surface of calcium carbonate at a level not to exceed 1 weight-percent of the total mixture. (b) The calcium carbonate/glyceryl tri-(12-acetoxystearate) mixture is used as an adjuvant in polymers in...

  2. Interfacial, stability and rheological study of microbubbles coated with a monostearin/monopalmitin-rich food emulsifier and PEG40 stearate

    NASA Astrophysics Data System (ADS)

    Shen, Yuyi

    Micron-scale bubbles (microbubbles) are of considerable interest in environmental, biomedical, and food sciences. The low cost food emulsifiers, which are used to stabilize the gas core of the microbubble, consist of a mixture of monoglycerides, diglycerides and sodium steroyl lactylate in combination with polyethylene glycol (PEG) 40 sterate. Langmuir trough methods and fluorescence microscopy were combined to investigate the surface tension, interfacial elastic modulus, phase behavior and microstructure of monolayer shells coating these microbubbles. Polydisperse coated microbubbles can be generated using a probe sonication technique. The dissolution behavior of a microbubble in different unsaturated media was studied using a fluorescence microscope. These dissolution behaviors, involving the buckling and rupture of the coated monolayer, can be explained by the phase behavior of emulsifiers and their roles in the stabilization of microbubbles in aqueous systems. Nearly monodispersed populations of microbubbles ranged in 120--200mum were produced using flow focusing Technique. Sufficient short-term stability in size allows the rheological properties of microbubble suspension to be obtained by rheometer. The effect of shearing on the bubble sizes is investigated. There results show that the microbubble suspensions are viscoelastic and exhibit power law behavior. The relationship between the air fraction of the suspension and fluid rheology is determined.

  3. A potential adjuvant chemotherapeutics, 18β-glycyrrhetinic acid, inhibits renal tubular epithelial cells apoptosis via enhancing BMP-7 epigenetically through targeting HDAC2

    PubMed Central

    Ma, Taotao; Huang, Cheng; Meng, Xiaoming; Li, Xiaofeng; Zhang, Yilong; Ji, Shuai; Li, Jun; Ye, Min; Liang, Hong

    2016-01-01

    Cisplatin, a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy by an effective adjuvant via epigenetic modification through targeting HDAC2. Molecular docking and SPR assay firstly reported that 18βGA, major metabolite of GA, could directly bind to HDAC2 and inhibit the activity of HDAC2. The effects and mechanisms of GA and 18βGA were assessed in CP-induced AKI in C57BL/6 mice, and in CP-treated HK-2 and mTEC cells lines. TUNEL and FCM results confirmed that GA and 18βGA could inhibit apoptosis of renal tubular epithelial cells induced by CP in vivo and in vitro. Western blot and immunofluorescence results demonstrated that the expression of BMP-7 was clearly induced by 18βGA in AKI models while siRNA BMP-7 could reduce the inhibitory effect of 18βGA on apoptosis. Results of current study indicated that 18βGA inhibited apoptosis of renal tubular epithelial cells via enhancing the level of BMP-7 epigenetically through targeting HDAC2, therefore protecting against CP-induced AKI. These available evidence, which led to an improved understanding of molecular recognition, suggested that 18βGA could serve as a potential clinical adjuvant in chemotherapy. PMID:27145860

  4. Functional Characterization of Two Structurally Novel Diacylglycerol Acyltransferase2 Isozymes Responsible for the Enhanced Production of Stearate-Rich Storage Lipid in Candida tropicalis SY005

    PubMed Central

    Dey, Prabuddha; Chakraborty, Monami; Kamdar, Maulik R.; Maiti, Mrinal K.

    2014-01-01

    Diacylglycerol acyltransferase (DGAT) activity is an essential enzymatic step in the formation of neutral lipid i.e., triacylglycerol in all living cells capable of accumulating storage lipid. Previously, we characterized an oleaginous yeast Candida tropicalis SY005 that yields storage lipid up to 58% under a specific nitrogen-stress condition, when the DGAT-specific transcript is drastically up-regulated. Here we report the identification, differential expression and function of two DGAT2 gene homologues- CtDGAT2a and CtDGAT2b of this C. tropicalis. Two protein isoforms are unique with respect to the presence of five additional stretches of amino acids, besides possessing three highly conserved motifs known in other reported DGAT2 enzymes. Moreover, the CtDGAT2a and CtDGAT2b are characteristically different in amino acid sequences and predicted protein structures. The CtDGAT2b isozyme was found to be catalytically 12.5% more efficient than CtDGAT2a for triacylglycerol production in a heterologous yeast system i.e., Saccharomyces cerevisiae quadruple mutant strain H1246 that is inherently defective in neutral lipid biosynthesis. The CtDGAT2b activity rescued the growth of transformed S. cerevisiae mutant cells, which are usually non-viable in the medium containing free fatty acids by incorporating them into triacylglycerol, and displayed preferential specificity towards saturated acyl species as substrate. Furthermore, we document that the efficiency of triacylglycerol production by CtDGAT2b is differentially affected by deletion, insertion or replacement of amino acids in five regions exclusively present in two CtDGAT2 isozymes. Taken together, our study characterizes two structurally novel DGAT2 isozymes, which are accountable for the enhanced production of storage lipid enriched with saturated fatty acids inherently in C. tropicalis SY005 strain as well as in transformed S. cerevisiae neutral lipid-deficient mutant cells. These two genes certainly will be useful for further investigation on the novel structure-function relationship of DGAT repertoire, and also in metabolic engineering for the enhanced production of lipid feedstock in other organisms. PMID:24732323

  5. Glycyrrhetinic acid induces cytoprotective autophagy via the inositol-requiring enzyme 1α-c-Jun N-terminal kinase cascade in non-small cell lung cancer cells

    PubMed Central

    Tang, Zheng-Hai; Zhang, Le-Le; Li, Ting; Lu, Jia-Hong; Ma, Dik-Lung; Leung, Chung-Hang; Chen, Xiu-Ping; Jiang, Hu-Lin; Wang, Yi-Tao; Lu, Jin-Jian

    2015-01-01

    Glycerrhetinic acid (GA), one of the main bioactive constituents of Glycyrrhiza uralensis Fisch, exerts anti-cancer effects on various cancer cells. We confirmed that GA inhibited cell proliferation and induced apoptosis in non-small cell lung cancer A549 and NCI-H1299 cells. GA also induced expression of autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and punta formation of green fluorescent protein microtubule-associated protein light-chain 3. We further proved that expression of GA-increased autophagy marker was attributed to activation instead of suppression of autophagic flux. The c-jun N-terminal kinase (JNK) pathway was activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. The endoplasmic reticulum (ER) stress responses were also apparently stimulated by GA by triggering the inositol-requiring enzyme 1α (IRE1α) pathway. The GA-induced JNK pathway activation and autophagy were decreased by IRE1α knockdown, and inhibition of autophagy or the JNK cascade increased GA-stimulated IRE1α expression. In addition, GA-induced cell proliferative inhibition and apoptosis were increased by inhibition of autophagy or the JNK pathway. Our study was the first to demonstrate that GA induces cytoprotective autophagy in non-small cell lung cancer cells by activating the IRE1α-JNK/c-jun pathway. The combined treatment of autophagy inhibitors markedly enhances the anti-neoplasmic activity of GA. Such combination shows potential as a strategy for GA or GA-contained prescriptions in cancer therapy. PMID:26549806

  6. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate....

  7. Ionic liquid 1-butyl-3-methylimidazolium cyanamide (bmim [dca]) as a solvent and catalyst for acylation of maltodextrin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have found a novel method to prepare maltodextrin stearate with DS upto 0.60 in 90% yields from maltodextrin in IL bmim[dca] reacted with vinyl stearate or stearic acid. In this work we have demonstrated that IL could simultaneously act as a solvent and as a catalyst for reaction of maltodextrin...

  8. Ionic Liquid as a Solvent and Catalyst for Acylation of Maltodextrin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Catalyst-free esterification of maltodextrin was carried out in ionic liquid. Stearate esters of maltodextrin were obtained in various degree of substitution (DS) when vinyl stearate or stearic acid was heated with maltodextrin in ionic liquid, 1-butyl-3-methylimidazolium cyanamide (bmim[dca]). Re...

  9. Preparation and characterization of polyhydroxybutyrate/polycaprolactone nanocomposites.

    PubMed

    Liau, Cha Ping; Bin Ahmad, Mansor; Shameli, Kamyar; Yunus, Wan Md Zin Wan; Ibrahim, Nor Azowa; Zainuddin, Norhazlin; Then, Yoon Yee

    2014-01-01

    Polyhydroxybutyrate (PHB)/polycaprolactone (PCL)/stearate Mg-Al layered double hydroxide (LDH) nanocomposites were prepared via solution casting intercalation method. Coprecipitation method was used to prepare the anionic clay Mg-Al LDH from nitrate salt solution. Modification of nitrate anions by stearate anions between the LDH layers via ion exchange reaction. FTIR spectra showed the presence of carboxylic acid (COOH) group which indicates that stearate anions were successfully intercalated into the Mg-Al LDH. The formation of nanocomposites only involves physical interaction as there are no new functional groups or new bonding formed. X-ray diffraction (XRD) and transmission electron microscopy (TEM) indicated that the mixtures of nanocomposites are intercalated and exfoliated types. XRD results showed increasing of basal spacing from 8.66 to 32.97 Å in modified stearate Mg-Al LDH, and TEM results revealed that the stearate Mg-Al LDH layers are homogeneously distributed in the PHB/PCL polymer blends matrix. Enhancement in 300% elongation at break and 66% tensile strength in the presence of 1.0 wt % of the stearate Mg-Al LDH as compare with PHB/PCL blends. Scanning electron microscopy (SEM) proved that clay improves compatibility between polymer matrix and the best ratio 80PHB/20PCL/1stearate Mg-Al LDH surface is well dispersed and stretched before it breaks. PMID:24600329

  10. Preparation and Characterization of Polyhydroxybutyrate/Polycaprolactone Nanocomposites

    PubMed Central

    Liau, Cha Ping; Bin Ahmad, Mansor; Shameli, Kamyar; Yunus, Wan Md Zin Wan

    2014-01-01

    Polyhydroxybutyrate (PHB)/polycaprolactone (PCL)/stearate Mg-Al layered double hydroxide (LDH) nanocomposites were prepared via solution casting intercalation method. Coprecipitation method was used to prepare the anionic clay Mg-Al LDH from nitrate salt solution. Modification of nitrate anions by stearate anions between the LDH layers via ion exchange reaction. FTIR spectra showed the presence of carboxylic acid (COOH) group which indicates that stearate anions were successfully intercalated into the Mg-Al LDH. The formation of nanocomposites only involves physical interaction as there are no new functional groups or new bonding formed. X-ray diffraction (XRD) and transmission electron microscopy (TEM) indicated that the mixtures of nanocomposites are intercalated and exfoliated types. XRD results showed increasing of basal spacing from 8.66 to 32.97 Å in modified stearate Mg-Al LDH, and TEM results revealed that the stearate Mg-Al LDH layers are homogeneously distributed in the PHB/PCL polymer blends matrix. Enhancement in 300% elongation at break and 66% tensile strength in the presence of 1.0 wt % of the stearate Mg-Al LDH as compare with PHB/PCL blends. Scanning electron microscopy (SEM) proved that clay improves compatibility between polymer matrix and the best ratio 80PHB/20PCL/1stearate Mg-Al LDH surface is well dispersed and stretched before it breaks. PMID:24600329

  11. [Comparison of two extraction methods for maxingshigan decoction].

    PubMed

    Zhang, Z; Sun, X; Wang, L; Liu, H; Lu, Q

    1997-07-01

    The semi-bionic extraction and the extraction with water, two methods for the Maxingshigan Decoction, were compared. The results show that the semi-bionic extraction is superior to the extraction with water in the yield of ephedrine, hydrocyanic acid, glycyrrhetinic acid, calcium ion and extract. PMID:11038900

  12. Viscosity Depressants for Coal Liquefaction

    NASA Technical Reports Server (NTRS)

    Kalfayan, S. H.

    1983-01-01

    Proposed process modification incorporates viscosity depressants to prevent coal from solidifying during liquefaction. Depressants reduce amount of heat needed to liquefy coal. Possible depressants are metallic soaps, such as stearate, and amides, such as stearamide and dimer acid amides.

  13. 40 CFR 414.70 - Applicability; description of the bulk organic chemicals subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... *Alkylates *Alpha-Olefins Butane (all forms) *C-4 Hydrocarbons (Unsaturated) Calcium Stearate Caprolactam...-Ethylbutyraldehyde 2,2,4-Trimethyl-1,3-Pentanediol (b) Amine and Amide Organic Chemicals 2,4-Diaminotoluene...

  14. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  15. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  16. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  17. 21 CFR 169.179 - Vanilla powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... anticaking ingredients referred to in paragraph (a) of this section are: (1) Aluminum calcium silicate. (2) Calcium silicate. (3) Calcium stearate. (4) Magnesium silicate. (5) Tricalcium phosphate. (c)(1)...

  18. 21 CFR 169.179 - Vanilla powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... anticaking ingredients referred to in paragraph (a) of this section are: (1) Aluminum calcium silicate. (2) Calcium silicate. (3) Calcium stearate. (4) Magnesium silicate. (5) Tricalcium phosphate. (c)(1)...

  19. 21 CFR 169.179 - Vanilla powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... anticaking ingredients referred to in paragraph (a) of this section are: (1) Aluminum calcium silicate. (2) Calcium silicate. (3) Calcium stearate. (4) Magnesium silicate. (5) Tricalcium phosphate. (c)(1)...

  20. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  1. Possible explanation for the white band artifact seen in clinically retrieved polyethylene tibial components.

    PubMed

    Willie, B M; Gingell, D T; Bloebaum, R D; Hofmann, A A

    2000-12-01

    Studies have focused attention on the appearance of a subsurface white band in clinically retrieved polyethylene components and the possible contribution of this phenomenon to early polyethylene delamination. Unconsolidated polyethylene particles and oxidation have been suggested as possible reasons for the appearance of the white band. Calcium stearate and other additives used in processing ultra-high molecular weight polyethylene may also contribute to formation of the white band. A quantitative investigation was conducted on 11 retrieved tibial components that exhibited a subsurface white band to determine whether the amount of calcium stearate particles and additives were greater in the white band region when compared with the mid-portion of the same section of polyethylene. Calcium stearate particles and other additives were quantified using backscattered electron imaging with correlated elemental analysis. The particles were identified based on morphology and elemental patterns similar to reference calcium stearate particles and known additives. Significantly more (p < 0. 0001) calcium stearate particles and additives were present in the white band region (4578 +/- 418 particles/mm(2); mean +/- standard error) than the mid-portion region (1250 +/- 147 particles/mm(2)) of the sectioned tibial inserts. The percent area occupied by calcium stearate particles and additives was five times higher (p < 0.0001) within the white band region (0.81 +/- 0.10%) than the mid-portion region (0.16 +/- 0.03%). The increased presence of calcium stearate and other additives in the white band region suggests that they may play a role in the formation of the white band. In future investigations it may be important to consider how calcium stearate and other additives in polyethylene resins affect white band formation and the possible contribution to crazing, early delamination, and osteolysis in total joint replacement. PMID:11007625

  2. Final report of the safety assessment of allantoin and its related complexes.

    PubMed

    Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Klaassen, Curtis D; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Alan Andersen, F

    2010-05-01

    Allantoin is a heterocyclic organic compound. Allantoin ascorbate, allantoin biotin, allantoin galacturonic acid, allantoin glycyrrhetinic acid, allantoin panthenol, and allantoin polygalacturonic acid are complexes of allantoin. All of the ingredients in this review act as skin-conditioning agents. Allantoin was reported to be used in 1376 cosmetic products at concentrations up to 2%. There are data gaps regarding use and concentration of the remaining allantoin complexes. Ascorbic acid, biotin, glycyrrhetinic acid, and panthenol have been determined by the CIR Expert Panel to be safe. Galacturonic acid and polygalacturonic acid have not been reviewed by the CIR Expert Panel, and substantial data on these chemicals were not available. The safety test data in this safety assessment and in previous safety assessments were considered sufficient to support the safety of allantoin and the allantoin complexes in product categories and at concentrations reviewed in this safety assessment. PMID:20448269

  3. Analysis of bioactive components and pharmacokinetic study of herb-herb interactions in the traditional Chinese patent medicine Tongmai Yangxin Pill.

    PubMed

    Fan, Yaya; Man, Shuli; Li, Hongfa; Liu, Yuanxue; Liu, Zhen; Gao, Wenyuan

    2016-02-20

    Tongmai Yangxin (TMYX) Pill is a traditional Chinese patent medicine, composed of eleven Chinese medicinal herbs. It has been used to treat coronary heart disease for several decades. In this study, six male Sprague-Dawley rats were dosed orally with TMYX methanol extract, and a serum pharmacochemistry technique was used to screen absorbed bioactive compounds by UPLC/Q-TOF-MS. By comparing MS spectra to the published literature data, 40 bioactive components were identified. The results indicated that almost 45% of the absorbed compounds were from Radix Glycyrrhizae (GC). Subsequently, a reliable HPLC method was used to determine the concentrations of liquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid in rat plasma following oral administration of GC or the combination of GC and Ramulus Cinnamomi (GZ). The results showed that GZ enhanced the absorption of four bioactive components: liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid. The data demonstrate that herb combination in TMYX Pill exhibit a synergistic action. PMID:26771134

  4. Effect of different dispersing agents on the characteristics of Eudragit microspheres prepared by a solvent evaporation method.

    PubMed

    Horoz, B B; Kiliçarslan, M; Yüksel, N; Baykara, T

    2004-03-01

    Eudragit RS microspheres containing verapamil HCl for oral use were prepared using three different dispersing agents: aluminium tristearate, magnesium stearate and sucrose stearate, by a solvent evaporation method. The effects of the type and concentration of the dispersing agents and the inner phase polymer concentration on the size and T63.2%, (the time at which 63.2% of the drug is released) of microspheres were determined by multiple linear regression analysis. The morphology of microspheres was characterized by scanning electron microscopy. The surface of microspheres prepared with sucrose stearate was smoother and non-porous and the drug release from these microspheres was the fastest. When aluminium tristearate or magnesium stearate were used as dispersing agents, the particle size of microspheres became smaller. Increasing amounts of these two dispersing agents led to the accumulation of their free particles onto the surfaces of the microspheres. The drug release from the microspheres was slower than that of the microspheres from sucrose stearate depending on their hydrophobic structures. According to the results of the multiple linear regression analysis among the dispersing agents used, aluminium tristearate showed the best correlation between the examined input (dispersing agent and polymer concentrations) and output (T63.2%. and particle size) variables. PMID:15198430

  5. Ribozymes targeted to stearoyl-ACP delta9 desaturase mRNA produce heritable increases of stearic acid in transgenic maize leaves.

    PubMed Central

    Merlo, A O; Cowen, N; Delate, T; Edington, B; Folkerts, O; Hopkins, N; Lemeiux, C; Skokut, T; Smith, K; Woosley, A; Yang, Y; Young, S; Zwick, M

    1998-01-01

    Ribozymes are RNAs that can be designed to catalyze the specific cleavage or ligation of target RNAs. We have explored the possibility of using ribozymes in maize to downregulate the expression of the stearoyl-acyl carrier protein (Delta9) desaturase gene. Based on site accessibility and catalytic activity, several ribozyme constructs were designed and transformed into regenerable maize lines. One of these constructs, a multimer hammerhead ribozyme linked to a selectable marker gene, was shown to increase leaf stearate in two of 13 maize lines. There were concomitant decreases in Delta9 desaturase mRNA and protein. The plants with the altered stearate phenotype were shown to express ribozyme RNA. The ribozyme-mediated trait was heritable, as evidenced by stearate increases in the leaves of the R1 plants derived from a high-stearate line. The increase in stearate correlated with the presence of the ribozyme gene. A catalytically inactive version of this ribozyme did not produce any significant effect in transgenic maize. This is evidence that ribozymes can be used to modulate the expression of endogenous genes in maize. PMID:9761789

  6. Poly(ethylene glycol) hydroxystearate-based nanosized emulsions: effect of surfactant concentration on their formation and ability to solubilize quercetin.

    PubMed

    Dora, Cristiana L; Silva, Luis F C; Putaux, Jean-Luc; Nishiyama, Yoshiharu; Pignot-Paintrand, Isabelle; Borsali, Redouane; Lemos-Senna, Elenara

    2012-04-01

    Quercetin is a natural compound that has shown several biological activities. However, it displays poor water solubility and, therefore, low bioavailability. In this study, oil-in-water nanosized emulsions were obtained by the hot solvent diffusion method, using castor oil as oily phase and poly(ethylene glycol) (660)-12-hydroxystearate (PEG 660-stearate) and lecithin as surfactants. The effect of the PEG 660-stearate concentration on the droplet size of the nanosized emulsions and on the ability of these systems to load quercetin was investigated. Dynamic light scattering (DLS), transmission electron microscopy (TEM), cryo-TEM, and small-angle X-ray scattering (SAXS) were used to characterize the systems. We have demonstrated that a critical concentration of PEG 660-stearate (2.5 wt%) was needed to obtain colloidal dispersions displaying microemulsion characteristics. This colloidal dispersion, that was not optically birefringent, was constituted by a monodisperse population of 20 nm-large droplets, and exhibited excellent stability. Besides, this system was able to solubilize five times more quercetin than nanoemulsions prepared using 0.25 wt% PEG 660-stearate. SAXS results suggest that the spherical droplets have a core-shell structure. With regard to the hot solvent diffusion method, both diffusion of the solvent towards the aqueous phase and increase of the temperature above the phase inversion temperature (PIT) of PEG 660-stearate appeared to be required for obtaining clear and isotropic colloidal dispersions. PMID:22515071

  7. One-step spray-coating process for the fabrication of colorful superhydrophobic coatings with excellent corrosion resistance.

    PubMed

    Li, Jian; Wu, Runni; Jing, Zhijiao; Yan, Long; Zha, Fei; Lei, Ziqiang

    2015-10-01

    A simple method was used to generate colorful hydrophobic stearate particles via chemical reactions between inorganic salts and sodium stearate. Colored self-cleaning superhydrophobic coatings were prepared through a facile one-step spray-coating process by spraying the stearate particle suspensions onto stainless steel substrates. Furthermore, the colorful superhydrophobic coating maintains excellent chemical stability under both harsh acidic and alkaline circumstances. After being immersed in a 3.5 wt % NaCl aqueous solution for 1 month, the as-prepared coatings remained superhydrophobic; however, they lost their self-cleaning property with a sliding angle of about 46 ± 3°. The corrosion behavior of the superhydrophobic coatings on the Al substrate was characterized by the polarization curve and electrochemical impedance spectroscopy (EIS). The electrochemical corrosion test results indicated that the superhydrophobic coatings possessed excellent corrosion resistance, which could supply efficient and long-term preservation for the bare Al substrate. PMID:26365307

  8. Galenic approaches in troubleshooting of glibenclamide tablet adhesion in compression machine punches

    PubMed Central

    Boniatti, Janine; Pereira Cerqueira, Ana Lúcia; de Souza, Alexandre Carnevale; Drago Hoffmeister, Cristiane Rodrigues; da Costa, Maira Assis; Prado, Livia Deris; Tasso, Leandro; Antunes Rocha, Helvécio Vinícius

    2013-01-01

    This study aimed to examine the adhesion of glibenclamide 5 mg tablets to the tools of compression machines. This problem is not commonly reported in the literature, since it is considered as tacit knowledge. The starting point was the implementation of three technical alternatives: changing the parameters of compression, evaluating the humidity of the powder blend and the manufacturer of the lubricant magnesium stearate. The adhesion was directly related to the characteristics of magnesium stearate from different manufacturers, and the feasibility of evaluating powder flow characteristics by different techniques that are not routinely followed in various pharmaceutical companies. In vitro dissolution tests showed that the magnesium stearate manufacturer can influence on the dissolution profile of glibenclamide tablets. This study presented various aspects of tablet adhesion to compression machine punches. Troubleshooting approaches can be, most of times, conducted based on previous experience, or an experimental research needs to be implemented in order to have confident results. PMID:25473333

  9. Galenic approaches in troubleshooting of glibenclamide tablet adhesion in compression machine punches.

    PubMed

    Boniatti, Janine; Pereira Cerqueira, Ana Lúcia; de Souza, Alexandre Carnevale; Drago Hoffmeister, Cristiane Rodrigues; da Costa, Maira Assis; Prado, Livia Deris; Tasso, Leandro; Antunes Rocha, Helvécio Vinícius

    2014-11-01

    This study aimed to examine the adhesion of glibenclamide 5 mg tablets to the tools of compression machines. This problem is not commonly reported in the literature, since it is considered as tacit knowledge. The starting point was the implementation of three technical alternatives: changing the parameters of compression, evaluating the humidity of the powder blend and the manufacturer of the lubricant magnesium stearate. The adhesion was directly related to the characteristics of magnesium stearate from different manufacturers, and the feasibility of evaluating powder flow characteristics by different techniques that are not routinely followed in various pharmaceutical companies. In vitro dissolution tests showed that the magnesium stearate manufacturer can influence on the dissolution profile of glibenclamide tablets. This study presented various aspects of tablet adhesion to compression machine punches. Troubleshooting approaches can be, most of times, conducted based on previous experience, or an experimental research needs to be implemented in order to have confident results. PMID:25473333

  10. An investigation into the erosion behaviour of a high drug-load (85%) particulate system designed for an extended-release matrix tablet. Analysis of erosion kinetics in conjunction with variations in lubrication, porosity and compaction rate.

    PubMed

    Dürig, T; Venkatesh, G M; Fassihi, R

    1999-10-01

    The effects of the amounts of lubricants (magnesium stearate 0-5% and talc 0-3%) and changes in compaction rate and tablet porosity on the mechanism of drug release from high drug-load controlled-release theophylline tablets have been examined. Drug release was satisfactorily described by a surface-erosion model that takes into account the geometry of the tablet, differential radial and axial erosion rates, and the initial burst effect (r2 > 0.99 for all formulations). The axial and radial erosion rate constants were inversely proportional to the amount of magnesium stearate in the formulation (P < 0.0001). The most dramatic reductions in erosion rate occurred between 0 and 1% magnesium stearate content. For magnesium stearate concentrations > or =2.5% the ratio of radial to axial erosion rate constants was essentially constant at 3 (approx.); however, for formulations with magnesium stearate < or =1% the ratio tended toward unity. Reducing matrix porosity over the range 26 to 14% resulted in reduced erosion rates. However, a threshold of 17% (approx.) porosity was identified below which further reductions in porosity resulted in only incremental changes in release rates. The rate of erosion and drug release was insensitive to changes in machine speed over the range 20 to 100 rev min(-1). For highly loaded matrix tablets containing sparingly soluble drugs, such as theophylline, magnesium stearate at appropriate levels can modulate the erosion rate constants and act as an effective release-controlling excipient. Drug-release profiles are predictable and relatively robust in terms of changes in compaction rate and applied force routinely encountered in large-scale tablet manufacturing. PMID:10579678

  11. Intrinsically thermochromic fluorans.

    PubMed

    Azizian, Farid; Field, Amanda J; Heron, B Mark; Kilner, Colin

    2012-01-18

    A Suzuki coupling strategy has been employed to access a series of novel fluorans substituted with a phenolic moiety. These fluorans display good thermochromism in methyl stearate and obviate the need for traditional complex formulations containing acidic colour developers. PMID:22113189

  12. Omega-functionalized fatty acids, alcohols, and ethers via olefin metathesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyl 17-hydroxy stearate was converted to methyl octadec-16-enoate using copper sulfate adsorbed on silica gel. This compound, possessing unsaturation at the opposite end of the chain from the carboxylate, served as a useful substrate for the olefin metathesis reaction. As a result, several fatt...

  13. 40 CFR 180.910 - Inert ingredients used pre- and post-harvest; exemptions from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., conforming to 21 CFR 172.210 Coating agent Calcium silicate Solid diluent, carrier Calcium stearate Do. Carrageenan, conforming to 21 CFR 172.620 Minimum molecular weight (in amu): 100,000 Thickener Cetyl alcohol... surfactants Fatty acids, conforming to 21 CFR 172.860 Binder, defoaming agent, lubricant FD&C Blue No. 1...

  14. A spectrophotometric transesterification-based assay for lipases in organic solvent.

    PubMed

    Goujard, L; Villeneuve, P; Barea, B; Lecomte, J; Pina, M; Claude, S; Le Petit, J; Ferré, E

    2009-02-01

    A new method to evaluate lipase activities in nonaqueous conditions using vinyl ester absorbance at ultraviolet (UV) wavelengths is described. The model reaction is the transesterification between vinyl stearate and pentanol in hexane at 30 degrees C or in decane at 50 degrees C. The conversion of vinyl stearate into pentyl stearate is monitored through decreasing UV absorbance at 200 nm. Six commercial lipases were tested with this method, and results were compared with gas chromatography (GC) quantification and a classical spectrophotometric method using p-nitrophenyl palmitate. Results from the new spectrophotometric assay are similar both to results from GC quantification (R(2)=0.999) and to results from p-nitrophenyl palmitate (R(2)=0.989). The proposed method is able to evaluate both high activity from immobilized lipases such as immobilized Candida antarctica B lipase (3060 +/- 350 U g(-1)) and low activity from crude enzymatic extracts such as Carica papaya dried latex (0.1 +/- 0.04 U g(-1)). The method has also been used to measure kinetic parameters of C. antarctica B lipase for vinyl stearate and the correlation between its synthesis activity and its concentration. The method has also proved to be effective in studying the acyl selectivity of a lipase by comparing its activities with increasing chain lengths of vinyl esters. PMID:19013125

  15. Introduction to Studies in Granular Mixing

    ERIC Educational Resources Information Center

    Llusa, Marcos; Muzzio, Fernando

    2008-01-01

    This article describes a hands-on educational activity designed to introduce students (or industrial employees) in the pharmaceutical arena to some of the most common problems in the mixing of solids: Active Pharmaceutical Ingredient (API) and lubricant (i.e. magnesium stearate) homogenization, characterization of segregation tendencies, and…

  16. Oleochemical synthesis of an acid cleavable hydrophobe for surfactant use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The synthesis of a series of branched hydroxy stearates from commercially available methyl oleate and common organic acids is reported. A variety of different acids, with 3 to 8 carbon atoms, and also varying in their branching and functionality, were used. The kinetics of the ring opening reactio...

  17. 21 CFR 176.200 - Defoaming agents used in coatings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... glycol (400) esters of coconut oil fatty acids Polyethylene glycol (400) monooleate Polyethylene glycol... alcohol tert-Butyl alcohol Butyl stearate Castor oil, sulfated, ammonium, potassium, or sodium salt Cetyl... of total coating solids. Animal and vegetable fats and oils. Tall oil. Dimethylpolysiloxane...

  18. Synthesis of cyclic acetals (ketals) from oleochemicals using a solvent free method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have studied the reaction selectivities of acid catalyzed ring opening reactions of epoxidized methyl oleate (methyl 9,10-epoxy stearate; EMO), to form either acetal or branched ester products. We have produced: methyl 9-(2-butyl-2-methyl-5-octyl-1,3-dioxolan-4-yl) nonanoate (hexanone methyl st...

  19. Mutations in SACPD-C result in a range of elevated stearic acid concentration in soybean seed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean oil has a wide variety of uses, and stearic acid, which is a relatively minor component of soybean oil is increasingly desired for both industrial and food applications. New soybean mutants containing high levels of the saturated fatty acid stearate in seeds were recently identified from a c...

  20. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using an inorganic particle matrix for small molecule analysis

    PubMed

    Kinumi; Saisu; Takayama; Niwa

    2000-03-01

    Fine metal or metal oxide powder as an alternative to conventional organic matrices in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been utilized successfully for lower molecular mass analytes, poly(ethylene glycol) 200 (PEG 200) and methyl stearate. Eleven kinds of particle, Al, Mn, Mo, Si, Sn, SnO2, TiO2, W, WO3, Zn and ZnO, were evaluated. The analyte was mixed with a metal or metal oxide powder (inorganic matrix) with particle diameter of tens of micrometers and liquid dispersant, followed by application to the sample target. Using a commercial MALDI-TOFMS instrument equipped with an internal 337 nm pulsed nitrogen laser, the analytes, PEG 200 and methyl stearate, were ionized as the alkali metal ion adducted molecules [M+Na]+ or [M+K]+ when the inorganic matrices Mn, Mo, Si, Sn, TiO2, W, WO3, Zn or ZnO were used. In the case of an Al matrix, PEG 200 was ionized as [M+K]+, whereas methyl stearate was ionized as [M+H]+ and [M+Al]+. These particles have potential as the matrix for MALDI. During our examination, however, only SnO2 particles did not ionize either PEG 200 or methyl stearate. Based on our protocol, when TiO2 powder was suspended with liquid paraffin, PEG 200 and methyl stearate gave their MALDI-TOF mass spectra with the lowest background noise and highest intensity. TiO2 powder seemed to be a broad potential matrix for low molecular mass polar or non-polar analytes. The results suggested that bulk particles caused rapid heating/vaporization processes and ionized analyte molecules under irradiation with a pulsed UV laser. The present method can be readily applied to obtain the low background noise MALDI-TOF mass spectra of small-sized compounds. PMID:10767772

  1. Preparation and evaluation of a non-viral gene vector for SiRNA: Multifunctional envelope-type nano device (.).

    PubMed

    Zhang, Ying; Wei, Haitian; Xu, Lisa; Yan, Guowen; Ma, Chao; Yu, Miao; Wei, Chen; Sun, Yong

    2016-08-01

    We prepared and evaluated a multifunctional envelope-type nano device (MEND) as a liver-targeting and long-circulation carrier for SiRNA. The polymer GA-PEG-Pp-DOPE was synthesized by modifying polyethylene glycol (PEG) with glycyrrhetinic acid (GA), peptide (Pp), and dioleoyl phosphoethanolamine (DOPE). The Pp is a substrate of matrix metalloproteinase 2. MEND was prepared with GA-PEG-Pp-DOPE and cationic phospholipids by the filming-rehydration method, and the orthogonal test was applied to optimize the prescription. The results of the biological evaluation results suggest that MEND is a promising delivery system for SiRNA. PMID:25813567

  2. Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L.

    PubMed

    Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A

    1993-01-01

    Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid. PMID:8451033

  3. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    PubMed Central

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  4. Bifunctional graphene/γ-Fe₂O₃ hybrid aerogels with double nanocrystalline networks for enzyme immobilization.

    PubMed

    Chen, Liang; Wei, Bin; Zhang, Xuetong; Li, Chun

    2013-07-01

    Highly porous hosting materials with conducting (favorable to electron transfer) and magnetic (favorable to product separation) bicontinuous networks should possess great potentials for immobilization of various enzymes in the field of biocatalytic engineering, but the synthesis of such materials is still a great challenge. Herein, bifunctional graphene/γ-Fe2 O3 hybrid aerogels with quite low density (30-65 mg cm(-3) ), large specific surface area (270-414 m(2) g(-1) ), high electrical conductivity (0.5-5 × 10(-2) S m(-1) ), and superior saturation magnetization (23-54 emu g(-1) ) are fabricated. Single networks of either graphene aerogels or γ-Fe2 O3 aerogels are obtained by etching of the hybrid aerogels with acid solution or calcining of the hybrid aerogels in air, indicative of the double networks of the as-synthesized graphene/γ-Fe2 O3 hybrid aerogels for the first time. The resulting bifunctional aerogels are used to immobilize β-glucuronidase for biocatalytic transformation of glycyrrhizin into glycyrrhetinic acid monoglucuronide or glycyrrhetinic acid, with high biocatalytic activity and definite repeatability. PMID:23423944

  5. Formulation of carbenoxolone for delivery to the skin.

    PubMed

    Hirata, Kazumasa; Helal, Fouad; Hadgraft, Jonathan; Lane, Majella E

    2013-05-20

    Carbenoxolone (CEX), a semi-synthetic derivative of glycyrrhetinic acid, has previously been used as a disodium salt for the management of dyspepsia and peptic ulcer because of its anti-inflammatory properties. Although glycyrrhetinic acid is available in pharmaceutical and personal care products for skin care, the topical use of the free acid form of CEX, has not previously been reported. In this work we investigated the percutaneous penetration of CEX. Solubility and permeability studies were conducted using a range of solvents or skin permeation enhancers (SPEs) commonly used for skin delivery. Binary combinations of dimethyl isosorbide (DMI) and Transcutol™ (TC) with isopropyl myristate (IPM) were effective in promoting skin permeation of CEX although individual solvents were not. Alternative fatty acid esters to IPM were subsequently investigated with the most promising formulation consisting of TC and propylene glycol laurate (PGL). Interestingly, propylene glycol monolaurate (PGML) did not demonstrate comparable efficacy when combined with TC. A ternary formulation consisting of TC, PGL and IPM demonstrated the best permeation enhancement of CEX compared with all other vehicles. The findings confirm (i) the feasibility of promoting CEX penetration across the skin (ii) the synergistic effect of combinations of solvents and SPEs on dermal and transdermal delivery (iii) the necessity for more fundamental studies to explain the differential effects of fatty acid esters on the skin barrier. PMID:23545397

  6. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches.

    PubMed

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  7. Pseudohyperaldosteronism: pathogenetic mechanisms.

    PubMed

    Armanini, Decio; Calò, Lorenzo; Semplicini, Andrea

    2003-06-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of plasma renin activity and aldosterone. Pseudohyperaldosteronism can be due to a direct mineralocorticoid effect, as with desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone, estrogens, and the ingestion of high amounts of glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the enzyme that converts cortisol into cortisone, at the level of epithelial target tissues of aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe Cushing's syndrome and chronic therapy with some corticosteroids. Recently, an activating mutation of the mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the sodium channels. PMID:12892318

  8. 11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse

    PubMed Central

    Sanna, P P; Kawamura, T; Chen, J; Koob, G F; Roberts, A J; Vendruscolo, L F; Repunte-Canonigo, V

    2016-01-01

    The identification of new and more effective treatments for alcohol abuse remains a priority. Alcohol intake activates glucocorticoids, which have a key role in alcohol's reinforcing properties. Glucocorticoid effects are modulated in part by the activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) acting as pre-receptors. Here, we tested the effects on alcohol intake of the 11β-HSD inhibitor carbenoxolone (CBX, 18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively used in the clinic for the treatment of gastritis and peptic ulcer and is active on both 11β-HSD1 and 11β-HSD2 isoforms. We observed that CBX reduces both baseline and excessive drinking in rats and mice. The CBX diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which we found to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors may be a promising new class of candidate alcohol abuse medications, and existing 11β-HSD inhibitor drugs may be potentially re-purposed for alcohol abuse treatment. PMID:26978742

  9. Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species

    PubMed Central

    Farag, Mohamed A.; Porzel, Andrea; Wessjohann, Ludger A.

    2014-01-01

    Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and as sweetener in the food industry. This species contains a myriad of phytochemicals including the major saponin glycoside glycyrrhizin (G) of Glycyrrhetinic acid (GA) aglycone. In this study, 2D-ROESY NMR technique was successfully applied for distinguishing 18α and 18β glycyrrhetinic acid (GA). ROESY spectra acquired from G. glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata crude extracts revealed the presence of G in its β-form. Anti-inflammatory activity of four Glycyrrhiza species, G, glabra, G. uralensis, G. inflata, and G. echinata roots was assessed against COX-1 inhibition revealing that phenolics rather than glycyrrhizin are biologically active in this assay. G. inflata exhibits a strong cytotoxic effect against PC3 and HT29 cells lines, whereas other species are inactive. This study presents an effective NMR method for G isomer assignment in licorice extracts that does not require any preliminary chromatography or any other purification step. PMID:25685548

  10. Phase behavior of microemulsion systems studied by positron annihilation techniques

    SciTech Connect

    Serrano, J.; Reynoso, R.; Lopez, R.; Olea, O.; Fucugauchi, L.A.

    1983-02-17

    The positron annihilation technique was applied to the study of phase behavior of sodium stearate (or oleate)-alcohol-oil-water microemulsion systems. The positron annihilation parameters revealed a dependence of the water/oil ratio at which microemulsion formation occurs on the hydrocarbon chain length of both alcohol cosurfactant and solvent as well as surfactant concentration. Dynamic laser light scattering has been utilized for substantiating the phase transitions determined in the different microemulsion systems by positron annihilation. The difference in the behavior between saturated and unsaturated surfactants is the most remarkable result of the investigation. Thus, replacing sodium stearate by sodium oleate in the surfactant-1-hexanol-isooctane systems obviated microemulsion formation. This behavior has been rationalized by considering packing and kink presence in microemulsion formation. 26 references.

  11. Adsorptive bubble separation of zinc and cadmium cations in presence of ferric and aluminum hydroxides.

    PubMed

    Jurkiewicz, Kazimierz

    2005-06-15

    The adsorptive bubble separation of zinc and cadmium cations from solution in the presence of ferric and aluminum hydroxides was carried out by means of Tween 80 (nonionic surfactant), and sodium laurate and stearate (anionic surfactants). The mechanism of metal removal is different depending on the nature of the surfactant used. The removal of zinc cations by adsorbing colloid flotation is higher than that of cadmium cations. It increases with increases in the amount of hydroxide precipitate and the concentration of Tween 80. The removal of zinc cations by ion flotation is lower than that of cadmium cations. It does not change with increases in the hydroxide amount. It increases, however, with increased sodium laurate or stearate concentration. Both separation methods turned out to be helpful for studying both the solution's structure and the interactions at the solution-solid interface. PMID:15897071

  12. Compatibility between active components of a commercial drug.

    PubMed

    Rodante, Fabrizio; Vecchio, Stefano; Catalani, Giovanni; Tomassetti, Mauro

    2002-10-01

    A thermal and a kinetic analysis on the decomposition processes of a commercial drug named diamplicil (AD), obtained by an antibiotic combination of ampicillin (A) and dicloxacillin (D), have been carried out to find their thermal stability. The DSC/TG curves of this commercial drug were compared with those of its active components and an excipient, the magnesium stearate (M). Kinetic study was carried out using both isothermal and dynamic TG curves. Decomposition mechanisms for both active components and commercial drug tested were not found. The kinetic data obtained by the non-isothermal isoconversional method showed that D component causes a decrease of the kinetic stability of the active A component. Additive magnesium stearate does not decrease the stability of the two components. Moreover, storage time values at room temperature were calculated. PMID:12420879

  13. EPR investigation of some gamma-irradiated excipients

    NASA Astrophysics Data System (ADS)

    Aleksieva, Katerina; Yordanov, Nicola D.

    2012-09-01

    The results of electron paramagnetic resonance (EPR) studies on some excipients: lactose, microcrystalline cellulose (avicel), starch, dioxosilane (aerosil), talc and magnesium stearate before and after gamma-irradiation are reported. Before irradiation, all samples are EPR silent except talc. After gamma-irradiation, they show complex spectra except magnesium stearate, which is EPR silent. Studies show the influence of gamma-irradiation on EPR spectra and stability of gamma-induced radicals. Analysis of the EPR spectrum of gamma-irradiated talc shows that this material is radiation insensitive. Only lactose forms stable-free radicals upon gamma sterilization and can be used for identification of radiation processing for a long time period thereafter.

  14. Saturated Free Fatty Acids Induce Cholangiocyte Lipoapoptosis

    PubMed Central

    Natarajan, Sathish Kumar; Ingham, Sally A.; Mohr, Ashley M.; Wehrkamp, Cody J.; Ray, Anuttoma; Roy, Sohini; Cazanave, Sophie C.; Phillippi, Mary Anne; Mott, Justin L.

    2015-01-01

    Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation of the proapoptotic BH3-containing protein, PUMA. In addition, palmitate-induced cholangiocyte lipoapoptosis involved a time-dependent increase in the nuclear localization of forkhead family of transcription factor 3 (FoxO3). We show evidence for posttranslational modification of FoxO3, including early (6 hours) deacetylation and dephosphorylation that coincide with localization of FoxO3 in the nuclear compartment. By 16 hours, nuclear FoxO3 is both phosphorylated and acetylated. Knockdown studies confirmed that FoxO3 and its downstream target, PUMA, were critical for palmitate- and stearate-induced cholangiocyte lipoapoptosis. Interestingly, cultured cholangiocyte-derived cells did not accumulate appreciable amounts of neutral lipid upon FFA treatment. Conclusion Our data show that the saturated FFAs palmitate and stearate induced cholangiocyte lipoapoptosis by way of caspase activation, nuclear translocation of FoxO3, and increased proapoptotic PUMA expression. These results suggest that cholangiocyte injury may occur through lipoapoptosis in NAFLD and nonalcoholic steatohepatitis patients. PMID:24753158

  15. Au/Cr-ZnO-Ni structured metal-insulator-metal diode fabrication using Langmuir-Blodgett technique for infrared sensing

    NASA Astrophysics Data System (ADS)

    Azad, Ibrahim; Ram, Manoj K.; Goswami, D. Yogi; Stefanakos, Elias

    2016-05-01

    The thin nanolayer film of ZnO was synthesized through Langmuir-Blodgett (LB) organic precursor film. The zinc stearate monolayer was formed at air-water interface using zinc acetate as a subphase. The zinc stearate monolayers were deposited on silicon (Si), glass, and gold (Au)/chromium (Cr) plated Silicon (Si) substrates using LB technique. Later, the zinc stearate multilayers LB films on various substrates were annealed at two different temperatures (300oC and 550oC) for the fabrication of zinc oxide (ZnO) nanolayer film. The zinc stearate monolayers as well zinc oxide (ZnO) nanolayer films were characterized using atomic force microscopy (AFM) and X-ray diffraction techniques. The X-ray diffraction measurement has shown the hexagonal wurtzite structure of the ZnO nanolayer on the substrate. The average surface roughness was estimated to be 1.076 nm using AFM technique. The metal-insulator-metal (MIM) diode structure was realized by sandwiching ZnO nanolayer film between thin layer of Gold (Au)/Chromium (Cr) and Nickel (Ni) on silicon substrates. The electron tunneling conduction mechanism is understood through the current-voltage (I-V) characteristics of MIM diode. The highest measured sensitivity magnitude of 20 in inverse of voltage (V-1) with rectification ratio of nearly 10 at +/-400 mV in MIM diode is an indicative of its potential application in infrared sensing applications. However, the thin film of ZnO synthesized using LB film as an insulating layer in metal-insulator-metal diode structure was studied for the first time.

  16. Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells*

    PubMed Central

    Yee, Jennifer K.; Mao, Catherine S.; Hummel, Heidi S.; Lim, Shu; Sugano, Sharon; Rehan, Virender K.; Xiao, Gary; Lee, Wai-Nang Paul

    2008-01-01

    Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the conversion of stearate (18:0) to oleate (18:1n-9) and of palmitate (16:0) to palmitoleate (16:1), which are key steps in triglyceride synthesis in the fatty acid metabolic network. This study investigated the role of SCD1 in fatty acid metabolism in HepG2 cells using SCD1 inhibitors and stable isotope tracers. HepG2 cells were cultured with [U-13C]stearate, [U-13C]palmitate, or [1,2-13C]acetate and (1) DMSO, (2) compound CGX0168 or CGX0290, or (3) trans-10,cis-12 conjugated linoleic acid (CLA). 13C incorporation into fatty acids was determined by GC-MS and desaturation indices calculated from the respective ion chromatograms. FAS, SCD1, peroxisome proliferator-activated receptor α, and peroxisome proliferator-activated receptor γ mRNA levels were assessed by semiquantitative RT-PCR. The addition of CGX0168 and CGX0290 decreased the stearate and palmitate desaturation indices in HepG2 cells. CLA led to a decrease in the desaturation of stearate only, but not palmitate. Comparison of desaturation indices based on isotope enrichment ratios differed, depending on the origin of saturated fatty acid. SCD1 gene expression was not affected in any group. In conclusion, the differential effects of SCD1 inhibitors and CLA on SCD1 activity combined with the dependence of desaturation indices on the source of saturated fatty acid strongly support the compartmentalization of desaturation systems. The effects of SCD1 inhibition on fatty acid composition in HepG2 cells occurred through changes in the dynamics of the fatty acid metabolic network and not through transcriptional regulatory mechanisms. PMID:18599738

  17. Extinguishing agent for combustible metal fires

    DOEpatents

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

    A low chloride extinguishing agent for combustible metal fires comprising from substantially 75 to substantially 94 weight percent of sodium carbonate as the basic fire extinguishing material, from substantially 1 to substantially 5 weight percent of a water-repellent agent such as a metal stearate, from substantially 2 to substantially 10 weight percent of a flow promoting agent such as attapulgus clay, and from substantially 3 to substantially 15 weight percent of a polyamide resin as a crusting agent.

  18. Microencapsulation of beta-galactosidase with Eudragit L-100.

    PubMed

    Squillante, E; Morshed, G; Bagchi, S; Mehta, K A

    2003-01-01

    Microcapsules containing beta-galactosidase (lactase) were prepared by solvent evaporation using the pH sensitive polymer, Eudragit L-100. Formulations were prepared using various polymer-enzyme ratios with total solids content of the internal phase using sucrose stearate as a droplet stabilizer. Particle size distributions were invariant to relative proportion of ingredients but were dependent on stirring conditions. Although sucrose stearate had no effect on particle size distribution, release rate or encapsulation efficiency, its presence at a minimum 2% level was necessary to ensure intact microcapsules. Encapsulation efficiencies were higher for formulations prepared with 15% compared to 10% total solid content. DSC results revealed an interaction between encapsulated Eudragit L-100-enzyme-sucrose stearate vs their physical mixtures. The enzyme activities of the freshly prepared product vs those stored under stressed condition (40 degrees C and 75% RH) were 68 and 40% of their pre-processing activity, respectively. In vitro dissolution showed no enzyme release at 1 h in acidic media but 80% of the lactase was released from the microcapsules over 2.5 h in pH 6.8 media, thus establishing the feasibility of lactase microencapsulation to retard enzyme release in an acidic environment and ensuring release at intestinal pH. PMID:12554371

  19. Mechanical properties of potato starch modified by moisture content and addition of lubricant

    NASA Astrophysics Data System (ADS)

    Stasiak, Mateusz; Molenda, Marek; Horabik, Józef; Mueller, Peter; Opaliński, Ireneusz

    2014-10-01

    Laboratory testing was conducted to deliver a set of characteristics of structure and mechanical properties of pure starch and starch with an addition of a lubricant - magnesium stearate. Considerable influence of moisture content of potato starch was found in the case of density, parameters of internal friction, coefficients of wall friction and flowability. Elasticity was found to be strongly influenced by water content of the material. Addition of magnesium stearate affected density and parameters of flowability, internal friction and elasticity. Bulk density increased from 604 to 774 kg m-3 with decrease in moisture content of potato starch from 17 to for 6%. Addition of magnesium stearate resulted in approximately 10% decrease in bulk density. Angle of internal friction obtained for 10 kPa of consolidation stress decreased from 33 to 24º with increase in moisture content, and to approximately 22º with addition of the lubricant. With an increase of moisture content from 6 to 18% and with addition of the lubricant, the modulus of elasticity during loading decreased from approximately 1.0 to 0.1 MPa. Modulus of elasticity during unloading was found in the range from 19 to 42 MPa and increased with increase of moisture content and amount of lubricant.

  20. Determination of tackiness of chitosan film-coated pellets exploiting minimum fluidization velocity.

    PubMed

    Fernández Cervera, M; Heinämäki, J; Räsänen, E; Antikainen, O; Nieto, O M; Iraizoz Colarte, A; Yliruusi, J

    2004-08-20

    The tackiness of aqueous chitosan film coatings and effects of anti-sticking agents on sticking tendency, were evaluated. A novel rapid method exploiting minimum fluidization velocity to determine tackiness was introduced and tested. The pressure difference over the miniaturized fluidized-bed was precisely recorded as a function of velocity of fluidization air. High molecular weight chitosan plasticized with glycerol was used as a film-forming agent. Magnesium stearate, titanium dioxide, colloidal silicon dioxide and glyceryl-1-monostearate (GMS) were studied as anti-sticking agents. Film coatings were performed in a miniaturized top-spray coater. The incorporation of anti-sticking agents led to a clear decrease in tackiness of the chitosan films, and magnesium stearate and GMS were shown the most effective. Film-coated pellets containing magnesium stearate and GMS as an anti-sticking agent were very easily fluidized (showing very low values of minimum fluidization velocity) and were thus classified as the best flowing and the least sticking samples. Both these additives were found anti-sticking agents of choice for aqueous chitosan film coatings. Determination of the experimental minimum fluidization velocity in a fluidized bed, is a useful and sensitive method of measuring the tackiness tendency of film-coated pellets. PMID:15288349

  1. Comparison of properties of tablets and energy profile of compaction of two spray-dried lactoses.

    PubMed

    Muzíková, Jitka; Sináglová, Pavla

    2013-01-01

    The paper compared two spray-dried lactoses Flowlac 100 and SuperTab 14SD from the standpoint of tensile strength and disintegration time of tablets, the effect of an addition of the lubricant magnesium stearate and silicified microcrystalline cellulose on these properties, and also from the standpoint of the energy profile of compression. The comparison of the values was performed at the compression force of 15 kN. The strength of tablets was higher in the case of SuperTab 14SD, an increase in the concentration of magnesium stearate did not decrease tablet strength. Prosolv SMCC 90 increased the strength of tablets and made it equal for both lactoses, but it also increased the sensitivity to the added lubricant. The disintegration time of tablets was shorter in the case of SuperTab 14SD, an increased concentration of magnesium stearate prolonged it, and an addition of Prosolv SMCC 90 shortened it and made it equal for both lactoses. From the energy standpoint, the maximal energy was higher in the case of SuperTab 14SD, an addition of Prosolv SMCC 90 increased it and again made it equal for both lactoses. The differences in the values of the maximal energy were primarily due to the values of the energy for friction and the energy accumulated by the tablet after compression, and there was no marked difference in the values of the energy of decompression. SuperTab 14SD showed a higher plasticity than Flowlac 100. PMID:23610968

  2. 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.

  3. Adsorption of short-chain organic acids onto nearshore marine sediments

    NASA Astrophysics Data System (ADS)

    Sansone, Francis J.; Andrews, Christine C.; Okamoto, Mauri Y.

    1987-07-01

    The adsorption of acetate, butyrate, lactate, and stearate was measured using a clastic mud from Cape Lookout Bight N.C. (CLB), a lateritic muddy sand from Kahana Stream, Oahu, Hawaii (KS), and a fine carbonate sand from Waimanalo Beach, Oahu, (WB). Partition coefficients ( Kd, moles adsorbed per g of solid phase/moles dissolved per ml of porewater) ranged from 10 2.3 to ≤10 -3.0, and displayed the following trends: CLB > KS > WB, and stearate > acetate ˜- butyrate > lactate. The percent adsorption of the sediment organic acid pools showed similar trends: stearate, 99%; acetate, 9-23%; butyrate, 5-23%; lactate, ≤0.2-7%. These results reflected the relatively nonpolar nature of the sand surfaces in WB and KS sediments, and the polarities of the organic acids. Kd was approximately constant for each organic acid-sediment combination over a dissolved organic acid concentration range of 10 7, using concentrations between 1M and 10 -14 M. This constancy over a wide porewater concentration range suggested that adsorption was not limited by the availability of surface adsorption sites.

  4. Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

    PubMed

    Jedinger, N; Schrank, S; Mohr, S; Feichtinger, A; Khinast, J; Roblegg, E

    2015-05-01

    The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's. PMID:25733499

  5. VB12-coated Gel-Core-SLN containing insulin: Another way to improve oral absorption.

    PubMed

    He, Haibing; Wang, Puxiu; Cai, Cuifang; Yang, Rui; Tang, Xing

    2015-09-30

    To improve the oral absorption of insulin, a novel carrier of Vitamin B12 (VB12) gel core solid lipid nanopaticles (Gel-Core-SLN, GCSLN) was designed with a gel core, lipid matrix and VB12-coated surface. VB12-stearate was synthesized and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Sol-gel conversion following ultrasonic heating and double emulsion technology were combined to implant the insulin-containing gel into solid lipid nanoparticles (SLN). The influence of the mode of administration, food, the amount of VB12-stearate and the particle size on the oral absorption of insulin incorporated in the VB12-GCSLN was investigated. The determined partition coefficient (LogP) of VB12-stearate in a dichloromethane (DCM)-water system was 3.4. This new structure of VB12-GCSLN had higher insulin encapsulation efficiency (EE) of 55.9%, a lower burst release of less than 10% in the first 2h. In vivo studies demonstrated that stronger absorption of insulin with a relative pharmacological availability (PA) of 9.31% compared with the normal insulin-loaded SLN and GCSLN and fairly stable blood glucose levels up to 12h were maintained without any sharp fluctuations. This study suggests that VB12-GCSLN containing insulin appears to be a promising nano carrier for oral delivery of biomacromolecules with relatively high pharmacological availability. PMID:26253378

  6. Mutations in SACPD-C Result in a Range of Elevated Stearic Acid Concentration in Soybean Seed

    PubMed Central

    Carrero-Colón, Militza; Abshire, Nathan; Sweeney, Daniel; Gaskin, Erik; Hudson, Karen

    2014-01-01

    Soybean oil has a wide variety of uses, and stearic acid, which is a relatively minor component of soybean oil is increasingly desired for both industrial and food applications. New soybean mutants containing high levels of the saturated fatty acid stearate in seeds were recently identified from a chemically mutagenized population. Six mutants ranged in stearate content from 6–14% stearic acid, which is 1.5 to 3 times the levels contained in wild-type seed of the Williams 82 cultivar. Candidate gene sequencing revealed that all of these lines carried amino acid substitutions in the gene encoding the delta-9-stearoyl-acyl-carrier protein desaturase enzyme (SACPD-C) required for the conversion of stearic acid to oleic acid. Five of these missense mutations were in highly conserved residues clustered around the predicted di-iron center of the SACPD-C enzyme. Co-segregation analysis demonstrated a positive association of the elevated stearate trait with the SACPD-C mutation for three populations. These missense mutations may provide additional alleles that may be used in the development of new soybean cultivars with increased levels of stearic acid. PMID:24846334

  7. Biodegradable polymers derived from renewable resources: Highly branched copolymers of itaconic anhydride

    NASA Astrophysics Data System (ADS)

    Wallach, Joshua Andrew

    In an effort to design cyclic anhydride containing polymers that are derived from renewable resources and have biodegradable characteristics, three copolymer systems using itaconic anhydride have been studied. Two of the systems were copolymers with stearate based monomers; vinyl stearate and stearyl methacrylate, while the third was a copolymer with a methacrylate terminated poly (lactic acid) (PLA) macromonomer. For the stearate systems, stearyl methacrylate showed good copolymerization with equal conversions for both monomers. On the other hand vinyl stearate did not show as good results due to its decreased reactivity, which resulted in a copolymer highly enriched in itaconic anhydride with significant amounts of unreacted vinyl stearate under all copolymer compositions. These differing results were confirmed through analysis of reactivity ratios showing a results that are more favorable for copolymerization for the methacrylate system. Copolymers from both systems showed single melting transitions in a precarious range of 45--50°C arising from the stearyl side groups, though after quenching from the melt this shifted to below room temperature. Anhydride retention was confirmed through structural analysis. Similar to the stearyl methacrylate system, methacrylate terminated PLA macromonomers were copolymerized with itaconic anhydride. PLA's acceptance as a biodegradable material derived from renewable resources, make it a viable choice, with which to design anhydride containing copolymers. Good copolymerization was shown for all compositions studied with retention of the anhydride, though at high itaconic anhydride concentrations conversions were reduced significantly. Copolymers showed glass transition temperatures ranging from 32°C for 85 mole % PLA macromonomer to 73°C for 85 mole % itaconic anhydride. An effort to produce PLA macromonomers through a process of chemical recycling commercial PLA was also undertaken. Promising results were obtained showing

  8. Pharmacokinetics of Maxing Shigan decoction in normal rats and RSV pneumonia model rats by HPLC-MS/MS.

    PubMed

    Jiang, Li; Gao, Meng; Qu, Fei; Li, Hui-lan; Yu, Lan-bin; Rao, Yi; Wang, Yue-sheng; Xu, Guo-liang

    2015-07-01

    To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL

  9. Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

    PubMed Central

    Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

    2014-01-01

    Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

  10. Effects of glycyrrhizin on UVB-irradiated melanoma cells.

    PubMed

    Rossi, Tiziana; Benassi, Luisa; Magnoni, Cristina; Ruberto, Antonio Ippazio; Coppi, Andrea; Baggio, Giosué

    2005-01-01

    It is known that liquorice root is rich in compounds which exert several pharmacological actions. In the present study, we evaluated the effect of glycyrrhizin (the main constituent of liquorice root) and of its metabolite aglycone, 18beta-glycyrrhetinic acid, on UVB-irradiated human melanoma cells: SKMEL-2 from metastatic tissue and SKMEL-28 from primary malignant melanoma. Tests performed (Trypan blue exclusion test, MTT and Western blot) showed that glycyrrhizin is not toxic for both types of cells. In SKMEL-28 cells, Bcl-2 expression was low after UVB irradiation, but it was increased when treated with glycyrrhizin. On the contrary, in the SKMEL-2 cell culture, Bcl-2 expression was not modified by the substances under study. The results show that glycyrrhizin treatment might offer protection from the damage induced in humans by UVB radiation, while it seems to be ineffective on metastatic cells. Further studies must be performed to understand the mechanism of the protective effect. PMID:15796192

  11. Dual-function fluorescent probe for cancer imaging and therapy.

    PubMed

    Cui, Hongjing; Wang, Ran; Zhou, Ying; Shu, Chang; Song, Fengjuan; Zhong, Wenying

    2016-05-01

    To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26387677

  12. Incorporation of a Michael acceptor enhances the antitumor activity of triterpenoic acids.

    PubMed

    Heller, Lucie; Schwarz, Stefan; Perl, Vincent; Köwitsch, Alexander; Siewert, Bianka; Csuk, René

    2015-08-28

    Finding and developing drugs for the treatment of cancer has been challenging scientists for many decades, and using compounds of natural origin represents one of several strategies. Triterpenoic acids are a very promising class of secondary metabolites being able to induce apoptosis while their cytotoxicity is low. Therefore, derivatizations have to be conducted to improve cytotoxicity while retaining their ability to induce programmed cell death. The incorporation of a Michael acceptor into molecules resulted very often in drugs of improved cytotoxicity. Thus, in this study we synthesized and evaluated several Michael acceptor substituted compounds derived from glycyrrhetinic, ursolic, oleanolic and platanic acid. The influence of the presence of such a functional group onto the cytotoxicity was investigated in colorimetric sulforhodamine B assays employing several human cancer cell lines. EC50 values in the single-digit micromolar range were measured. Thus, the incorporation of a Michael acceptor unit into triterpenoic acids enhances the cytotoxicity of these compounds significantly. PMID:26177446

  13. Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium.

    PubMed

    Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2004-08-15

    Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration-response curves were defined for the effects of heptanol, 18alpha-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n= 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n= 43) or 30 min (n= 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18alpha-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

  14. Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium

    PubMed Central

    Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2004-01-01

    Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration–response curves were defined for the effects of heptanol, 18α-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n = 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n = 43) or 30 min (n = 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18α-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

  15. Protective effect of gap junction uncouplers given during hypoxia against reoxygenation injury in isolated rat hearts.

    PubMed

    Rodríguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

    2006-02-01

    It has been shown that cell-to-cell chemical coupling may persist during severe myocardial hypoxia or ischemia. We aimed to analyze the effects of different, chemically unrelated gap junction uncouplers on the progression of ischemic injury in hypoxic myocardium. First, we analyzed the effects of heptanol, 18alpha-glycyrrhetinic acid, and palmitoleic acid on intracellular Ca2+ concentration during simulated hypoxia (2 mM NaCN) in isolated cardiomyocytes. Next, we analyzed their effects on developed and diastolic tension and electrical impedance in 47 isolated rat hearts submitted to 40 min of hypoxia and reoxygenation. All treatments were applied only during the hypoxic period. Cell injury was determined by lactate dehydrogenase (LDH) release. Heptanol, but not 18alpha-glycyrrhetinic acid nor palmitoleic acid, attenuated the increase in cytosolic Ca2+ concentration induced by simulated ischemia in cardiomyocytes and delayed rigor development (rigor onset at 7.31 +/- 0.71 min in controls vs. 14.76 +/- 1.44 in heptanol-treated hearts, P < 0.001) and the onset of the marked changes in electrical impedance (tissue resistivity: 4.02 +/- 0.29 vs. 7.75 +/- 1.84 min, P = 0.016) in hypoxic rat hearts. LDH release from hypoxic hearts was minimal and was not significantly modified by drugs. However, all gap junction uncouplers, given during hypoxia, attenuated LDH release during subsequent reoxygenation. Dose-response analysis showed that increasing heptanol concentration beyond the level associated with maximal effects on cell coupling resulted in further protection against hypoxic injury. In conclusion, gap junction uncoupling during hypoxia has a protective effect on cell death occurring upon subsequent reoxygenation, and heptanol has, in addition, a marked protective effect independent of its uncoupling actions. PMID:16183732

  16. [The interactions between natural products and OATP1B1].

    PubMed

    Shi, Mei-zhi; Liu, Yu; Bian, Jia-lin; Jin, Meng; Gui, Chun-shan

    2015-07-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use. PMID:26552146

  17. Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43

    PubMed Central

    ZHANG, XUMIN; WANG, XIAODONG; ZHOU, XIAOHUI; MA, XIAOYE; YAO, YIAN; LIU, XUEBO

    2016-01-01

    The current study aimed to investigate the relevance of the gap junction protein connexin Cx43 in coronary artery smooth muscle cell (SMC) heterogeneity and coronary artery restenosis. SMCs were isolated from the coronary artery of 3-month-old pigs using enzymatic digestion. Two distinct SMC populations were isolated: Rhomboid (R) and spindle-shaped (S) cells. S-SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills-and valleys'' growth pattern; R-SMCs displayed increased proliferation rates, growing as mono- or multi-layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet-derived growth factor (PDGF)-BB with or without the gap junction blocker 18α-glycyrrhetinic acid. Stent-induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R- and S-SMCs. Cx40 was the most abundant Cx in S-SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R-SMCs. Notably, PDGF-BB converted S-SMCs to R-SMCs, with increased Cx43 expression, while 18α-glycyrrhetinic acid inhibited the PDGF-BB-induced phenotypic alterations in S-SMCs. Additionally, restenosis was confirmed in pigs 1-month subsequent to stent placement. R-SMCs were the major cell population isolated from stent-induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention. PMID:27175888

  18. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo.

    PubMed

    Véliz, Loreto P; González, Francisco G; Duling, Brian R; Sáez, Juan C; Boric, Mauricio P

    2008-09-01

    To assess the hypothesis that gap junctions (GJs) participate on leukocyte-endothelium interactions in the inflammatory response, we compared leukocyte adhesion and transmigration elicited by cytokine stimulation in the presence or absence of GJ blockers in the hamster cheek pouch and also in the cremaster muscle of wild-type (WT) and endothelium-specific connexin 43 (Cx43) null mice (Cx43e(-/-)). In the cheek pouch, topical tumor necrosis factor-alpha (TNF-alpha; 150 ng/ml, 15 min) caused a sustained increment in the number of leukocytes adhered to venular endothelium (LAV) and located at perivenular regions (LPV). Superfusion with the GJ blockers 18-alpha-glycyrrhetinic acid (AGA; 75 microM) or 18-beta-glycyrrhetinic acid (50 microM) abolished the TNF-alpha-induced increase in LAV and LPV; carbenoxolone (75 microM) or oleamide (100 microM) reduced LAV by 50 and 75%, respectively, and LPV to a lesser extent. None of these GJ blockers modified venular diameter, blood flow, or leukocyte rolling. In contrast, glycyrrhizin (75 microM), a non-GJ blocker analog of AGA, was devoid of effect. Interestingly, when AGA was removed 90 min after TNF-alpha stimulation, LAV started to rise at a similar rate as in control. Conversely, application of AGA 90 min after TNF-alpha reduced the number of previously adhered cells. In WT mice, intrascrotal injection of TNF-alpha (0.5 microg/0.3 ml) increased LAV (fourfold) and LPV (threefold) compared with saline-injected controls. In contrast to the observations in WT animals, TNF-alpha stimulation did not increase LAV or LPV in Cx43e(-/-) mice. These results demonstrate an important role for GJ communication in leukocyte adhesion and transmigration during acute inflammation in vivo and further suggest that endothelial Cx43 is key in these processes. PMID:18599597

  19. GnRH Episodic Secretion Is Altered by Pharmacological Blockade of Gap Junctions: Possible Involvement of Glial Cells.

    PubMed

    Pinet-Charvet, Caroline; Geller, Sarah; Desroziers, Elodie; Ottogalli, Monique; Lomet, Didier; Georgelin, Christine; Tillet, Yves; Franceschini, Isabelle; Vaudin, Pascal; Duittoz, Anne

    2016-01-01

    Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 μM 18-α-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-α-glycyrrhetinic acid washout. PMID:26562259

  20. Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization.

    PubMed

    Bou-Flores, C; Berger, A J

    2001-04-01

    Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal

  1. Dexamethasone metabolism in vitro: species differences.

    PubMed

    Tomlinson, E S; Maggs, J L; Park, B K; Back, D J

    1997-07-01

    Dexamethasone (DEX) is extensively metabolized to 6-hydroxyDEX (6OH-DEX) and side-chain cleaved metabolites in human liver both in vitro and in vivo with CYP3A4 responsible for the formation of 6-hydroxylated products. In the present study, the metabolism of [3H]DEX has been examined in the liver fractions from various mammalian species and metabolite profiles compared with those obtained with human liver microsomes. Metabolites were quantified by radiometric high-pressure liquid chromatography (HPLC) and characterized by liquid chromatography-mass spectrometry (LC-MS) and co-chromatography with chemical standards, where available. 6OH-DEX formation was quantified for each species and the inhibitory potency of ketoconazole at 1 and 20 microM determined. Glycyrrhetinic acid, a specific inhibitor of 11-dehydrogenase, was also used to determine the extent of reductive DEX metabolism. Species differences in metabolite profiles obtained from microsomal incubations were both quantitative and qualitative. 6-Hydroxylation was variable (highest in the hamster) and was not always the major route of metabolism, and formation was sex-specific in the rat (male > female). The inhibition of 6-hydroxylation (CYP3A) by ketoconazole was variable, and indicates that ketoconazole cannot be regarded as a selective inhibitor of CYP3A proteins in all species. Cytosolic incubations produced similar profiles in different species with the formation of a metabolite (M5) which was inhibited by glycyrrhetinic acid and tentatively identified in this study as 11-dehydro-side-chain cleaved DEX (11DH-9alphaF-A). In conclusion, the male rat gave a metabolite profile which was closest to that seen in the human. However, 6-hydroxylation was most extensive in the hamster which may therefore be a suitable model to use for further studies on DEX metabolism by CYP3A. PMID:9408089

  2. Rumen ciliate protozoa contain high concentrations of conjugated linoleic acids and vaccenic acid, yet do not hydrogenate linoleic acid or desaturate stearic acid.

    PubMed

    Devillard, Estelle; McIntosh, Freda M; Newbold, C James; Wallace, R John

    2006-10-01

    Conjugated linoleic acids (CLA) have been shown to improve human health. They are derived from the microbial conversion of dietary linoleic acid (cis-9,cis-12-18 : 2 (LA)) in the rumen. An investigation was undertaken to determine the role of ruminal ciliate protozoa v. bacteria in the formation of CLA and its precursor in animal tissues, vaccenic acid (trans-11-18 : 1 (VA)). Mixed protozoa from the sheep rumen contained at least two to three times more unsaturated fatty acids, including CLA and VA, than bacteria. Different species had different composition, with larger fibrolytic species such as Epidinium ecaudatum caudatum containing more than ten times more CLA and VA than some small species, including Entodinium nanellum. In incubations with ruminal microbial fractions (bacterial fraction (BAC), protozoal fraction (PRO)), LA metabolism was very similar in strained ruminal fluid (SRF) and in the BAC, while the PRO had LA-metabolising activity an order of magnitude lower. Using PCR-based methods, no genes homologous to fatty acid desaturase genes were found in cDNA libraries from ruminal protozoa. The absence of an alternative route of VA/CLA formation via desaturation of stearate was confirmed by incubations of SRF, BAC or PRO with [14C]stearate. Thus, although protozoa are rich in CLA and VA, they appear to lack the ability to form these two fatty acids from LA or stearate. The most likely explanation is that protozoa preferentially incorporate CLA and VA formed by bacteria. The implication of the present findings is that the flow of unsaturated fatty acids, including CLA and VA, from the rumen could depend on the flow of protozoa rather than bacteria. PMID:17010229

  3. Floating-pulsatile release multiparticulate system for chronopharmacotherapy: effect of some hydrophobic additives on the buoyancy and release behavior of particles.

    PubMed

    Maghsoodi, M

    2014-01-01

    A blend of floating and pulsatile principles of a drug delivery system would have the advantage that a drug can be released in the upper gastrointestinal (GI) tract after a lag period, which is anticipated for chronotherapy. In this study, microballoons were prepared by an emulsion solvent diffusion technique using Eudragit S100, and hydrophobic additive (magnesium stearate, stearic acid or talc) for time- and site-specific drug release of piroxicam. The effect of hydrophobic additives on the production yield of floating microparticles, buoyant ability for 8 h, release of drug in simulated GI fluids (simulated gastric fluid [SGF] and simulated intestinal fluid [SIF]), mean particle size, apparent particle density, encapsulation efficiency of drug and physical state of incorporated drug were studied. Both production yield and buoyancy of the microballoons were affected by additives in the following order: magnesium stearate, stearic acid>free-additive>talc. The observed difference in yield and the buoyancy of the microballoons could be attributed to the hydrophobic character of the additives and the shell rigidity of the obtained microballoons. Incorporation of hydrophobic additives in the microballoons was found to impart the desired release properties to the microballoons by providing a 2-phase release pattern with initial slow release (5-6%) through 8 h in SGF followed by rapid pulse release (>92%) in SIF through 15 min. The microballoons co-formulated with magnesium stearate or stearic acid, combining excellent buoyancy and suitable drug release pattern of piroxicam, could be useful in chronopharmacotherapy in arthritis. PMID:23950100

  4. Effects of the metal type and the roughness of the die wall on the expended work for tablet ejection.

    PubMed

    Otz, M; Thoma, H

    2000-01-01

    The aim of the present work was to obtain an impression about the consequences for the tableting process when dies of different quality are used. Two hard metal dies and one die made from tool steel, each with a distinct roughness of the die wall, were compared by compacting dry-blended powder mixtures on an eccentric tablet press. The feasibility of the tableting process was assessed by quantifying the ejection force and the work expended by the lower punch during a first phase of the ejection process. With decreasing amounts of lubricant, abrupt permanent impacts were observed leading to conditions at which an ejection was no longer possible. This observation did not depend on the roughness of the die wall used or on the compaction pressure, but strongly depended on the metal type of the die used and on the tested formulation. For the tool steel no difference was found in this respect between the two tested formulations (0.5% versus 2% silica aerogel). In either case, a concentration of 0.3% magnesium stearate was sufficient; however, a concentration of 0.2% magnesium stearate was not sufficient. For both hard metal dies, concentrations of 0.3% (0.5% silica aerogel) and 0.5% magnesium stearate (2% silica aerogel) were definitely not sufficient. Within the ranges above a minimum lubrication, the ejection force and the ejection work increased with the degree of the die wall roughness on a scale comparable to that of the tested formulation factors. In particular, if changes of the die tooling are likely to occur in the life cycle of a product, it is highly recommended that the quality of the dies be considered in the development phase. PMID:10669914

  5. Chemical Constituents of Trichilia hirta (Meliaceae).

    PubMed

    Vieira, Milena G Curcino; dos Santos, Frances R; Braz Filho, Raimundo; Vieira, Ivo J Curcino

    2016-05-01

    A novel oleanane-type triterpene, 15-chloro-β-amyrone (1), was isolated from Trichilia hirta, together with the known compounds taraxer-3-one (2) and β-taraxerol (3), along with two novel esters, 3-(isobutyryloxy)-2,2,4-trimethylpenty palmitate (4) and 3-(isobutyryloxy)-2,2,3-trimethylpenty stearate (5), and the known 3-hydroxy-2,2,4-trimethylpentyl isobutyrate (6). These compounds were characterized on the basis of their spectroscopic and HRSEIMS data and by comparison with literature data. PMID:27319125

  6. A 212Pb generator based on a 228Th source.

    PubMed

    Hassfjell, S

    2001-10-01

    A two-compartment 212Pb generator has been constructed and characterized physically and chemically. It is based on transport by airflow of gaseous 220Rn emanating from thin layers of [228Th]barium stearate. 220Rn is collected in a glass bubbler by extraction into an organic solvent and solidified at temperatures below -72 degrees C. Tracer studies show that the decay product 212Pb can be recovered with approximately 70% yield. It is suggested that this generator design could accommodate therapeutic levels of 212Pb/228Th. PMID:11545493

  7. Effect of vapor phase corrosion inhibitor on microbial corrosion of aluminum alloys.

    PubMed

    Yang, S S; Ku, C H; Bor, H J; Lin, Y T

    1996-02-01

    Vapor phase corrosion inhibitors were used to investigate the antimicrobial activities and anticorrosion of aluminum alloy. Aspergillus flavus, A. niger, A. versicolor, Chaetomium globosum and Penicillium funiculosum had moderate to abundant growth on the aluminum alloy AA 1100 at Aw 0.901, while there was less growth at Aw 0.842. High humidity stimulated microbial growth and induced microbial corrosion. Dicyclohexylammonium carbonate had a high inhibitory effect on the growth of test fungi and the microbial corrosion of aluminum alloy, dicyclohexylammonium caprate and dicyclohexylammonium stearate were the next. Aluminum alloy coating with vapor phase corrosion inhibitor could prevent microbial growth and retard microbial corrosion. PMID:10592784

  8. Characterization and cloning of a stearoyl/oleoyl specific fatty acyl-acyl carrier protein thioesterase from the seeds of Madhuca longifolia (latifolia).

    PubMed

    Ghosh, Santosh K; Bhattacharjee, Ashish; Jha, Jyoti K; Mondal, Ashis K; Maiti, Mrinal K; Basu, Asitava; Ghosh, Dolly; Ghosh, Sudhamoy; Sen, Soumitra K

    2007-12-01

    Deposition of oleate, stearate and palmitate at the later stages of seed development in Mahua (Madhuca longifolia (latifolia)), a tropical non-conventional oil seed plant, has been found to be the characteristic feature of the regulatory mechanism that produces the saturated fatty acid rich Mahua seed fat (commonly known as Mowrah fat). Although, the content of palmitate has been observed to be higher than that of stearate at the initial stages of seed development, it goes down when the stearate and oleate contents consistently rise till maturity. The present study was undertaken in order to identify the kind of acyl-ACP thioesterase(s) that drives the characteristic composition of signature fatty acids (oleate 37%, palmitate 25%, stearate 23%, linoleate 12.5%) in its seed oil at maturity. The relative Fat activities in the crude protein extracts of the matured seeds towards three thioester substrates (oleoyl-, stearoyl- and palmitoyl-ACP) have been found to be present in the following respective ratio 100:31:8. Upon further purification of the crude extract, the search revealed the presence of two partially purified thioesterases: a long-chain oleoyl preferring house-keeping LC-Fat and a novel stearoyl-oleoyl preferring SO-Fat. The characteristic accumulation of oleate and linoleate in the M. latifolia seed fat is believed to be primarily due to the thioesterase activity of the LC-Fat or MlFatA. On the other hand, the SO-Fat showed almost equal substrate specificity towards stearoyl- and oleoyl-ACP, when its activity towards palmitoyl-ACP compared to stearoyl-ACP was only about 12%. An RT-PCR based technique for cloning of a DNA fragment from the mRNA pool of the developing seed followed by nucleotide sequencing resulted in the identification of a FatB type of thioesterase gene (MlFatB). This gene was found to exist as a single copy in the mother plant genome. Ectopic expression of this MlFatB gene product in E. coli strain fadD88 further proved that it induced a

  9. Technique for injection into the sciatic nerve of the mouse for quantitative in vivo metabolic studies

    SciTech Connect

    Heape, A.M.; Boiron, F.; Cassagne, C.

    1986-05-15

    In this paper we describe a technique for intraneural injections, applicable to mouse peripheral nerves, which, compared with previous techniques, reduces trauma to the nerves and increases the level and reduces the variability of label recovery. Our technique employs glass needles (tip diameter, 50 micron) linked to a peristaltic pump by polyethylene tubing to inject small volumes (in the microliter range) of radiolabeled substrate solutions into mouse sciatic nerves, and allows the recovery of 20.9 +/- 1.9% (mean +/- standard deviation) and 30.5 +/- 4.8% of the injected radioactivity for 2 microliter (3H)acetate and 0.5 microliter of (3H)stearate, respectively.

  10. Preparation of PbS and PbSe nanocrystals by a new solvothermal route

    SciTech Connect

    Gautam, Ujjal K.; Seshadri, Ram

    2004-04-02

    A new solvothermal route for the preparation of nanocrystals of PbS and PbSe, involving the reaction of lead stearate with sulfur or selenium and tetralin (tetrahydronaphthalene) in toluene solvent is described. Tetralin in the presence of S/Se gives H{sub 2}S/H{sub 2}Se and gets aromatized to naphthalene. The nanocrystals have been characterized by powder X-ray diffraction and electron microscopy. Use of surfactant Triton X-100 (polyoxyethylene(10)isooctylphenyl ether) resulted in both nanorods and nanoparticles of PbSe. Capping by citric acid and malonic acid reduce the particle sizes to less than 10 nm.

  11. Raman Microimaging of Polymer Blends

    NASA Astrophysics Data System (ADS)

    Song, Guanghua; Waldek Zerda, Tadeusz

    2001-10-01

    Raman microimaging was used to estimate the effect of the silica filler on phase separation in polymer blends composed of brominated poly(isobutylene-co-para-methylstyrene)(BIMS),natural rubber, synthetic rubber, and cis-1-4-polybutadiene(BR).the domain sizes,relative concentration of polymer components within domains ,and distribution of particulate silica filler and zinc stearate curative were characterized for blends of different compositions and history of aging treatments. The presence of increased concentrations of precipitated silica results in better polymer morphology since domain sizes are reduced.

  12. Efficiency of metal activators of accelerated sulfur vulcanization

    SciTech Connect

    Duchacek, V.; Kuta, A.; Pribyl, P. )

    1993-01-20

    The effects of copper, mercury, nickel, zinc, cadmium, indium, magnesium, and calcium stearates on the course of N-cyclohexyl-2-benzthiazylsulphenamide-accelerated sulfur vulcanization of natural rubber have been investigated on the basis of curemeter measurements at 145 C. The differences in the efficiencies of these metal activators of accelerated sulfur vulcanization have been discussed from the points of view of the electron configurations of the metals and their affinities to sulfur. The authors attempted to determine why zinc oxide is generally accepted as the best metal vulcanization activator.

  13. Fatty Acid-Elongating Activity in Rapidly Expanding Leek Epidermis.

    PubMed Central

    Evenson, K. J.; Post-Beittenmiller, D.

    1995-01-01

    A microsomal fatty acid elongase activity measured in epidermis of rapidly expanding leek (Allium porrum L.) was 10-fold higher in specific activity than preparations from store-bought leek. These preparations elongated acyl chains effectively using endogenous or supplied primers. Elongation of C20:0 was specifically inhibited by 2 [mu]M cerulenin, and labeling experiments with [3H]cerulenin labeled two polypeptides (65 and 88 kD). ATP was required for maximal elongase activity in expanding leaves but was lost in nonexpanding tissues. Both [14C]stearoyl-coenzyme A (CoA) and [14C]stearate were maximally elongated in the presence of ATP. Addition of fully reduced CoA, however, inhibited [14C]stearate elongation, suggesting that stearoyl-CoA synthesis was not a prerequisite for elongation. Furthermore, microsomes preincubated with [14C]stearoyl-CoA plus ATP resulted in loss of radiolabel from the acyl-CoA pool without a corresponding loss in elongating activity. The lack of correlation between elongating activity and the label retained in the putative acyl-CoA substrate pool suggests that acyl-CoAs may not be the immediate precursors for elongation and that ATP plays a critical, yet undefined, role in the elongation process. We propose that an ATP-dependent elongating activity may generate the long-chain fatty acids required for wax biosynthesis. PMID:12228624

  14. In vivo acylation of rat brain myelin proteolipid protein.

    PubMed

    Agrawal, H C; Randle, C L; Agrawal, D

    1982-04-25

    Examination of brain myelin proteins by sodium dodecyl sulfate-gel electrophoresis followed by fluorography clearly showed that both proteolipid protein (PLP) and DM-20 were acylated 24 h after the intracerebral injection of 30-day-old rats with [3H]palmitic acid. The radioactivity associated with PLP remained after purification, re-electrophoresis, and fluorography. Most of the radioactivity associated with PLP was removed when the gels were treated with hydroxylamine and then fluorographed, indicating that fatty acids were bound to PLP by ester linkage. Cleavage of purified PLP with methanolic sodium hydroxide readily released almost all protein-bound radioactivity. Thin layer chromatography of this material on both silver nitrate and reverse-phase plates provided evidence that most of the radioactivity co-migrated with methyl palmitate (77%) and methyl stearate (19%); however, some radioactivity was associated with methyl oleate (4%). Gas-liquid chromatography of the fatty acids associated with PLP distinctly revealed the presence of methyl palmitate and a detectable peak of methyl stearate. PMID:7068653

  15. Enzyme-Catalyzed Regioselective Modification of Starch Nanoparticles

    SciTech Connect

    Chakraborty, Soma; Sahoo, Bishwabhusan; Teraoka, Iwao; Miller, Lisa M.; Gross, Richard A.

    2004-12-13

    The selective esterification of starch nanoparticles was performed using as catalyst Candida antartica Lipase B (CAL-B) in its immobilized (Novozym 435) and free (SP-525) forms. The starch nanoparticles were made accessible for acylation reactions by formation of Aerosol-OT (AOT, bis(2-ethylhexyl)sodium sulfosuccinate) stabilized microemulsions. Starch nanoparticles in microemulsions were reacted with vinyl stearate, ε-caprolactone, and maleic anhydride at 40 °C for 48 h to give starch esters with degrees of substitution (DS) of 0.8, 0.6, and 0.4, respectively. Substitution occurred regioselectively at the C-6 position of the glucose repeat units. Infrared microspectroscopy (IRMS) revealed that AOT-coated starch nanoparticles diffuse into the outer 50 μm shell of catalyst beads. Thus, even though CAL-B is immobilized within a macroporous resin, CAL-B is sufficiently accessible to the starch nanoparticles. When free CAL-B was incorporated along with starch within AOT-coated reversed micelles, CAL-B was also active and catalyzed the acylation with vinyl stearate (24 h, 40 °C) to give DS = 0.5. After removal of surfactant from the modified starch nanoparticles, they were dispersed in DMSO or water and were shown to retain their nanodimensions.

  16. Great advantages in using a natural rubber instead of a synthetic SBR in a pro-oxidant system for degradable LDPE.

    PubMed

    Khabbaz, F; Albertsson, A C

    2000-01-01

    Different pro-oxidant systems are used in degradable low-density polyethylene (LDPE). The main question is the degradation products and not the degradation time from the used materials. The pro-oxidant formulation used consisted of manganese stearate and natural rubber (NR) or manganese stearate and a synthetic, styrene-butadiene copolymer rubber (SBR). The samples were heated in air at 100 degrees C in sealed glass vials. The molecular weight changes were measured by size exclusion chromatography (SEC). The volatile and nonvolatile degradation products have been identified by gas chromatography-mass spectrometry (GC/MS). A wide variety of degradation products were identified, including ketones, carboxylic acids, keto acids, dicarboxylic acids, and furanones as a homologous series. Benzaldehyde, acetophenone, benzoic acid, benzyl benzoate, and two benzene derivative compounds were identified only in the LDPE-SBR system. These aromatic compounds originate from the styrene part of SBR. The advantages using pro-oxidant containing NR are more effective degradation of LDPE without any aromatic degradation products. PMID:11710197

  17. Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings.

    PubMed

    Uranga, Carla C; Beld, Joris; Mrse, Anthony; Córdova-Guerrero, Iván; Burkart, Michael D; Hernández-Martínez, Rufina

    2016-04-01

    The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. PMID:26926564

  18. Structural investigation of the covalent and electrostatic binding of yeast cytochrome c to the surface of various ultrathin lipid multilayers using x-ray diffraction.

    PubMed Central

    Pachence, J M; Blasie, J K

    1991-01-01

    X-Ray diffraction was used to characterize the profile structures of ultrathin lipid multilayers having a bound surface layer of cytochrome c. The lipid multilayers were formed on an alkylated glass surface, using the Langmuir-Blodgett method. The ultrathin lipid multilayers of this study were: five monolayers of arachidic acid, four monolayers of arachidic acid with a surface monolayer of dimyristoyl phosphatidylserine, and four monolayers of arachidic acid acid with a surface monolayer of thioethyl stearate. Both the phosphatidylserine and the thioethyl stearate surfaces were found previously to covalently bind yeast cytochrome c, while the arachidic acid surface electrostatically binds yeast cytochrome c. Meridional x-ray diffraction data were collected from these lipid multilayer films with and without a bound yeast cytochrome c surface layer. A box refinement technique, previously shown to be effective in deriving the profile structures of ultrathin multilayer lipid films with and without electrostatically bound cytochrome c, was used to determine the multilayer electron density profiles. The surface monolayer of bound cytochrome c was readily apparent upon comparison of the multilayer electron density profiles for the various pairs of ultrathin multilayer films plus/minus cytochrome c for all cases. In addition, cytochrome c binding to the multilayer surface significantly perturbs the underlying lipid monolayers. PMID:1648415

  19. Isoelectric points and surface hydrophobicity of Gram-positive cocci as determined by cross-partition and hydrophobic affinity partition in aqueous two-phase systems.

    PubMed Central

    Miörner, H; Albertsson, P A; Kronvall, G

    1982-01-01

    Thirty-nine streptococcal strains belonging to groups A, C, and G and 12 staphylococcal strains were investigated with respect to surface charge and hydrophobicity. Isoelectric points of the bacteria were determined by cross-partition experiments in dextran-polyethylene glycol two-phase systems containing charged polymers. The results obtained indicate that group A, C, and G streptococci have isoelectric points of pH 3.75 +/- 0.15 standard deviation. Staphylococci show an isoelectric point of around pH 2 and thereby differ markedly from the streptococci. Pretreatment of bacteria with human serum resulted in a significant change in the isoelectric points of streptococci. In a second series of experiments, an aqueous dextran-polyethylene glycol two-phase system containing polyethylene glycol palmitate or stearate was used to study the hydrophobic surface properties of the bacterial cells. The partition of the staphylococci was not influenced by the addition of up to 1% (wt/wt) polyethylene glycol palmitate or stearate, whereas the streptococci showed a large variation in affinity for polyethylene glycol-bound hydrophobic groups. The bacterial strains included in the study were also tested for uptake of human serum proteins. A positive correlation was found between the hydrophobic affinity of group A streptococci and the density of receptors for aggregated beta-2-microglobulin. PMID:7042571

  20. The adjuvant activity of fatty acid esters. The role of acyl chain length and degree of saturation.

    PubMed Central

    Bomford, R

    1981-01-01

    Water-in-oil emulsions of metabolizable fatty acid esters, with the non-toxic surfactant Pluronic L122 as emulsifying agent, potentiated the humoral response to bovine serum albumin and staphylococcal toxoid in the mouse. Adjuvant activity was increased by changing the chemical nature of the esters as follows: (i) using a series of ethyl esters, adjuvant activity appeared when the acyl chain length of the fatty acid component was 16 or greater; (ii) isobutyl and isopropyl esters of palmitic acid (C16:0) were superior to ethyl; (iii) the ethyl esters of oleic (C18:1) and linoleic (C18:2) acids were better than stearic (C18:0). Since emulsions prepared with longer chain saturated esters are very viscous or solid at room temperature, and unsaturated esters are chemically reactive, emulsions were prepared with differing proportions of ethyl caprate (C10:0) and butyl stearate. At a ratio of 9:1 the emulsions possessed the low viscosity of ethyl caprate, but gained the adjuvant activity of butyl stearate. 125I-labelled BSA was retained in the footpad to a significantly greater extent than with a caprate emulsion, but reasons are given for believing that slow release of antigen is not the only mechanism of adjuvant activity. The ester emulsions caused more acute but less chronic local inflammation (footpad swelling) than Freund's incomplete adjuvant. PMID:7275184

  1. Synthesis and catalytic properties of highly ordered mesostructured silica-pillared α-zirconium phosphate: Self-assembly via interlayered templating method

    NASA Astrophysics Data System (ADS)

    Mao, Huihui; Lu, Xinhao; Li, Mingshi; Yang, Jihe; Li, Baoshan

    2013-07-01

    We present a facile organic surfactant templating self-assembly method with suitable cationic surfactant method for silica-pillared α-ZrP with ordered interlayered mesoporous structure. The synthetic silica-pillared α-ZrP powders with interlayer spaces and interlayer pore sizes ranging from 3.0 to 3.7 nm and 1.4 to 2.1 nm by varying the molar ratio of surfactant/α-ZrP during self-assembly process. The structure and properties of the silica-pillared α-ZrP powders were characterized by using XRD, SEM/TEM, FT-IR, TPD and N2 adsorption-desorption isotherms systematically. A bilayers arrangement-molecular micelles1 phase transformation formation mechanism was proposed for the molecular assembly. The acylation reaction of fatty acid methyl esters (methyl stearate) with ethanolamine to form monoethanolamides was chosen as a probe reaction to evaluate the catalytic activity of the resulting microspherical silica-pillared α-ZrP materials, which showed high activity, with about 92.9% methyl stearate conversion at 393 K for 16 h. The enhanced performance in the reaction is determined by the large surface area, ordered pore size and the increased number of acidic sites in the silica-pillared α-ZrP powders.

  2. Photodegradation of phosmet in wool wax models and on sheep wool: determination of wool wax bound phosmet by means of isotope ratio mass spectrometry.

    PubMed

    Sinderhauf, Katrin; Schwack, Wolfgang

    2005-06-15

    The photochemical reactions of phosmet, an organophosphorus insecticide used for plant protection and for control of ectoparasites on productive livestock, were studied in the presence of wool wax. Induced by UV light, phosmet features numerous degradation pathways as well as photoaddition reactions with lipid structure moieties. In model irradiation experiments of phosmet in mixtures of solvents (cyclohexane, cyclohexene, 2-propanol) and fatty acid methyl esters (methyl stearate, methyl oleate, 12-hydroxymethyl stearate), both adjusted to the hydroxyl and iodine values of wool wax, half-lives were determined to be approximately 7 and 16 h, respectively. Irradiation of phosmet on crude sheep wool resulted in a degradation rate of 65% after 24 h. In tracer studies with stable isotope labeled phosmet ([15N]phosmet) in commercial lanolin and on raw sheep wool, employing a sunlight simulator and natural sunlight, wool wax bound phosmet was formed. After extraction and measurement by elemental analyzer/isotope ratio mass spectrometry, delta15N values of the phosmet-free wool wax fractions were notably increased as compared to the value of natural lanolin. Calculated from the delta15N values, an average of 13.9/15.6% (sunlight simulator/natural sunlight) was bound to wool wax lipids after irradiation of thin films of commercial lanolin. In experiments with sheep wool, 13.2 and 15.4%, respectively, were detected as wax-bound. PMID:15941329

  3. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms.

    PubMed

    Tiţa, Bogdan; Fuliaş, Adriana; Bandur, Geza; Marian, Eleonora; Tiţa, Dumitru

    2011-09-10

    Thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) techniques were used for assessing the compatibility between ketoprofen (KT) and several excipients as: corn starch, microcrystalline cellulose (PH 101 and PH 102), colloidal silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone K30, magnesium stearate and talc, commonly used in the pharmaceutical form. In order to investigate the possible interactions between the components, the thermal curves of KT and each selected excipients were compared with those of their 1:1 (w/w) physical mixtures. For KT, the DSC curves have shown a sharp endothermic peak at 96.8 °C which corresponds to the melting process (literature value: 94-97 °C), respectively the TG curves demonstrated a simple stage of mass loss in the temperature range of 235-400 °C. FT-IR spectroscopy and X-ray powder diffraction (XRPD) were used as complementary techniques to adequately implement and assist in interpretation of the DSC results. On the basis of thermal results, a possible interaction was found between the KT with polyvinylpyrrolidone K30 and magnesium stearate, which could influence the stability of the KT in the binary mixtures. These possible incompatibilities were confirmed by FT-IR and X-ray analysis. PMID:21665404

  4. Effect of silicification on the tableting performance of cellulose ii: a novel multifunctional excipient.

    PubMed

    Rojas, John; Kumar, Vijay

    2012-01-01

    The effect of silicification on the tableting performance of microcrystalline cellulose II (MCCII) was assessed through coprocessing with fumed silica via spray drying and wet granulation at the 98:2, 95:5, 90:10 and 80:20 ratios. Compacts produced by spray drying and wet granulation rendered better tensile strength than MCCII. The Kawakita and Heckel models implied that silicification increased compressibility and decreased the plastic deforming behavior and densification by die filling at the early stage of compression for MCCII. It also decreased the sensitivity to hydrophobic lubricants such as magnesium stearate, especially for the spray-dried products due to the competing effect with magnesium stearate. Further, silicification decreased the high elastic recovery typical of MCCII due to the increase in specific surface area and fragmenting behavior which contributed to the formation of stronger compacts. Moreover, silicification did not affect the fast disintegrating properties and release rates of poorly soluble drugs such as griseofulvin formulated in tablets compared to those of Prosolv® SMCC 50 and Prosolv® SMCC 90. The new silicified materials are appropriate to formulate fast disintegrating tablets by direct compression. PMID:22689398

  5. The role of several l-HPCs in preventing tablet capping during direct compression of metronidazole.

    PubMed

    Martino, Piera Di; Malaj, Ledjan; Censi, Roberta; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

    2007-12-01

    Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant. Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression. PMID:18097804

  6. Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.

    PubMed

    Crissey, S; Ange, K; Slifka, K; Bowen, P; Stacewicz-Sapuntzakis, M; Langman, C; Sadler, W; Ward, A

    2001-01-01

    Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them. PMID:11137448

  7. Influence of different emulsifiers on characteristics of eggless cake containing soy milk: Modeling of physical and sensory properties by mixture experimental design.

    PubMed

    Rahmati, Nazanin Fatemeh; Mazaheri Tehrani, Mostafa

    2014-09-01

    Emulsifiers of different structures and functionalities are important ingredients usually used in baking cakes with satisfactory properties. In this study, three emulsifiers including distilled glycerol mono stearate (DGMS), lecithin and sorbitan mono stearate (SMS) were used to bake seven eggless cakes containing soy milk and optimization was performed by using mixture experimental design to produce an eggless cake sample with optimized properties. Physical properties of cake batters (viscosity, specific gravity and stability), cake quality parameters (moisture loss, density, specific volume, volume index, contour, symmetry, color and texture) and sensory attributes of eggless cakes were analyzed to investigate functional potential of the emulsifiers and results were compared with those of control cake containing egg. Almost in all cases emulsifiers, compared to the control cake, changed properties of eggless cakes significantly. Regarding models of different response variables (except for some properties) and their high R(2) (99.51-100), it could be concluded that models obtained by mixture design were significantly fitted for the studied responses. PMID:25190826

  8. Formulation, characterization and evaluation of the effect of polymer concentration on the release behavior of insulin-loaded Eudragit®-entrapped mucoadhesive microspheres

    PubMed Central

    Kenechukwu, Franklin C.; Momoh, Mumuni A.

    2016-01-01

    Introduction: The aim of this study was to use Eudragit® RL 100 (pH-independent polymer) and magnesium stearate (a hydrophobic droplet stabilizer) in combination to improve the controlled release effect of insulin-loaded Eudragit® entrapped microspheres prepared by the emulsification-coacervation technique. Materials and Methods: Mucoadhesive insulin-loaded microspheres containing magnesium stearate and varying proportions of Eudragit® RL 100 were prepared by the emulsification-coacervation technique and evaluated for thermal properties, physicochemical performance, and in vitro dissolution in acidic and subsequently basic media. Results: Stable, spherical, brownish, discrete, free-flowing and mucoadhesive insulin-loaded microspheres with size range of 14.20 ± 0.30-19.80 ± 0.60 μm and loading efficiency of 74.55 ± 1.05-75.90 ± 1.94% were formed. After 3 h, microspheres prepared with insulin: Eudragit® RL 100 ratios of 1:4, 1:6, and 1:8 released 73.40 ± 1.38, 66.20 ± 1.59, and 71.30 ± 1.27 (%) of insulin, respectively. Conclusion: The physicochemical and physico-technical properties of the microspheres developed in this study demonstrated the effectiveness of the Eudragit® RL entrapped mucoadhesive microspheres (prepared by the emulsification-coacervation technique using varying polymer concentration) as a carrier system for oral insulin delivery. PMID:27051626

  9. Influence of coating material on the flowability and dissolution of dry-coated fine ibuprofen powders.

    PubMed

    Qu, Li; Zhou, Qi Tony; Denman, John A; Stewart, Peter J; Hapgood, Karen P; Morton, David A V

    2015-10-12

    This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating. PMID:26215464

  10. Determination of fatty acid ethyl esters in hair by GC-MS and application in a population of cocaine users.

    PubMed

    Politi, Lucia; Mari, Francesco; Furlanetto, Sandra; Del Bravo, Ester; Bertol, Elisabetta

    2011-04-01

    A gas chromatography-mass spectrometry method for the determination of ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate in hair samples was developed, validated and applied to real samples. Ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate are fatty acid ethyl esters (FAEE) which are known to be direct biotransformation products of ethanol. Their presence in the body fluids and tissue is therefore indicative of alcohol intake and, in particular, FAEE concentration in hair higher than 0.5 ng/mg is indicative of excessive chronic alcohol consumption. The method was applied to 80 hair samples formerly found positive for cocaine and FAEE analytical results were compared with the presence of cocaethylene, a cocaine metabolite formed only when alcohol and cocaine are used together. According to our data the two biomarkers (FAEE and cocaethylene in hair) are tools of great value in the assessment of the diagnosis of use of cocaine and ethanol. In fact, discrepancies were noted and might be related to various factors including differences in consumption habits and thus permitting to distinguish the use of both substances non-concurrently or concurrently. Also, the determination of both markers may, in some cases, discriminate the use of moderate or heavy alcohol amounts when associated with cocaine. Finally, in a population of non-cocaine-users our results support FAEE as valuable means in the assessment of excessive alcohol chronic use. PMID:21159458

  11. Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion.

    PubMed

    Démuth, Balázs; Farkas, Attila; Balogh, Attila; Bartosiewicz, Karolina; Kállai-Szabó, Barnabás; Bertels, Johny; Vigh, Tamás; Mensch, Jurgen; Verreck, Geert; Van Assche, Ivo; Marosi, György; Nagy, Zsombor K

    2016-09-01

    Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation is in a quite early phase. Development of high speed electrospinning opened up the possibility to study tableting of electrospun solid dispersions (containing polyvinylpyrrolidone-vinyl acetate and itraconazole [ITR] in this case). This work was conducted to investigate the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting. The dissolution rates from tablets proved to be mainly composition dependent. Magnesium stearate acted as a nucleation promoting agent (providing an active hydrophobic environment for crystallization of ITR) hindering the total dissolution of ITR. This crystallization process proved to be temperature dependent as well. However, the extent of dissolution of more than 95% was realizable when a less hydrophobic lubricant, sodium stearyl fumarate (soluble in the medium), was applied. Magnesium stearate induced crystallization even if it was put in the dissolution medium next to proper tablets. After optimization of the composition, scaled-up tableting on a rotary press was carried out. Appropriate dissolution of ITR from tablets was maintained for 3 months at 25°C/60% relative humidity. HPLC measurements confirmed that ITR was chemically stable both in the course of downstream processing and storage. PMID:27290626

  12. Water-repellent coatings prepared by modification of ZnO nanoparticles.

    PubMed

    Chakradhar, R P S; Dinesh Kumar, V

    2012-08-01

    Superhydrophobic coatings with a static water contact angle (WCA)>150° were prepared by modifying ZnO nanoparticles with stearic acid (ZnO@SA). ZnO nanoparticles of size ∼14nm were prepared by solution combustion method. X-ray diffraction (XRD) studies reveal that as prepared ZnO has hexagonal wurtzite structure whereas the modified coatings convert to zinc stearate. Field emission scanning electron micrographs (FE-SEM) show the dual morphology of the coatings exhibiting both particles and flakes. The flakes are highly fluffy in nature with voids and nanopores. Fourier transformed infrared (FTIR) spectrum shows the stearate ion co-ordinates with Zn(2+) in the bidentate form. The surface properties such as surface free energy (γ(p)) and work of adhesion (W) of the unmodified and modified ZnO coatings have been evaluated. The electron paramagnetic resonance (EPR) spectroscopy reveals that surface defects play a major role in the wetting behavior. PMID:22575349

  13. Development of liposomal salbutamol sulfate dry powder inhaler formulation.

    PubMed

    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang

    2010-01-01

    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state. PMID:20190418

  14. Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.

    PubMed

    Ahrabi, S F; Heinämäki, J; Sande, S A; Graffner, C

    2000-05-01

    The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl. PMID:10767600

  15. Synthesis and electrochemical property of xLi2MnO3·(1 - x)LiMnO2 composite cathode materials derived from partially reduced Li2MnO3

    NASA Astrophysics Data System (ADS)

    Zhang, Qinggang; Peng, Tianyou; Zhan, Dan; Hu, Xiaohong

    2014-03-01

    xLi2MnO3·(1 - x)LiMnO2 (x = 0.39, 0.48, 0.57, 0.74) composites with a layered structure of C2/m symmetry are firstly synthesized with the assistance of the pyrolysis of in situ formed lithium stearate, which can partially reduce the electrochemically inactive Li2MnO3. The obtained composites used as cathode material of Li-ion battery exhibit excellent electrochemical property such as high reversible capacity (>210 mAh g-1) and good rate performance with an initial charge/discharge profile similar to the Li-rich solid solution materials in the range of 2.0-4.8 V. Among those obtained composites, 0.57Li2MnO3·0.43LiMnO2 has the best cyclic and rate performance, because it contains enough Li2MnO3 to stabilize the structure of LiMnO2 and has a suitable average valence state of Mn to balance the reversible capacity and Jahn-Teller effect. The present findings indicate that the pyrolysis of in situ formed lithium stearate on Li2MnO3 particle surfaces is a simple and effective way to obtain Mn-based layered Li-rich composite cathode materials of Li-ion battery with good cyclic and rate performance.

  16. Effect of particle shape on powder flowability of microcrystalline cellulose as determined using the vibration shear tube method.

    PubMed

    Horio, Takehiko; Yasuda, Masatoshi; Matsusaka, Shuji

    2014-10-01

    Powder flowability of microcrystalline cellulose particles having different particle shapes, whose aspect ratios ranged from 1.8 to 6.4, was measured using the vibration shear tube method. Particles lubricated with magnesium stearate were also investigated in order to evaluate the effect of surface modification on powder flowability. Particles were discharged through a narrow gap between a vibrating tube edge and a flat bottom surface, where each particle experienced high shear forces, thus, overcoming adhesion and friction forces. Vibration amplitude was increased at a constant rate during measurement and the masses of the discharged particles were measured at consistent time intervals. Flowability profiles, i.e., the relationships between the mass flow rates of the discharged particles and their vibration accelerations, were obtained from these measurements. Critical vibration accelerations and characteristic mass flow rates were then determined from flowability profiles in order to evaluate static and dynamic friction properties. The results were compared with those obtained using conventional methods. It was found that angle of repose and compressibility were related to static and dynamic friction properties. Furthermore, it was found that particle aspect ratio more significantly affects powder flowability than does lubrication with magnesium stearate. PMID:25079435

  17. Design of covalently functionalized carbon nanotubes filled with metal oxide nanoparticles for imaging, therapy, and magnetic manipulation.

    PubMed

    Liu, Xiaojie; Marangon, Iris; Melinte, Georgian; Wilhelm, Claire; Ménard-Moyon, Cécilia; Pichon, Benoit P; Ersen, Ovidiu; Aubertin, Kelly; Baaziz, Walid; Pham-Huu, Cuong; Bégin-Colin, Sylvie; Bianco, Alberto; Gazeau, Florence; Bégin, Dominique

    2014-11-25

    Nanocomposites combining multiple functionalities in one single nano-object hold great promise for biomedical applications. In this work, carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We propose here a filling process using CNTs as nanoreactors for high-yield in situ growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups via the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water-dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing control of their orientation within the cell and inducing submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs. PMID:25343751

  18. Investigating critical effects of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose tablets.

    PubMed

    Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree

    2016-01-01

    The research envisaged focuses on vital impacts of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose (EC) tablets using prednisone as a model drug. Several lubricants and glidants such as magnesium stearate, colloidal SiO2, sodium stearyl fumarate, talc, stearic acid, polyethylene glycol (6000) and glyceryl behenate were investigated to understand their effects on lag time by changing their concentrations in outer coat. Further, the effects of hydrophilic additives on lag time were examined for hydroxypropylmethylcellulose (E5), hydroxypropylcellulose (EF and SSL), povidone (K30), copovidone, polyethylene glycol (4000), lactose and mannitol. In vitro drug release testing revealed that each selected lubricant/glidant, if present even at concentration of 0.25% w/w, significantly reduced the lag time of press coated tablets. Specifically, colloidal SiO2 and/or magnesium stearate were detrimental while other lubricants/glidants were relatively less injurious. Among hydrophilic additives, freely water soluble fillers had utmost influence in lag time, whereas, comparatively less impact was observed with polymeric binders. Concisely, glidant and lubricant should be chosen to have minimal impact on lag time and further judicious selection of hydrophilic additives should be exercised for modulating lag time of pulsatile release formulations. PMID:25566928

  19. Particle interaction of lubricated or unlubricated binary mixtures according to their particle size and densification mechanism.

    PubMed

    Di Martino, Piera; Joiris, Etienne; Martelli, Sante

    2004-09-01

    The aim of this study is to assess an experimental approach for technological development of a direct compression formulation. A simple formula was considered composed by an active ingredient, a diluent and a lubricant. The active ingredient and diluent were selected as an example according to their typical densification mechanism: the nitrofurantoine, a fragmenting material, and the cellulose microcrystalline (Vivapur), which is a typical visco-elastic material, equally displaying good bind and disintegrant properties. For each ingredient, samples of different particle size distribution were selected. Initially, tabletability of pure materials was studied by a rotary press without magnesium stearate. Vivapur tabletability decreases with increase in particle size. The addition of magnesium stearate as lubricant decreases tabletability of Vivapur of greater particle size, while it kept unmodified that of Vivapur of lower particle size. Differences in tabletability can be related to differences in particle-particle interactions; for Vivapur of higher particle size (Vivapur 200, 102 and 101), the lower surface area develops lower surface available for bonds, while for Vivapur of lower particle size (99 and 105) the greater surface area allows high particle proximity favouring particle cohesivity. Nitrofurantoine shows great differences in compression behaviour according to its particle size distribution. Large crystals show poorer tabletability than fine crystals, further decreased by lubricant addition. The large crystals poor tabletability is due to their poor compactibility, in spite of high compressibility and plastic intrinsic deformability; in fact, in spite of the high densification tendency, the nature of the involved bonds is very weak. Nitrofurantoine samples were then mixed with Vivapurs in different proportions. Compression behaviour of binary mixes (tabletability and compressibility) was then evaluated according to diluents proportion in the mixes. The

  20. Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals.

    PubMed

    Zhu, Yi; Gao, Yong; Tao, Caroline; Shao, Mengle; Zhao, Shangang; Huang, Wei; Yao, Ting; Johnson, Joshua A; Liu, Tiemin; Cypess, Aaron M; Gupta, Olga; Holland, William L; Gupta, Rana K; Spray, David C; Tanowitz, Herbert B; Cao, Lei; Lynes, Matthew D; Tseng, Yu-Hua; Elmquist, Joel K; Williams, Kevin W; Lin, Hua V; Scherer, Philipp E

    2016-09-13

    "Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue. PMID:27626200

  1. A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao).

    PubMed

    Tang, Zheng-Hai; Li, Ting; Tong, Yun-Guang; Chen, Xiao-Jia; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-Jian

    2015-12-01

    Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment. PMID:26695708

  2. Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems.

    PubMed

    Pedraza, Ana; Sicilia, María Dolores; Rubio, Soledad; Pérez-Bendito, Dolores

    2006-01-01

    An aggregation parameter-based methodology for determining acid and neutral drugs in pharmaceutical dosage forms is presented. The method is based on competitive self-assembly in ternary dye-surfactant-drug aqueous mixtures. Dyes bearing charge of opposite sign to that of surfactants bind to surfactant to form mixed dye-surfactant aggregates, which are monitored from changes in the spectra features of the dye. The drug competes with the dye to interact with the surfactant to form drug-surfactant aggregates, which results in a decrease in the surfactant to dye binding degree proportional to the drug concentration in the aqueous solution. Coomassie Brilliant Blue G (CBBG) and didodecyldimethylammonium bromide (DDABr) were the dye and surfactant reactant used, respectively. The suitability of the surfactant to dye binding degree (SDBD) method to determine drugs with very different molecular structure: propionic (flurbiprofen, ibuprofen, naproxen and ketoprofen) and acetic (diclofenac, felbinac and zomepirac) acids, indolines (indomethacin and sulindac), glycyrrhetinic acid derivatives (carbenoxolone and enoxolone), salicylates (diflunisal and phenyl salicylate), oxicams (meloxicam, piroxicam and tenoxicam), pyrazolones (phenylbutazone and sulfinpyrazone) and hydrocortisones (dexamethasone and prednisolone) has been proved. The proposed method was successfully applied to the determination of drugs in commercial formulates (effervescent granulates, tablets, suppositories, gels and blisters) with a minimum sample treatment (dilution of liquid samples and dissolution of solid samples). PMID:16365667

  3. Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids.

    PubMed

    Koluman, Ahmet; Akar, Nejat; Malkan, Umit Y; Haznedaroglu, Ibrahim C

    2016-01-01

    Introduction. Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. Methods. The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. Results. TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. Conclusion. The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies. PMID:26925418

  4. pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin

    PubMed Central

    Wu, Jing-Liang; Tian, Gui-Xiang; Yu, Wen-Jing; Jia, Guang-Tao; Sun, Tong-Yi; Gao, Zhi-Qin

    2016-01-01

    The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid–glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA–GA/HA–His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via 1H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA–GA/HA–His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA–GA/HA–His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA–GA/HA–His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma. PMID:27043540

  5. Role of connexin-43 hemichannels in the pathogenesis of Yersinia enterocolitica.

    PubMed

    Velasquez Almonacid, L A; Tafuri, S; Dipineto, L; Matteoli, G; Fiorillo, E; Della Morte, R; Fioretti, A; Menna, L F; Staiano, N

    2009-12-01

    Connexin (Cx) channels are sites of cytoplasmic communication between contacting cells. Evidence indicates that the opening of hemichannels occurs under both physiological and pathological conditions. In this paper, the involvement of Cx-43 hemichannels is demonstrated in the pathogenesis of Yersinia. Parental HeLa cells and transfected HeLa cells stably expressing Cx-43 (HCx43) were infected with Yersiniaenterocolitica, and bacterial uptake was measured by the colony-forming unit method. Bacterial uptake was higher in HCx43 cells than in parental cells and was inhibited by the Cx channel blocker, 18-alpha-glycyrrhetinic acid (AGA). The inhibitory effect of AGA was more pronounced on the Y. enterocolitica uptake by HCx43 cells than by parental cells. The ability of HCx43 cells to incorporate the permeable fluorescent tracer Lucifer Yellow (LY) was assessed. Dye incorporation was inhibited by AGA, whereas Y. enterocolitica infection of HCx43 cells increased LY incorporation. Western blotting analysis demonstrated that Y. enterocolitica infection of HCx43 cells induced tyrosine phosphorylation of Cx-43, thus supporting a critical role for Cx-43 in the strategies exploited by bacterial pathogens to invade non-phagocytic cells. PMID:18824377

  6. Quantification of Bile Acids in Traditional Animal Medicines and Their Preparations Using Ultra High-Performance Liquid Chromatography-Mass Spectrometry in the Multiple Reaction Monitoring Mode.

    PubMed

    Yerigui; Wu, Xiu-Hong; Wang, Xi-Jun; Ma, Chao-Mei

    2016-01-01

    An ultra-high-performance liquid chromatograph-triple quadrupole mass spectrometry has been established and validated for the simultaneous quantification of 15 bile acids in four traditional animal medicines and their preparations. The separations of bile acids were performed on an Agilent ZORBAX Eclipse XDB-C18 column (50 × 2.1 mm; 1.8 μm) with methanol-0.1% formic acid as the mobile phase. Glycyrrhetinic acid was added as internal standard owing to its similar physiochemical properties with the bile acids. Using this condition, detected in the multiple reaction monitoring mode, the 15 bile acids, including three groups of isomers, were well quantified individually. Method validation showed that the linear regression relationship (r(2), 0.9993 - 0.9999), precisions (intra-day RSD, 0.96 - 4.31%; inter-day, 1.73 - 4.43%), and recovery (95.3 - 120.9%) were all satisfactory. The analysis results showed that bear bile and bezoar (Niu Huang) as well as their formulations contained large amounts of most of the 15 bile acids. In addition, this research revealed for the first time the presences of bile acids in animal waste medication used in traditional medicine from two clinics, Hei-Bing-Pian (discharges of wild boar) and Trogopterus Dung. The established method could be used for the quantification of other bile- or animal waste-based crude drugs and their formulated products. PMID:27169647

  7. Human dehydrogenase/reductase (SDR family) member 11 is a novel type of 17β-hydroxysteroid dehydrogenase.

    PubMed

    Endo, Satoshi; Miyagi, Namiki; Matsunaga, Toshiyuki; Hara, Akira; Ikari, Akira

    2016-03-25

    We report characterization of a member of the short-chain dehydrogenase/reductase superfamily encoded in a human gene, DHRS11. The recombinant protein (DHRS11) efficiently catalyzed the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5α-androstanes into their 17β-hydroxyl metabolites with NADPH as a coenzyme. In contrast, it exhibited reductive 3β-hydroxysteroid dehydrogenase activity toward 5β-androstanes, 5β-pregnanes, 4-pregnenes and bile acids. Additionally, DHRS11 reduced α-dicarbonyls (such as diacetyl and methylglyoxal) and alicyclic ketones (such as 1-indanone and loxoprofen). The enzyme activity was inhibited in a mixed-type manner by flavonoids, and competitively by carbenoxolone, glycyrrhetinic acid, zearalenone, curcumin and flufenamic acid. The expression of DHRS11 mRNA was observed widely in human tissues, most abundantly in testis, small intestine, colon, kidney and cancer cell lines. Thus, DHRS11 represents a novel type of 17β-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution. PMID:26920053

  8. Influence of certain ingredients on the SPF determined in vivo.

    PubMed

    Couteau, Céline; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence J M

    2012-12-01

    When determined in vitro, the SPF of certain commercial sunscreen products can be lower than the SPF indicated on the label. The study of the composition of this type of product enabled us to note that the majority contained substances reputed to have anti-inflammatory properties. This effect is shown by inhibiting the erythema, without protecting the skin, which constitutes a serious public health problem. The anti-inflammatory effects of αbisabolol-, allantoin- and 18-β-glycyrrhetinic acid-based emulsions, as well as commercial sun products containing any one of these molecules, have been tested with phorbol myristate acetate on mice. The effectiveness of these sunscreens products is quantified using two indicators: SPF (sun protection factor) and PF-UVA (protection factor-UVA) by in vitro method. We were thus able to show that certain sun products have an anti-inflammatory effect, which in turn causes the SPF value shown on the product to be overestimated, indeed sometimes by considerably large margins. PMID:22707250

  9. The comparative pharmacokinetics of four bioactive ingredients after administration of Ramulus Cinnamomi-Radix Glycyrrhizae herb pair extract, Ramulus Cinnamomi extract and Radix Glycyrrhizae extract.

    PubMed

    Wang, Shengnan; Sun, Lijiao; Gu, Liqiang; Zhang, Yuanyuan; Zhao, Simin; Zhao, Long-Shan; Bi, Kai-Shun; Chen, Xiaohui

    2016-08-01

    Ramulus Cinnamomi (RC)-Radix Glycyrrhizae (RG) is a classic herb pair, which is commonly used as a fixed form to treat cardiovascular disease in the clinic. Our work aimed to compare the pharmacokinetic difference of cinnamic acid, liquiritin, isoliquiritigenin and glycyrrhetinic acid in rats after oral administration of the RC-RG herb pair extracts [Guizhigancao Decoction (GGD) and Lingguizhugan Decoction (LGZGD)] and the single RC or RG extract. A HPLC-MS method was developed and validated to study comparative pharmacokinetics. The pharmacokinetic parameters (Cmax , AUC, MRT) of four compounds between the RC-RG herb pair group and the single herb (RC or RG) group showed significant differences (p < 0.05). Compared with the single herb (RC or RG) group, higher peak concentration, slower elimination and larger exposure could be observed after giving the RC-RG herb-pair extracts. The pharmacokinetic differences might indicate the relativity of remedy in the RC-RG herb pair and provide scientific information for rational administration of the drug in the clinic. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26694528

  10. Mechanical signaling coordinates the embryonic heartbeat.

    PubMed

    Chiou, Kevin K; Rocks, Jason W; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F; Prosser, Benjamin L; Discher, Dennis E; Liu, Andrea J

    2016-08-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts-consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  11. Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids

    PubMed Central

    Koluman, Ahmet; Akar, Nejat; Malkan, Umit Y.; Haznedaroglu, Ibrahim C.

    2016-01-01

    Introduction. Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. Methods. The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. Results. TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. Conclusion. The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies. PMID:26925418

  12. Roles of phytochemicals in amino acid nutrition.

    PubMed

    Kong, Xiangfeng; Wu, Guoyao; Yin, Yinlong

    2011-01-01

    Chinese herbal medicine (CHM) is often used as dietary supplements to maintain good health in animals and humans. Here, we review the current knowledge about effects of CHM (including ultra-fine Chinese herbal powder, Acanthopanax senticosus extracts, Astragalus polysaccharide, and glycyrrhetinic acid) as dietary additives on physiological and biochemical parameters in pigs, chickens and rodents. Additionally, we propose possible mechanisms for the beneficial effects of CHM on the animals. These mechanisms include (a) increased digestion and absorption of dietary amino acids; (b) altered catabolism of amino acids in the small intestine and other tissues; (c) enhanced synthesis of functional amino acids (e.g., arginine, glutamine and proline) and polyamines; and (d) improved metabolic control of nutrient utilization through cell signaling. Notably, some phytochemicals and glucocorticoids share similarities in structure and physiological actions. New research findings provide a scientific and clinical basis for the use of CHM to improve well-being in livestock species and poultry, while enhancing the efficiency of protein accretion. Results obtained from animal studies also have important implications for human nutrition and health. PMID:21196382

  13. Metabolism of bupropion by baboon hepatic and placental microsomes

    PubMed Central

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB. PMID:21570381

  14. Carbenoxolone induces oxidative stress in liver mitochondria, which is responsible for transition pore opening.

    PubMed

    Salvi, Mauro; Fiore, Cristina; Battaglia, Valentina; Palermo, Mario; Armanini, Decio; Toninello, Antonio

    2005-05-01

    Carbenoxolone (Cbx), a derivative of glycyrrhetinic acid, which has been found to affect mineralocorticoid and glucocorticoid receptors, induces swelling and membrane potential collapse when added to Ca(2+)-loaded liver mitochondria at 10 microM concentrations. These effects are strictly correlated with hydrogen peroxide generation, increase in oxygen uptake, and sulfhydryl and pyridine nucleotide oxidation. Cyclosporin A, bongkrekic acid, and N-ethylmaleimide completely abolish all the above-described effects, suggesting that Cbx can be considered an inducer of mitochondrial permeability transition by means of oxidative stress. Cbx can also trigger the apoptotic pathway because the above events are also correlated with the loss of cytochrome c. These effects are probably related to the conjugated carbonyl oxygen in C-11, which produces reactive oxygen species by interacting with the mitochondrial respiratory chain, mainly at the level of complex I but, most likely, also with complex III. The oxidative stress induced by Cbx, which is responsible for pore opening, excludes that this is related to a genomic effect of the compound. PMID:15677764

  15. Identification of the 11 beta-hydroxysteroid dehydrogenase type 1 mRNA and protein in human mononuclear leukocytes.

    PubMed

    Fiore, C; Nardi, A; Dalla Valle, L; Pellati, D; Krozowski, Z; Colombo, L; Armanini, D

    2009-10-01

    The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the interconversion between inactive 11-ketoglucocorticoids and their active 11beta-hydroxy derivatives, such as cortisol and corticosterone. We have investigated the expression of 11beta-HSD1 in freshly isolated human peripheral mononuclear leukocytes (MNL). The presence of 11beta-HSD1 mRNA was demonstrated in total RNA by RT-PCR using specific primers designed on the 4th and 5th exons of the human 11beta-HSD1 gene. Fragments of the expected size were consistently detected on agarose gels, and sequencing showed complete identity with the corresponding sequence deposited in GenBank. The occurrence of 11beta-HSD1 protein was established by Western immunoblot analysis with a specific polyclonal antibody. Enzyme oxo-reductase activity was investigated by incubating 12 samples of MNL isolated from from 8 subjects with [3H]cortisone and formation of cortisol was established only in 4 subjects (yield range: 0.15-1.3%) after acetylation and TLC, blank subtraction and correction for losses. 18beta-Glycyrrhetinic acid, an inhibitor of 11 beta-HSD1, reduced cortisol production below detection limit. Dehydrogenase activity could not be demonstrated. It is suggested that, although enzyme activity of 11beta-HSD1 in circulating MNL is low, it is apparently ready for enhancement after MNL migration to sites of inflammation. PMID:19235128

  16. [comparisons of pharmacokinetic profile of eleven bioactive components in Haizao Yuhu decoction modified with Haizao and Gancao anti-drug pair in normal rats].

    PubMed

    Zhang, Yang; Qian, Da-wei; Pan, Ying; Zhai, Yan-juan; Zhou, Xue-ping; Zhong, Gan-sheng; Zhu, Zhen-hua; Duan, Jin-ao

    2015-12-01

    Haizao Yuhu decoction (HYD) is a formula that has been used for approximately 500 years and famous for its efficiency in treating thyroid-related diseases in traditional Chinese medicine (TCM). HYD was first presented by Chen Shi-gong in a famous surgical monograph named Waike Zhengzong during the Ming Dynasty. We conducted the research to investigate the possible pharmacokinetic profile of different prescriptions of HYD in rats, in order to reveal the interactions of Haizao and Gancao drug pair with other herbs in HYD. Liquiritin, naringin, besperidin, peimine, peiminine liquiritigenin, glycyrrhizic acid, hergapten, nobiletin, osthole, glycyrrhetinic acid in blood samples were determined by UPLC-MS/MS. The result revealed tbat Haizao could enhance the peak concentration of glycyrrhizic acid. The other herbs in HYD may promote'the absorption of flavonoids in Gancao in normal rats, but inhibit the absorption of saponins and accelerate their metabolism. Gancao and Haizao drug pair could enhance the bioavailability of hesperidin, peimine, bergapten, nobiletin and osthole and prolong the elimination of peimine and naringin. PMID:27141682

  17. Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

    PubMed Central

    Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Li, Yingchun; Han, Jiang; Zhang, Zhiping

    2013-01-01

    Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. PMID:24232303

  18. Design and synthesis of dual-ligand modified chitosan as a liver targeting vector.

    PubMed

    Chen, Houxiang; Li, Min; Wan, Tao; Zheng, Qichang; Cheng, Mingrong; Huang, Shiqi; Wang, Yong

    2012-02-01

    Vector plays an important role in hepatic targeted drug delivery system. In this study, a novel material as a liver targeting vector, dual-ligand modified chitosan (GCGA) composed of chitosan (CTS), glycyrrhetinic acid (GA) and lactobionic acid (LA), was designed and synthesized by an orthogonal experiment with two-step synthesis under mild conditions. The synthesized final product was characterized and confirmed by FTIR and (1)H-NMR spectroscopy, and DS of GA and LA in CTS were measured to be 13.77 and 16.74 mol% using (1)H-NMR, respectively. The cytotoxicity of CTS and GCGA was concentration dependent which was inverse proportion to the cell viability by MTT assay using L929 cell line, and inhibitory concentration 50% (IC50) was 0.2 mg/ml for GCGA. The in vitro targeting efficiency and the in vitro cellular uptake were investigated. Compared with CTS NPs and GA-CTS NPs, GCGA NPs showed good cell specificity to BEL-7402 cells via the dual-ligand-receptor-mediated recognition, leading to a higher affinity to BEL-7402 cells. The results suggested that GCGA described here has the potential to be used as an effective vector for hepatic targeted drug therapy. PMID:22105225

  19. Kinetics and mechanism of intercellular ice propagation in a micropatterned tissue construct.

    PubMed Central

    Irimia, Daniel; Karlsson, Jens O M

    2002-01-01

    Understanding the effects of cell-cell interaction on intracellular ice formation (IIF) is required to design optimized protocols for cryopreservation of tissue. To determine the effects of cell-cell interactions during tissue freezing, without confounding effects from uncontrolled factors (such as time in culture, cell geometry, and cell-substrate interactions), HepG2 cells were cultured in pairs on glass coverslips micropatterned with polyethylene glycol disilane, such that each cell interacted with exactly one adjacent cell. Assuming the cell pair to be a finite state system, being either in an unfrozen state (no ice in either cell), a singlet state (IIF in one cell only), or a doublet state (IIF in both cells), the kinetics of state transitions were theoretically modeled and cryomicroscopically measured. The rate of intercellular ice propagation, estimated from the measured singlet state probability, increased in the first 24 h of culture and remained steady thereafter. In cell pairs cultured for 24 h and treated with the gap junction blocker 18beta-glycyrrhetinic acid before freezing, the intercellular ice propagation rate was lower than in untreated controls (p < 0.001), but significantly greater than zero (p < 0.0001). These results suggest that gap junctions mediate some, but not all, mechanisms of ice propagation in tissue. PMID:11916845

  20. Kinetics and mechanism of intercellular ice propagation in a micropatterned tissue construct.

    PubMed

    Irimia, Daniel; Karlsson, Jens O M

    2002-04-01

    Understanding the effects of cell-cell interaction on intracellular ice formation (IIF) is required to design optimized protocols for cryopreservation of tissue. To determine the effects of cell-cell interactions during tissue freezing, without confounding effects from uncontrolled factors (such as time in culture, cell geometry, and cell-substrate interactions), HepG2 cells were cultured in pairs on glass coverslips micropatterned with polyethylene glycol disilane, such that each cell interacted with exactly one adjacent cell. Assuming the cell pair to be a finite state system, being either in an unfrozen state (no ice in either cell), a singlet state (IIF in one cell only), or a doublet state (IIF in both cells), the kinetics of state transitions were theoretically modeled and cryomicroscopically measured. The rate of intercellular ice propagation, estimated from the measured singlet state probability, increased in the first 24 h of culture and remained steady thereafter. In cell pairs cultured for 24 h and treated with the gap junction blocker 18beta-glycyrrhetinic acid before freezing, the intercellular ice propagation rate was lower than in untreated controls (p < 0.001), but significantly greater than zero (p < 0.0001). These results suggest that gap junctions mediate some, but not all, mechanisms of ice propagation in tissue. PMID:11916845

  1. Shieldable tumor targeting based on pH responsive self-assembly/disassembly of gold nanoparticles.

    PubMed

    Tian, Zhiqing; Yang, Chengling; Wang, Wei; Yuan, Zhi

    2014-10-22

    A new approach to shield/deshield ligands for controllable tumor targeting was reported, which was based on amphiphilic self-assembly and disassembly of gold nanoparticles (Au NPs). Thanks to the excellent pH response of the system, glycyrrhetinic acid (GA) ligands can be buried inside the Au NPs' assembly at normal tissue pH (pH 7.4), while exposed when the nanostructure is disassembled at tumor extracellular pH (pHe 6.8). Hydrophobic GA molecules not only acted as ligands targeting tumor cells but also provided the major interparticle attractive force for Au NPs' assembling. An ordered assembly of Au NPs with regular shape, proper size and ultrasharp pH sensitivity (ΔpH ∼ 0.2) was achieved by fine-tuning of materials modified on Au NPs. Mechanism studies for assembly and disassembly of Au NPs indicated the possibility of a GA shield when the assembly formed, which was further demonstrated by bovine serum albumin absorption and cellular uptake. The assembly/disassembly process was reversible within extrinsic pH changes, which provides a perspective for reversible tumor targeting. PMID:25233129

  2. Structural and functional changes in gap junctional intercellular communication in a rat model of overactive bladder syndrome induced by partial bladder outlet obstruction

    PubMed Central

    ZHOU, FENGHAI; LI, HAIYUAN; ZHOU, CHUAN; LV, HAIDI; MA, YULEI; WANG, YANGMIN; SONG, BO

    2016-01-01

    The aim of the present study was to investigate the association between connexin (Cx)43 levels and alterations in gap junctional mediation of intercellular communication in overactive bladder syndrome (OAB), and to examine the effects of connexin inhibitor on this condition. Adult female Wistar rats with OAB following partial bladder outlet obstruction (PBBO) (OAB group, n=37) and sham-operated rats (control group, n=17) were studied. The ultrastructure of the rat detrusor was observed by transmission electron microscopy and the protein expression levels of Cx43 were analyzed using western blot analysis. Furthermore, bladder detrusor cells in both groups were cultured and cells in the OAB group were randomly divided into ten groups. In nine of these groups, 18-β glycyrrhetinic acid (18β-GA) was administered at various doses and durations. All groups were compared using fluorescence redistribution after photobleaching and a laser scanning confocal microscope. Cystometry demonstrated that gap junctions were an abundant mechanism among adjacent cells, and Cx43 protein expression levels were increased in the OAB group following 6 weeks of obstruction, as compared with the control group. Mean fluorescence recovery rates in the OAB group were significantly increased, as compared with the control group (P<0.01). Mean fluorescence recovery rates were noted following 18β-GA administration. These results suggested that upregulation of Cx43 induces structural and functional alterations in gap junctional intercellular communication following PBOO, and connexin inhibitors may be a novel therapeutic strategy for the clinical treatment of OAB. PMID:27284295

  3. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation.

    PubMed

    Andrikopoulos, Nikolaos K; Kaliora, Andriana C; Assimopoulou, Andreana N; Papapeorgiou, Vassilios P

    2003-05-01

    Naturally occurring gums and resins with beneficial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper-induced LDL oxidation in vitro. Chiosmastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure-activity relationship showed that the total mastic essential oil, collofonium-like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin 'liquid collection', P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%-78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18-a-glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%-78.8% and 27.0%-64.1% LDL protective activity, respectively. The combination effects (68.7%-76.2% LDL protection) of ursolic-, oleanolic- and ursodeoxycholic- acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses. PMID:12748987

  4. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    NASA Astrophysics Data System (ADS)

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures.

  5. Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

    PubMed Central

    Varshosaz, Jaleh; Hajhashemi, Valiollah; Soltanzadeh, Sindokht

    2011-01-01

    Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs). The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs). LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model. PMID:22175029

  6. Biochemistry of high stearic sunflower, a new source of saturated fats.

    PubMed

    Salas, Joaquín J; Martínez-Force, Enrique; Harwood, John L; Venegas-Calerón, Mónica; Aznar-Moreno, Jose Antonio; Moreno-Pérez, Antonio J; Ruíz-López, Noemí; Serrano-Vega, María J; Graham, Ian A; Mullen, Robert T; Garcés, Rafael

    2014-07-01

    Fats based on stearic acid could be a healthier alternative to existing oils especially hydrogenated fractions of oils or palm, but only a few non-tropical species produce oils with these characteristics. In this regard, newly developed high stearic oil seed crops could be a future source of fats and hard stocks rich in stearic and oleic fatty acids. These oil crops have been obtained either by breeding and mutagenesis or by suppression of desaturases using RNA interference. The present review depicts the molecular and biochemical bases for the accumulation of stearic acid in sunflower. Moreover, aspects limiting the accumulation of stearate in the seeds of this species are reviewed. This included data obtained from the characterization of genes and enzymes related to fatty acid biosynthesis and triacylglycerol assembly. Future improvements and uses of these oils are also discussed. PMID:24858414

  7. Surface properties of superfine alumina trihydrate after surface modification with stearic acid

    NASA Astrophysics Data System (ADS)

    Liu, Gui-hua; Zhou, Bo-hao; Li, Yun-feng; Qi, Tian-gui; Li, Xiao-bin

    2015-05-01

    The surface properties of superfine alumina trihydrate (ATH) after surface modification were studied by measuring the contact angle, active ratio, oil adsorption, total organic carbon, adsorption ratio, and Fourier transform infrared (FTIR) spectrum. The contact angle increased initially and then slowly decreased with an increase of the amount of stearic acid. However, the surface free energy decreased initially and then increased. Surface modification with stearic acid or sodium stearate can benefit from elevating temperature. The base surface tension component and the free energy of Lewis acid-base both declined sharply following the surface modification. Excess stearic acid was physically adsorbed in the form of multilayer adsorption, and an interaction between oxygen on the ATH surface and hydroxyl in stearic acid was subsequently determined. Our results further indicated that the contact angle and adsorption ratio can be used as control indicators for surface modification compared with active ratio, oil adsorption and total organic carbon.

  8. Intrinsic adhesion force of lubricants to steel surface.

    PubMed

    Lee, Jonghwi

    2004-09-01

    The intrinsic adhesion forces of lubricants and other pharmaceutical materials to a steel surface were quantitatively compared using Atomic Force Microscopy (AFM). A steel sphere was attached to the tip of an AFM cantilever, and its adhesion forces to the substrate surfaces of magnesium stearate, sodium stearyl fumarate, lactose, 4-acetamidophenol, and naproxen were measured. Surface roughness varied by an order of magnitude among the materials. However, the results clearly showed that the two lubricants had about half the intrinsic adhesion force as lactose, 4-acetamidophenol, and naproxen. Differences in the intrinsic adhesion forces of the two lubricants were insignificant. The lubricant molecules were unable to cover the steel surface during AFM measurements. Intrinsic adhesion force can slightly be modified by surface treatment and compaction, and its tip-to-tip variation was not greater than its difference between lubricants and other pharmaceutical particles. This study provides a quantitative fundamental basis for understanding adhesion related issues. PMID:15295791

  9. Fabrication of a superhydrophobic surface on a wood substrate

    NASA Astrophysics Data System (ADS)

    Wang, Shuliang; Shi, Junyou; Liu, Changyu; Xie, Cheng; Wang, Chengyu

    2011-09-01

    A layer of lamellar superhydrophobic coating was fabricated on a wood surface through a wet chemical process. The superhydrophobic property of the wood surface was measured by contact angle (CA) measurements. The microstructure and chemical composition of the superhydrophobic coating were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). An analytical characterization revealed that the microscale roughness of the lamellar particles was uniformly distributed on the wood surface and that a zinc stearate monolayer (with the hydrophobic groups oriented outward) formed on the ZnO surface as the result of the reaction between stearic acid and ZnO. This process transformed the wood surface from hydrophilic to superhydrophobic: the water contact angle of the surface was 151°, and the sliding angle was less than 5°.

  10. Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for improvement of oral bioavailability in treatment of hypertension: polyethylene glycol versus chitosan oligosaccharide lactate.

    PubMed

    Üstündağ-Okur, Neslihan; Yurdasiper, Aysu; Gündoğdu, Evren; Gökçe, Evren Homan

    2016-02-01

    Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG) stearate for improvement of its oral bioavailability. Compritol, poloxamer and lecithin were used for the preparation of SLNs by homogenisation method. After in vitro characterisation effect of lipase, pepsin, or pancreatin on degradation and release rate were investigated. Cytotoxicity and permeation were studied on Caco-2 cells. As COL concentration increased in SLNs, size and zeta potential increased. PEG concentration was reversely proportional to particle size with no change in zeta potential. Encapsulation efficiencies (EEs) were determined as 84-98%. DSC confirmed solubilisation of NB in lipid matrix. A sustained release with no burst effect was determined. The presence of enzymes affected the release. SLNs did not reveal cytotoxicity and highest permeability was obtained with PEG modification. PEG-modified SLNs could be offered as a promising strategy for oral delivery of NB. PMID:26444187

  11. Improving aerosolization of drug powders by reducing powder intrinsic cohesion via a mechanical dry coating approach.

    PubMed

    Zhou, Qi Tony; Qu, Li; Larson, Ian; Stewart, Peter J; Morton, David A V

    2010-07-15

    The aim of this study was to investigate the effect of coating on the aerosolization of three model micronized powders. Three model powder materials (salbutamol sulphate, salmeterol xinafoate, triamcinolone acetonide) were chosen not only for their different chemical properties but also for their different physical properties such as shape and size distribution. Each powder was coated with 5% (w/w) magnesium stearate using two different dry mechanofusion approaches. After mechanofusion, both poured and tapped densities for all three model drug powders significantly increased. There were significant improvements in aerosolization behavior from an inhaler device for all model powders after mechanofusion. Such improvements in aerosolization were attributed to the reduction in agglomerate strength caused by decreasing powder intrinsic cohesion via surface modification. The work also indicated that the effect of the coating was dependant on the initial particle properties. PMID:20435112

  12. [Determination of contact angle of pharmaceutical excipients and regulating effect of surfactants on their wettability].

    PubMed

    Hua, Dong-dong; Li, He-ran; Yang, Bai-xue; Song, Li-na; Liu, Tiao-tiao; Cong, Yu-tang; Li, San-ming

    2015-10-01

    To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose stearate. In addition, surfactants both in droplets and mixed in excipients significantly reduced the contact angle of excipients, and their abilities to lower contact angle varied. The results of the present study offer a guideline in the formulation design of tablets. PMID:26837184

  13. Etofenamate fatty acid asters. An example of a new route of drug metabolism.

    PubMed

    Dell, H D; Fielder, J; Kamp, R; Gau, W; Kurz, J; Weber, B; Wuensche, C

    1982-01-01

    Etofenamate [2-(2-hydroxyethoxy)ethyl-N-(alpha, alpha, alpha-trifluoro-m-tolyl)-anthranilate] was administered to dogs by the oral route. Minor amounts of etofenamate (Eto) and its glucuronide were found in urine and feces. The main portion of metabolites was eliminated as flufenamic acid (Flu) and hydroxy derivatives of Eto and Flu. Furthermore, a highly lipophilic fraction was isolated (extraction and TLC) and further separated into several compounds (HPLC, GLC). These metabolites were identified as Eto oleate, palmitate, linoleate, stearate, palmitoleate, myristate, and laurate by NMR and MS. The structures were confirmed by comparison with authentic material. The conjugation of etofenamate with fatty acids is an example of a new route of drug metabolism. PMID:6124384

  14. Design of Peumus boldus tablets by direct compression using a novel dry plant extract.

    PubMed

    Palma, Santiago; Luján, Claudia; Llabot, Juan Manuel; Barboza, Gloria; Manzo, Ruben Hilario; Allemandi, Daniel Alberto

    2002-02-21

    A solid pharmaceutical dosage formulation using a novel dry plant extract of Peumus boldus MOL. (Monimiaceae) (Pb) is proposed. The botanical evaluation of plant material, through morphological and anatomical diagnosis, is presented. This evaluation permits to identify the herb to be used correctly. The analysis of the most extractive solvent mixture and the attainment of plant extract (fluid and dry) are reported. Several formulations (tablets) containing a novel dry plant extract of Pb and common excipients for direct compression are evaluated. The following formulation: dry plant extract of Pb (170 mg), Avicel PH101 (112 mg), Lactose CD (112) and magnesium stearate (6 mg), compressed at 1000 mPa, showed the best pharmaceutical performance. PMID:11897423

  15. Water dispersible Fe3O4 nanoparticles carrying doxorubicin for cancer therapy.

    PubMed

    Jayakumar, Onattu Damodharan; Ganguly, Rajib; Tyagi, Avesh Kumar; Chandrasekharan, Dhanya K; Nair, Cherupally K Krishnan

    2009-11-01

    Water dispersible Fe3O4 nanoparticles (coated with Poly Vinyl Pyrolidone (PVP) and Poly oxy ethylene 25-propylene glycol stearate (POES)) and complexed with Doxorubicin has been prepared and characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The antitumor activity of these particles has been studied by targeting the complex to the tumor site, using an externally applied magnetic field, after oral administration of the magnetic nanoparticle-drug complexes. Our results reveal that the chemotherapy effect of Doxorubicin could be considerably enhanced by combination of the application of the drug-conjugated magnetic Fe3O4 nanoparticles, which are biocompatible and stable, and targeted drug delivery with a magnet. The present report provides the first evidence for the promising application of this novel approach with PVP coated Fe3O4 nanoparticles for cancer therapy using an in vivo murine model. PMID:19908532

  16. Controlled complexation of plasmid DNA with cationic polymers: effect of surfactant on the complexation and stability of the complexes.

    PubMed

    Ikonen, Marjukka; Murtomäki, Lasse; Kontturi, Kyösti

    2008-10-01

    The aggregation of the cationic polymer-plasmid DNA complexes of two commonly used polymers, polyethyleneimine (PEI) and poly-l-lysine (PLL) were systematically compared. The complexation was studied in 5% glucose solution at 25 degrees C using dynamic light scattering and isothermal titration calorimetry. The aggregation of the complexes was controlled by addition of the surfactant polyoxyethylene stearate (POES). The stability of the complexes was evaluated using dextran sulphate (DS) as relaxing agent. The relaxation of the complexes in the presence of DS was studied using agarose gel electrophoresis. This study elucidates the role of surfactant in controlling the size of the PEI/pDNA complex and reveals the differences of the two polymers as complexing agents. PMID:18583110

  17. Mechanistic studies on aggregation of polyethylenimine-DNA complexes and its prevention.

    PubMed

    Sharma, Vikas K; Thomas, Mini; Klibanov, Alexander M

    2005-06-01

    Aggregation of polyethylenimine (PEI)-DNA complexes severely undermines their utility for gene delivery into mammalian cells. Herein we undertook to elucidate the mechanism of this deleterious phenomenon and to develop rational strategies for its prevention. The effect of temperature, surfactants, complex concentration, ionic strength, viscosity, and pH on the time course of this aggregation was systematically examined. The aggregation process was completely inhibited by 2.5% polyoxyethylene (100) stearate (POES) and to a lesser degree by other nonionic surfactants. Importantly, POES preserved the transfection efficiency of the complexes without inducing toxicity. The aggregation was also reduced by lowering the temperature and pH, diluting the complexes, and increasing the solution viscosity. It is concluded that PEI-DNA complexes aggregate primarily due to hydrophobic interactions, while electrostatic attractions play little role. PMID:15818564

  18. Equilibrium Potentials of Membrane Electrodes

    PubMed Central

    Wang, Jui H.; Copeland, Eva

    1973-01-01

    A simple thermodynamic theory of the equilibrium potentials of membrane electrodes is formulated and applied to the glass electrode for measurement of pH. The new formulation assumes the selective adsorption or binding of specific ions on the surface of the membrane which may or may not be permeable to the ion, and includes the conventional derivation based on reversible ion transport across membranes as a special case. To test the theory, a platinum wire was coated with a mixture of stearic acid and methyl-tri-n-octyl-ammonium stearate. When this coated electrode was immersed in aqueous phosphate solution, its potential was found to be a linear function of pH from pH 2 to 12 with a slope equal to the theoretical value of 59.0 mV per pH unit at 24°. PMID:4516194

  19. Thermodynamics of binding water and solute to powdered long-chain salts of fatty acids.

    PubMed

    Mahapatra, P K; Chattoraj, D K

    1994-10-01

    Hydration of powdered fatty acids and their salts has been studied both in presence and absence of neutral salts, sucrose and urea using the isopiestic vapour pressure technique. Moles of water vapour adsorbed per mole or kg of soaps like sodium palmitate, sodium stearate, sodium myristate and sodium laurate have been measured in presence and absence of salts and compared with that of detergents (SDS, CTAB, DTAB and MTAB). For each case of positive excess adsorption of water vapour and negative excess adsorption of inorganic salts, urea and sucrose to different soaps, the standard free energy change (delta G degrees) per kg of substrate in bringing the bulk mole fraction from zero to unity have been calculated using an appropriate thermodynamic equation and the values so obtained have been compared critically. PMID:7851944

  20. A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride.

    PubMed

    Mužíková, Jitka; Kubíčková, Alena

    2016-09-01

    The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders. PMID:27383891

  1. Gas chromatography with tandem differential mobility spectrometry of fatty acid alkyl esters and the selective detection of methyl linolenate in biodiesels by dual-stage ion filtering.

    PubMed

    Pasupuleti, D; Pierce, K; Eiceman, G A

    2015-11-20

    Alkyl esters of fatty acids (FAAEs) with carbon numbers from 8 to 20 formed protonated monomers and proton bound dimers through atmospheric pressure chemical ionization reactions and these gas ions were characterized for their field dependent mobility coefficients using differential mobility spectrometry (DMS). Separation of ion peaks with a vapor modifier was achieved for ions with masses of 317-1033 Da though the differences in these coefficients and the resolution of ion peaks decreased proportionally with increased ion mass. Differences in dispersion curves were sufficient to isolate ions from specific FAAEs in the effluent of a gas chromatograph by dual stage ion filtering using a tandem DMS detector. Methyl linolenate was isolated from nearby eluting methyl oleate, methyl stearate and methyl linoleate within analysis times of 10s without measureable complications from charge suppression in the ion source or leakage in filtering of ions with close proximity of dispersion behavior. PMID:26427321

  2. Solvothermal synthesis of gallium-doped zinc oxide nanoparticles with tunable infrared absorption

    NASA Astrophysics Data System (ADS)

    Zhou, Haifeng; Wang, Hua; Tian, Xingyou; Zheng, Kang; Xu, Fei; Su, Zheng; Tian, Konghu; li, Qiulong; Fang, Fei

    2014-12-01

    The doping of ZnO nanoparticles (NPs) has been attracting a lot of attention both for fundamental studies and potential applications. In this manuscript, we report the preparation of gallium doped zinc oxide (GZO) NPs through the solvothermal method. In order to obtain the effective Ga doping in the ZnO crystalline lattice, we identified the optimal reaction conditions in terms of different Zn precursors, temperature, and heating rate. The results show that GZO NPs with tunable infrared absorption can be received using different molar ratios of Ga(NO3)3 and zinc stearate (Zn[CH3(CH2)16COO]2, ZnSt2) kept in the sealed autoclaves at 160 °C for 8 h. Furthermore, the growth of the GZO NPs was investigated by monitoring the optical absorption spectral and the corresponding chemical composition of aliquots extracted at different reaction time intervals.

  3. The influence of inner hydrophobisation on water transport properties of modified lime plasters

    NASA Astrophysics Data System (ADS)

    Pavlíková, Milena; Pavlík, Zbyšek; Pernicová, Radka; Černý, Robert

    2016-06-01

    The effect of hydrophobic agent admixture on water vapour and liquid water transport properties of newly designed lime plasters is analysed in the paper. The major part of physico - chemical building deterioration is related to the penetration of moisture and soluble salts into the building structure. For that reason, the modified lime plasters were in the broad range of basic material properties tested. From the quantitative point of view, the measured results clearly demonstrate the big differences in the behaviour of studied materials depending on applied modifying admixtures. From the practical point of view, plaster made of lime hydrate, metakaolin, zinc stearate and air-entraining agent can be recommended for renovation purposes. The accessed material parameters will be used as input data for computational modelling of moisture transport in this type of porous building materials and will be stored in material database.

  4. Self-assembled biomimetic superhydrophobic CaCO3 coating inspired from fouling mineralization in geothermal water.

    PubMed

    Wang, Gong G; Zhu, Li Q; Liu, Hui C; Li, Wei P

    2011-10-18

    Inspired from fouling self-mineralization in geothermal water, a novel biomimetic cactuslike CaCO(3) coating with superhydrophobic features is reported in this letter. The structure, morphologies, and phases of the CaCO(3) coating were characterized by X-ray diffractometry, scanning electron microscopy, transmission electron microscopy, and infrared spectrophotometry. After prenucleation treatment, a continuous cactuslike CaCO(3) coating with hierarchical nano- and microstructures was self-assembled on stainless steel surfaces after immersion in simulated geothermal water at 50 °C for 48 h. After being modified with a low-surface-energy monolayer of sodium stearate, the as-prepared coating exhibited superhydrophobic properties with a water contact angle of 158.9° and a sliding angle of 2°. Therefore, this work might open up a new application field of geothermal resources and provide insight into designing multidimensional structures with functional applications, including superhydrophobic surfaces. PMID:21919516

  5. Precipitation and Solubility of Calcium Soaps in Basic Aqueous Media.

    PubMed

    Beneventi, Davide; Carré, Bruno; Gandini, Alessandro

    2001-05-01

    Measurements of the surface tension of aqueous media containing calcium salts of different fatty acids, whose structure only varied by the number of C=C unsaturations along their aliphatic chains, showed that their solubility increased as a function of this parameter going from near zero for calcium stearate to 4x10(-4) mol l(-1) for the linolenate homologue. The solubility product of the calcium soap corresponding to each tested fatty acid was estimated by using the anionic fatty acids adsorption isotherms in order to obtain the amount of dissolved ionic fatty acid at increasing concentration of calcium ions. These findings are discussed in terms of their serious repercussions on the operations related to flotation deinking in waste paper recycling. Copyright 2001 Academic Press. PMID:11334526

  6. The Prevention of the Ice Hazard on Airplanes

    NASA Technical Reports Server (NTRS)

    Geer, William C; Scott, Merit

    1930-01-01

    A review of various methods to prevent ice formation and adhesion to aircraft surfaces is given. It was concluded that the adhesion of ice to a surface may be reduced somewhat by the application of certain waxes and varnishes. In the experiments described, the varnishes containing calcium stearate and calcium oleate gave the best results. In wind tunnel tests, the adhesion was further reduced by the application of these waxes and varnishes to a thin, heat insulating layer of rubber. The adhesion of ice is greatly reduced when the surface consists of a vehicle which carries an oil in sufficient quantity so that the surface of the vehicle is self lubricating. Ice may be removed from wings, struts, wires and other parts of an airplane during flight by the inflation of properly constructed pneumatic rubber members, providing that these members have been previously treated with a suitable low adhesion oil.

  7. Facile Phosphine-Free Synthesis of CdSe/ZnS Core/Shell Nanocrystals Without Precursor Injection

    NASA Astrophysics Data System (ADS)

    Zhu, Chang-Qing; Wang, Peng; Wang, Xin; Li, Yan

    2008-06-01

    A new simple method for synthesis of core/shell CdSe/ZnS nanocrystals (NCs) is present. By adapting the use of cadmium stearate, oleylamine, and paraffin liquid to a non-injection synthesis and by applying a subsequent ZnS shelling procedure to CdSe NCs cores using Zinc acetate dihydrate and sulfur powder, luminescent CdSe/ZnS NCs with quantum yields of up to 36% (FWHM 42 43 nm) were obtained. A seeding-growth technique was first applied to the controlled synthesis of ZnS shell. This method has several attractive features, such as the usage of low-cost, green, and environmentally friendlier reagents and elimination of the need for air-sensitive, toxic, and expensive phosphines solvent. Furthermore, due to one-pot synthetic route for CdSe/ZnS NCs, the approach presented herein is accessible to a mass production of these NCs.

  8. In vitro and in vivo evaluation of oral tablet formulations prepared with ketoconazole and hydroxypropyl-beta-cyclodextrin.

    PubMed

    Taneri, Filiz; Ozcan, Ipek; Guneri, Tamer

    2010-04-01

    The objective of this study was to enhance the solubility, dissolution rate, and oral bioavailability of a very poorly water-soluble anti-fungal agent, ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin derivative, hydroxypropyl-beta cyclodextrin (HP-beta-CD). Two groups of tablets containing KET alone and KET:HP-beta-CD (1:2) kneaded product (KP) including magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were prepared by direct compression method. After the characterization studies, the in vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out. To evaluate the in vivo bioavailability, the tablets were administered orally to rabbits and drug levels in serum were determined by HPLC. Tablets containing the cyclodextrin complex showed a higher in vitro dissolution rate and bioavailability compared to the tablets containing KET alone. PMID:20148713

  9. Experimental designs dedicated to the evaluation of a membrane extraction method: membrane-assisted solvent extraction for compounds having different polarities by means of gas chromatography-mass detection.

    PubMed

    Vincelet, Carole; Roussel, Jean Marc; Benanou, David

    2010-03-01

    Membrane-assisted solvent extraction was applied for the determination of different classes of compounds in water, having K(o/w) (octanol-water partition coefficient) values between 10(1) (aniline) and 10(8) (methyl stearate), by means of experimental designs. Four solvents were investigated--propan-2-ol, ethyl acetate, diisopropyl ether and cyclohexane--as well as extraction time, temperature, salt impact, pH and methanol addition. The best choice was diisopropyl ether, 50 degrees C, 30 min and an addition of 3 g of sodium chloride at pH 2 for polar compounds. The relative standard deviation (n = 3) was found in the range from 5 to 17%. Recoveries ranged between 34 and 100%. Membrane-assisted solvent extraction was successfully applied to a fast screening method dedicated to an unknown wastewater sample. PMID:20127320

  10. One-pot process combining transesterification and selective hydrogenation for biodiesel production from starting material of high degree of unsaturation.

    PubMed

    Yang, Ru; Su, Mengxing; Li, Min; Zhang, Jianchun; Hao, Xinmin; Zhang, Hua

    2010-08-01

    A one-pot process combining transesterification and selective hydrogenation was established to produce biodiesel from hemp (Cannabis sativa L.) seed oil which is eliminated as a potential feedstock by a specification of iodine value (IV; 120 g I(2)/100g maximum) contained in EN 14214. A series of alkaline earth metal oxides and alkaline earth metal supported copper oxide were prepared and tested as catalysts. SrO supported 10 wt.% CuO showed the superior catalytic activity for transesterification with a biodiesel yield of 96% and hydrogenation with a reduced iodine value of 113 and also exhibited a promising selectivity for eliminating methyl linolenate and increasing methyl oleate without rising methyl stearate in the selective hydrogenation. The fuel properties of the selective hydrogenated methyl esters are within biodiesel specifications. Furthermore, cetane numbers and iodine values were well correlated with the compositions of the hydrogenated methyl esters according to degrees of unsaturation. PMID:20231090

  11. Influence of the ester chain length on the mesogenic behavior and optical anisotropy of 4-[[4-(butoxy)phenyl]diazenyl]phenyl alkanoates

    NASA Astrophysics Data System (ADS)

    Niezgoda, Izabela; Szypszak, Ewelina; Dardas, Dorota; Galewski, Zbigniew

    2016-04-01

    In this manuscript, we report synthesis and physico-chemical characterization of 4-[[4-(butoxy)phenyl]diazenyl]phenyl alkanoates homologous series. For the first time, nineteen derivatives are described here. The enantiotropic nematic phase is typically observed among all members of this series. However, in the case of 4-[[4-(butoxy)phenyl]diazenyl]phenyl stearate, the nematic phase shows a monotropic character. In addition to liquid-crystalline polymorphism, a second crystalline form was observed in some homologs. Furthermore, using a photoelastic modulator, the optical anisotropy in the nematic phase was determined in the first nine compounds of this series. Temperature dependence of optical anisotropy at significantly lower values of reduced temperature is relatively weak. In contrast, optical anisotropy shows a strong temperature effect near isotropization. Moreover, the influence of the ester chain elongation on liquid crystalline and optical properties was established.

  12. Intramolecular Entropy and Size-Dependent Solution Properties of Nanocrystal-Ligands Complexes.

    PubMed

    Yang, Yu; Qin, Haiyan; Peng, Xiaogang

    2016-04-13

    CdSe-stearates nanocrystal-ligands complex as a whole possess strongly temperature- and size-dependent yet well-defined solubility in small organic solvents, which shows little solvent effects as long as the complexes remained intact. A quantitative thermodynamic model is developed to describe such solubility behavior, which differs fundamentally from conventional models for micron colloids. The model reveals that the conformation entropy of the n-alkanoate chain released in dissolution greatly stabilize the colloidal solution but the strong chain-chain interdigitation between adjacent particles in solid diminishes the solubility. These understandings result in "entropic ligands" (see full disclosure in another report (10.1021/acs.nanolett.6b00730)) as the universal means to battle processability challenges of colloidal nanocrystals. PMID:26923516

  13. [Studies on the constituents of trichosanthes root. III. Constituents of roots of Trichosanthes bracteata Voigt].

    PubMed

    Kitajima, J; Mukai, A; Masuda, Y; Tanaka, Y

    1989-04-01

    From the fresh roots of Trichosanthes bracteata Voigt., the following substances were identified: methyl palmitate, palmitic acid, suberic acid, alpha-spinasterol, stigmast-7-en-3 beta-ol, alpha-spinasterol 3-O-beta-D-glucopyranoside, stigmast-7-en-3 beta-ol 3-O-beta-D-glucopyranoside, glyceryl 1-palmitate, glyceryl 1-stearate, bryonolic acid, cucurbitacin B, isocucurbitacin B, 3-epi-isocucurbitacin B, 23,24-dihydrocucurbitacin B, 23,24-dihydroisocucurbitacin B, 23,24-dihydro-3-epi-isocucurbitacin B, cucurbitacin D, isocucurbitacin D and D-glucose. This root contains more than 6 times cucurbitacin of the root of T. kirilowii Maxim. var. japonicum Kitam. PMID:2760813

  14. Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to dietary restriction.

    PubMed

    Fok, Wilson C; Livi, Carolina; Bokov, Alex; Yu, Zhen; Chen, Yidong; Richardson, Arlan; Pérez, Viviana I

    2014-09-01

    Rapamycin, a drug that has been shown to increase lifespan in mice, inhibits the target of rapamycin (TOR) pathway, a major pathway that regulates cell growth and energy status. It has been hypothesized that rapamycin and dietary restriction (DR) extend lifespan through similar mechanisms/pathways. Using microarray analysis, we compared the transcriptome of white adipose tissue from mice fed rapamycin or DR-diet for 6 months. Multidimensional scaling and heatmap analyses showed that rapamycin had essentially no effect on the transcriptome as compared to DR. For example, only six transcripts were significantly altered by rapamycin while mice fed DR showed a significant change in over 1000 transcripts. Using ingenuity pathway analysis, we found that stearate biosynthesis and circadian rhythm signaling were significantly changed by DR. Our findings showing that DR, but not rapamycin, has an effect on the transcriptome of the adipose tissue, suggesting that these two manipulations increase lifespan through different mechanisms/pathways. PMID:25075714

  15. Mononuclear phagocyte accumulates a stearic acid derivative during differentiation into macrophages. Effects of stearic acid on macrophage differentiation and Mycobacterium tuberculosis control.

    PubMed

    Mosquera-Restrepo, Sergio Fabián; Caro, Ana Cecilia; Peláez-Jaramillo, Carlos Alberto; Rojas, Mauricio

    2016-05-01

    The fatty acid composition of monocytes changes substantially during differentiation into macrophages, increasing the proportion of saturated fatty acids. These changes prompted us to investigate whether fatty acid accumulation in the extracellular milieu could affect the differentiation of bystander mononuclear phagocytes. An esterified fatty acid derivative, stearate, was the only fatty acid that significantly increased in macrophage supernatants, and there were higher levels when cells differentiated in the presence of Mycobacterium tuberculosis H37Rv or purified protein derivative (PPD). Exogenous stearic acid enhanced the expression of HLA-DR and CD64; there was also accumulation of IL-12, TNF-α, IL-6, MIP-1 α and β and a reduction in MCP-1 and the bacterial load. These results suggested that during differentiation, a derivative of stearic acid, which promotes the process as well as the effector mechanisms of phagocytes against the mycobacterium, accumulates in the cell supernatants. PMID:26932544

  16. Enzymatic profile of Legionella pneumophilia.

    PubMed

    Müller, H E

    1981-03-01

    The enzyme activities of four strains of Legionella pneumophilia were investigated by using the API ZYM system (API System S.A., F-38390 Montalieu Vercieu, France) and synthetic substrates. Aminopeptidases were detected specifically against L-alanine, L-arginine, L-aspartic acid, L-cystine, L-glutaminic acid, glycine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-tryptophan, L-tyrosine, and L-valine. Furthermore, the bacteria possesses esterase activity splitting propionate, butyrate, caproate, caprylate, and caprate, but not laurate, myristate, palmitate, and stearate, esters. The enzymes studies were inhibited partially by aprotinin. No inhibition of phosphatase (pH range, 5.4 to 8.5) or of phosphoamidase was observed. Activities of arylsulfatase, chymotrypsin, trypsin, and glycosidases could not be detected. PMID:6165735

  17. Testing for ethanol markers in hair: discrepancies after simultaneous quantification of ethyl glucuronide and fatty acid ethyl esters.

    PubMed

    Kintz, P; Nicholson, D

    2014-10-01

    The hair of 97 cases were analysed for ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE, including ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) according to the Society of Hair Testing guidelines to examine the role of both tests in documenting chronic excessive alcohol drinking, particularly when the results are in contradiction. 27 (27.8%) results were EtG negative and FAEE positive, when applying the SoHT cut-offs, probably due to the use of alcohol-containing hair products. Four cases (4.1%) were EtG positive and FAEE negative that were attributed to the use of herbal lotions containing EtG. PMID:24794020

  18. Hydrophobically Modified Keratin Vesicles for GSH-Responsive Intracellular Drug Release.

    PubMed

    Curcio, Manuela; Blanco-Fernandez, Barbara; Diaz-Gomez, Luis; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2015-09-16

    Redox-responsive polymersomes were prepared by self-assembly of a hydrophobically modified keratin and employing a water addition/solvent evaporation method. Polyethylene glycol-40 stearate (PEG40ST) was chosen as hydrophobic block to be coupled to keratin via radical grafting. The amphiphilic polymer exhibited low critical aggregation concentration (CAC; 10 μg/mL), indicating a good thermodynamic stability. The polymeric vesicles loaded both hydrophilic methotrexate and hydrophobic curcumin with high entrapment efficiencies, and showed a GSH-dependent drug release rate. Confocal studies on HeLa cells revealed that the obtained polymersomes were efficiently internalized. Biocompatibility properties of the proposed delivery vehicle were assessed in HET-CAM test and Balb-3T3 mouse fibroblasts. Polymersomes loaded with either methotrexate or curcumin inhibited HeLa and CHO-K1 cancer cells proliferation. Overall, the proposed keratin polymersomes could be efficient nanocarriers for chemotherapeutic agents. PMID:26287808

  19. Preparation of nanoparticulate Fe 2O 3—polymaleic monoester alternating Langmuir—Blodgett films with functional organic hydrophobic part

    NASA Astrophysics Data System (ADS)

    Peng, Xiao-Gang; Gao, Man-Lai; Zhao, Ying-Ying; Kang, Shi-Hai; Zhang, Yun-Hang; Zhang, Yan; Wang, De-Jun; Xiao, Liang-Zhi; Li, Tie-Jin; Chen, Hai-Yan

    1993-07-01

    An organic functional group was introduced into the inorganic nanoparticle—organic alternating LB films by the use of the polymaleic monoester with a functional lateral chain ? to replace a fatty acid. Using the polymer (PMANN), the distance between adjacent nanoparticles in the LB films is apparently decreased and the distribution of the nanoparticles in the monolayer is more homegeneous than that in the nanoparticulate Fe 2O 3—stearate monolayer. All these phenomena are ascribed to the carboxylate groups of a polymer molecule bound to two or more nanoparticles. The photovoltage response of n-type (p-type) silicon coated with a monolayer of nanoparticulate Fe 2O 3—PMANN LB films increases (decreases) for two orders.

  20. Recent Advances in Detailed Chemical Kinetic Models for Large Hydrocarbon and Biodiesel Transportation Fuels

    SciTech Connect

    Westbrook, C K; Pitz, W J; Curran, H J; Herbinet, O; Mehl, M

    2009-03-30

    n-Hexadecane and 2,2,4,4,6,8,8-heptamethylnonane represent the primary reference fuels for diesel that are used to determine cetane number, a measure of the ignition property of diesel fuel. With the development of chemical kinetics models for these two primary reference fuels for diesel, a new capability is now available to model diesel fuel ignition. Also, we have developed chemical kinetic models for a whole series of large n-alkanes and a large iso-alkane to represent these chemical classes in fuel surrogates for conventional and future fuels. Methyl decanoate and methyl stearate are large methyl esters that are closely related to biodiesel fuels, and kinetic models for these molecules have also been developed. These chemical kinetic models are used to predict the effect of the fuel molecule size and structure on ignition characteristics under conditions found in internal combustion engines.

  1. Thermoplasticization of euglenoid β-1,3-glucans by mixed esterification.

    PubMed

    Shibakami, Motonari; Tsubouchi, Gen; Hayashi, Masahiro

    2014-05-25

    We experimentally demonstrated that paramylon, a storage polysaccharide of Euglena gracilis, is efficiently thermoplasticized by adding acyl groups that differ in alkyl chain length. Glass transition temperature of mixed paramylon esters was higher than those of plant-based polylactic acid (PLA), poly 11-aminoundecanoic acid (PA11), and petroleum-based acrylonitrile-butadiene-styrene (ABS) resin and was comparable to that of cellulose acetate stearate (CAS). Their thermoplasticity was equivalent to or higher than those of these reference plastics. The bending strength and bending elastic modulus of injection molded test specimens made from mixed paramylon esters were comparable to those of the reference plastics. While their impact strength was lower than that of specimens made from ABS resin and CAS, it was comparable to those of PLA and PA11. Euglenoid β-1,3-glucans are thus a potential component of thermoplastic materials. PMID:24708957

  2. Fbis report. Science and technology: China, August 18, 1995

    SciTech Connect

    1995-08-18

    ;Contents: Impact of 1996-2010 World`s S&T Progress on China`s Social andEconomic Development; Microstructure of Nanocrystalline Materials; AFM Observation of Surface Nanoscale Lithography on Cadmium Stearate LB FilmStructure; Success in Inserting Anti-Bacteria Peptide Gene Into Rice; Achievements Made in Shandong Academy of Agricultural Sciences; ShanghaiCompletes Satellite/Computer Information Network System; Zhejiag University Holds International Virtual Reality Conference; China Develops First Domestic Automonous Underwater Robot; Reports on Diamond Thin Films; Beijing Telecom Expert Proposes Tactics for Developing `Capital Information Highway`; MPT To Build Jinan-Shijiazhuang- Taiyuan-Yinchuan Fiber Optic Cable; CAS Institute Unveils World-Class Chemical Oxygen-Iodine Laser; Tarium Oil Field Update; Three Largest Natural Gas Fields in Western China; World`s FirstS-Shaped Oil Well Goes Into Operation; China`s Largest Coastal Wind Power Gnerating Field--Nan`ao.

  3. Cytoplasmic tail length influences fatty acid selection for acylation of viral glycoproteins.

    PubMed Central

    Veit, M; Reverey, H; Schmidt, M F

    1996-01-01

    We report remarkable differences in the fatty acid content of thioester-type acylated glycoproteins of enveloped viruses from mammalian cells. The E2 glycoprotein of Semliki Forest virus contains mainly palmitic acid like most other palmitoylated proteins analysed so far. However, the other glycoprotein (E1) of the same virus, as well as the HEF (haemagglutinin esterase fusion) glycoprotein of influenza C virus, are unique in this respect because they are acylated primarily with stearic acid. Comparative radiolabelling of uninfected cells with different fatty acids suggests that stearate may also be the prevailing fatty acid in some cellular acylproteins. To look for further differences between palmitoylated and stearoylated glycoproteins we characterized stearoylation in more detail. We identified the acylation site of HEF as a cysteine residue located at the boundary between the transmembrane region and the cytoplasmic tail. The attachment of stearate to HEF and E1 occurs post-translationally in a pre-Golgi compartment. Thus, stearoylated and palmitoylated proteins cannot be discriminated on the basis of the fatty acid linkage site or the intracellular compartment, where acylation occurs. However, stearoylated acylproteins contain a very short, positively charged cytoplasmic tail, whereas in palmitoylated proteins this molecular region is longer. Replacing the short cytoplasmic tail of stearoylated HEF with the long influenza A virus haemagglutinin (HA) tail in an HEF-HA chimera, and subsequent vaccinia T7 expression in CV-1 cells, yielded proteins with largely palmitic acid bound. The reverse chimera, HA-HEF with a short cytoplasmic tail was not fatty acylated at all during expression, indicating that conformational or topological constraints control fatty acid transfer. PMID:8761467

  4. Elaidate, an 18-Carbon Trans-monoenoic Fatty Acid, but not Physiological Fatty Acids Increases Intracellular Zn2+ in Human Macrophages

    PubMed Central

    Zacherl, Janelle R.; Tourkova, Irina; St Croix, Claudette M.; Robinson, Lisa J.; Peck Palmer, Octavia M.; Mihalik, Stephanie J.; Blair, Harry C.

    2015-01-01

    Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 minute treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 hours. To determine longer term effects of trans fatty acids, we compared whole exome mRNA expression of (trans) elaidate to (cis) oleate, 30 μM, at 44 hours in human macrophages. We found that elaidate changed Zn2+-homeostasis gene mRNAs markedly. This might be important because Zn2+ is a major regulator of macrophage activity. Messenger RNAs of seven Zn2+-binding metallothioneins decreased 2–4 fold; the zinc importer SLC39A10 increased 2-fold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn2+-homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 hours. Further, intracellular Zn2+ was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl)amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 hours, only cells treated with elaidate had increased Zn2+. The durable effect of elaidate on Zn2+ activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism. PMID:25358453

  5. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  6. Compaction properties of isomalt.

    PubMed

    Bolhuis, Gerad K; Engelhart, Jeffrey J P; Eissens, Anko C

    2009-08-01

    Although other polyols have been described extensively as filler-binders in direct compaction of tablets, the polyol isomalt is rather unknown as pharmaceutical excipient, in spite of its description in all the main pharmacopoeias. In this paper the compaction properties of different types of ispomalt were studied. The types used were the standard product sieved isomalt, milled isomalt and two types of agglomerated isomalt with a different ratio between 6-O-alpha-d-glucopyranosyl-d-sorbitol (GPS) and 1-O-alpha-d-glucopyranosyl-d-mannitol dihydrate (GPM). Powder flow properties, specific surface area and densities of the different types were investigated. Compactibility was investigated by compression of the tablets on a compaction simulator, simulating the compression on high-speed tabletting machines. Lubricant sensitivity was measured by compressing unlubricated tablets and tablets lubricated with 1% magnesium stearate on an instrumented hydraulic press. Sieved isomalt had excellent flow properties but the compactibility was found to be poor whereas the lubricant sensitivity was high. Milling resulted in both a strong increase in compactibility as an effect of the higher surface area for bonding and a decrease in lubricant sensitivity as an effect of the higher surface area to be coated with magnesium stearate. However, the flow properties of milled isomalt were too bad for use as filler-binder in direct compaction. Just as could be expected, agglomeration of milled isomalt by fluid bed agglomeration improved flowability. The good compaction properties and the low lubricant sensitivity were maintained. This effect is caused by an early fragmentation of the agglomerated material during the compaction process, producing clean, lubricant-free particles and a high surface for bonding. The different GPS/GPM ratios of the agglomerated isomalt types studied had no significant effect on the compaction properties. PMID:19327398

  7. Self-Assembled Dehydro[24]annulene Monolayers at the Liquid/Solid Interface: Toward On-Surface Synthesis of Tubular π-Conjugated Nanowires.

    PubMed

    Suzuki, Mitsuharu; Guo, Zhaoqi; Tahara, Kazukuni; Kotyk, Juliet F Khosrowabadi; Nguyen, Huan; Gotoda, Jun; Iritani, Kohei; Rubin, Yves; Tobe, Yoshito

    2016-06-01

    We have studied the self-assembly behavior of dehydro[24]annulene (D24A) derivatives 1, 2a-2d, and 3a-3c at the liquid/solid interface using scanning tunneling microscopy (STM). Both the relative placement and the nature of the four D24A substituents strongly influence the self-assembly pattern. Overall, the eight D24A derivatives examined in this study display seven types of 2D packing patterns. The D24A derivatives 1, 2a, and 3a have either two or four stearate groups and adopt face-on configurations of their macrocyclic cores with respect to the highly oriented pyrolytic graphite (HOPG) surface. Their 2D packing pattern is determined by the interchain spacings and number of stearate substituents. The D24A derivatives 2b-2d and 3b-3c bear hydrogen-bonding carbamate groups to further strengthen intermolecular interactions. Face-on patterns were also observed for most of these compounds, while an unstable edge-on self-assembly was observed in the case of 2b at room temperature. Stable edge-on self-assemblies of D24A derivatives were sought for this work as an important stepping stone to achieving the on-surface topochemical polymerization of these carbon-rich macrocycles into tubular π-conjugated nanowires. The overall factors determining the 2D packing patterns of D24As at the liquid/solid interface are discussed on the basis of theoretical simulations, providing useful guidelines for controlling the self-assembly pattern of future D24A macrocycles. PMID:27183003

  8. Multidimensional Mass Spectrometry Coupled with Separation by Polarity or Shape for the Characterization of Sugar-Based Nonionic Surfactants.

    PubMed

    Katzenmeyer, Bryan C; Hague, Shayna F; Wesdemiotis, Chrys

    2016-01-01

    Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were interfaced with ultra-performance liquid chromatography (UPLC) and ion mobility (IM) separation to characterize a complex nonionic surfactant, consisting of a methylated glucose core (glucam) conjugated with poly(ethylene oxide) (PEO(n)) branches that were partially esterified with stearic acid to form ethoxylated glucam (PEO(n)-glucam) stearates. Reverse-phase LC-MS afforded fast separation according to polarity into five major fractions. Accurate mass measurements of the ions in the mass spectra extracted from these fractions enabled conclusive identification of six components in the surfactant, including PEO(n)-glucam mono-, di-, and tristearates as well as free and esterified PEO(n) as byproducts. MS/MS experiments provided corroborating evidence for the fatty acid content in each fraction based on the number of stearic acid losses observed. With IM-MS, the total surfactant ions were separated according to charge and shape into four distinct bands. Extracted mass spectra confirmed the presence of two disaccharide stearates in the surfactant, which were undetectable by LC-MS. PEO(n)-glucam tristearates were, however, not observed upon IM-MS. Hence, LC-MS and IM-MS unveiled complementary compositional insight. With each method, certain components were particularly well separated from other ingredients (by either polarity or shape), to be detected with confidence. Consequently, combined LC-MS and IM-MS offer a superior approach for the characterization of surfactants and other amphiphilic polymers and for the differentiation of similarly composed amphiphilic blends. It is finally noteworthy that NH4(+) charges minimized chemical noise in MS mode and Li(+) charges maximized the fragmentation efficiency in MS/MS mode. PMID:26642239

  9. Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.

    PubMed

    Yaméogo, Josias B G; Gèze, Annabelle; Choisnard, Luc; Putaux, Jean-Luc; Mazet, Roseline; Passirani, Catherine; Keramidas, Michelle; Coll, Jean-Luc; Lautram, Nolwenn; Bejaud, Jérôme; Semdé, Rasmané; Wouessidjewe, Denis

    2014-11-01

    In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by γ-CD-C10 nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded γ-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the conducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART. PMID:25204521

  10. Naturally-occurring estradiol-17{beta}-fatty acid esters, but not estradiol-17{beta}, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

    SciTech Connect

    Mills, Laura H.; Yu Jina; Xu Xiaomeng; Lee, Anthony J.; Zhu Baoting

    2008-06-15

    Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17{beta}-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17{beta} pellet developed large pituitary tumors (average weight = 251 {+-}103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17{beta}-stearate and estradiol-17{beta}-palmitate (two representative estradiol-17{beta}-fatty acid esters) or in the 29 animals implanted with estradiol-17{beta}-stearate alone (in the same molar dose as estradiol-17{beta}), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17{beta} is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17{beta}-fatty acid esters have a higher efficacy than estradiol-17{beta} in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17{beta}-fatty acid esters as preferential inducers of mammary tumorigenesis.

  11. Solidlike and liquidlike behavior in monolayers and multilayers of metal-bearing amphiphiles.

    PubMed

    Mukherjee, Smita; Datta, Alokmay; Giglia, Angelo; Mahne, Nicola; Nannarone, Stefano

    2011-08-01

    Atomic force microscopy (AFM) of cadmium stearate (CdSt) and cobalt stearate (CoSt) Langmuir-Blodgett films show differences in their in-plane morphologies. CdSt films, with a huge number of in-plane "pinhole" defects, follow self-affine behavior, whereas CoSt films, which are almost void of such in-plane defects, show deviation from self-affinity especially at small length scales, suggesting liquidlike behavior, imparting flexibility to the system, in plane. Phase images of CoSt obtained from tapping mode AFM show gentle undulations or hemispherelike features in contrast to its smooth topography, unlike the CdSt system where both height and phase images show self-affine domains. Near edge x-ray absorption fine structure spectroscopy indicates no preferred in-plane orientation of the head group in CoSt films. The undulating features in CoSt is explained by invoking a radially symmetric orientational distribution in the tilt of adjacent hydrocarbon tails, causing a small in-plane density variation which shows up in the phase image. These orientational disorders in adjacent tails probably allow "filling up" of in-plane defects thereby giving rise to its excellent in-plane coverage and hence a "liquidlike" behavior in CoSt. Brewster angle microscopy shows that parent Langmuir monolayers of stearic acid in the presence of Cd and Co ions in the aqueous subphase behave as two-dimensional "solids" and "liquids," respectively, suggesting the phenomena to be inherent in the amphiphiles and probably independent of their organization as monolayers and multilayers. PMID:21928998

  12. Thermal behaviour of procaine and benzocaine Part II: compatibility study with some pharmaceutical excipients used in solid dosage forms

    PubMed Central

    2013-01-01

    Background The compatibility study of active substances with excipients finds an important role in the domain of pharmaceutical research, being known the fact that final formulation is the one administered to the patient. In order to evaluate the compatibility between active substance and excipients, different analytical techniques can be used, based on their accuracy, reproducibility and fastness. Results Compatibility study of two well-known active substances, procaine and benzocaine, with four commonly used excipients, was carried out employing thermal analysis (TG/DTG/HF) and Fourier Transform Infrared Spectroscopy (UATR-FT-IR). The selected excipients were microcrystalline cellulose, lactose monohydrate, magnesium stearate and talc. Equal proportion of active substance and excipients (w/w) was utilized in the interaction study. The absolute value of the difference between the melting point peak of active substances and the one corresponding for the active substances in the analysed mixture, as well the absolute value of the difference between the enthalpy of the pure active ingredient melting peak and that of its melting peak in the different analysed mixtures were chosen as indexes of the drug-excipient interaction degree. All the results obtained through thermal analysis were also sustained by FT-IR spectroscopy. Conclusions The corroboration of data obtained by thermal analysis with the ones from FT-IR spectroscopy indicated that no interaction occurs between procaine and benzocaine, with microcrystalline cellulose and talc, as well for the benzocaine-lactose mixture. Interactions were confirmed between procaine and benzocaine respectively and magnesium stearate, and for procaine and lactose. PMID:23962059

  13. CONSUMING A BALANCED HIGH FAT DIET FOR 16 WEEKS IMPROVES BODY COMPOSITION, INFLAMMATION AND VASCULAR FUNCTION PARAMETERS IN OBESE PREMENOPAUSAL WOMEN

    PubMed Central

    Silver, Heidi J.; Kang, Hakmook; Keil, Charles D.; Muldowney, James A.; Kocalis, Heidi; Fazio, Sergio; Vaughan, Douglas E.; Niswender, Kevin D.

    2014-01-01

    Objective Inflammation, insulin resistance and vascular dysfunction characterize obesity and predict development of cardiovascular disease (CVD). Although women experience CVD events at an older age, vascular dysfunction is evident 10 years prior to coronary artery disease. Questions remain whether replacing SFA entirely with MUFA or PUFA is the optimal approach for cardiometabolic benefits. This study tested the hypotheses that: a) body composition, inflammation and vascular function would improve with a high fat diet (HFD) when type of fat is balanced as 1/3 SFA, 1/3 MUFA and 1/3 PUFA; and b) body composition, inflammation and vascular function would improve more when balanced HFD is supplemented with 18C fatty acids, in proportion to the degree of 18C unsaturation. Methods Obese premenopausal women were stabilized on balanced HFD and randomized to consume 9 g/d of encapsulated stearate (18:0), oleate (18:1), linoleate (18:2) or placebo. Results Significant improvements occurred in fat oxidation rate (↑6%), body composition (%fat: ↓2.5 ± 2.1%; %lean: ↑2.5 ± 2.1%), inflammation (↓ IL-1α, IL-1β, 1L-12, Il-17, IFNγ, TNFα, TNFβ) and vascular function (↓BP, ↓PAI-1, ↑tPA activity). When compared to HFD+placebo, HFD+stearate had the greatest effect on reducing IFNγ (↓74%) and HFD+linoleate had the greatest effect on reducing PAI-1 (↓31%). Conclusions Balancing the type of dietary fat consumed (SFA/MUFA/PUFA) is a feasible strategy to positively affect markers of CVD risk. Moreover, reductions in inflammatory molecules involved in vascular function might be enhanced when intake of certain 18C fatty acids is supplemented. Long term effects need to be determined for this approach. PMID:24559846

  14. Placental Fatty Acid Ethyl Esters Are Elevated with Maternal Alcohol Use in Pregnancies Complicated by Prematurity

    PubMed Central

    Gauthier, Theresa W.; Mohan, Sowmya S.; Gross, Teresa S.; Harris, Frank L.; Guidot, David M.; Brown, Lou Ann S.

    2015-01-01

    The accumulation of fatty acid ethyl esters (FAEEs) in meconium of term newborns has been described as one potential biomarker of maternal alcohol use during pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the placenta. Limited research has focused on the identification of the premature newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use occurs in a significant proportion of premature deliveries and that this exposure can be detected as elevated placental FAEEs. The goals of this study were to 1) determine the prevalence of maternal alcohol use in the premature newborn and 2) investigate whether placental FAEEs could identify those newborns with fetal alcohol exposure. This prospective observational study evaluated 80 placentas from 80 women after premature delivery. Subjects were interviewed for alcohol intake and placental FAEEs were quantified via GC/MS. Receiver Operator Characteristic (ROC) Curves were generated to evaluate the ability of placental FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were generated to adjust for gestational age, maternal smoking, and illicit drug use. 30% of the subjects admitted to drinking alcohol during pregnancy and approximately 14% answered questions indicative of problem drinking (designated AUDIT+). The specific FAEEs ethyl stearate and linoleate, as well as combinations of oleate + linoleate + linolenate (OLL) and of OLL + stearate, were significantly (p<0.05) elevated in placentas from AUDIT+ pregnancies. Adjusted ROC Curves generated areas under the curve ranging from 88–93% with negative predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one third of premature pregnancies were alcohol-exposed, and that elevated placental FAEEs hold great promise to accurately determine maternal alcohol use, particularly heavy use, in pregnancies complicated by premature delivery. PMID:25978403

  15. A simple route to alloyed quaternary nanocrystals Ag-In-Zn-S with shape and size control.

    PubMed

    Gabka, Grzegorz; Bujak, Piotr; Giedyk, Kamila; Ostrowski, Andrzej; Malinowska, Karolina; Herbich, Jerzy; Golec, Barbara; Wielgus, Ireneusz; Pron, Adam

    2014-05-19

    A convenient method of the preparation of alloyed quaternary Ag-In-Zn-S nanocrystals is elaborated, in which a multicomponent mixture of simple and commercially available precursors, namely, silver nitrate, indium(III) chloride, zinc stearate, 1-dodecanethiol, and sulfur, is used with 1-octadecene as a solvent. The formation of quaternary nanocrystals necessitates the use of an auxiliary sulfur precursor, namely, elemental sulfur dissolved in oleylamine, in addition to 1-dodecanethiol. Without this additional precursor binary ZnS nanocrystals are formed. The optimum reaction temperature of 180 °C was also established. In these conditions shape, size, and composition of the resulting nanocrystals can be adjusted in a controlled manner by changing the molar ratio of the precursors in the reaction mixture. For low zinc stearate contents anisotropic rodlike (ca.3 nm x 10 nm) and In-rich nanocrystals are obtained. This is caused by a significantly higher reactivity of the indium precursor as compared to the zinc one. With increasing zinc precursor content the reactivities of both precursors become more balanced, and the resulting nanocrystals are smaller (1.5-4.0 nm) and become Zn-rich as evidenced by transmission electron microscopy, X-ray diffraction, and energy-dispersive spectrometry investigations. Simultaneous increases in the zinc and sulfur precursor content result in an enlargement of nanocrystals (2.5 to 5.0 nm) and further increase in the molar ZnS content (up to 0.76). The prepared nanoparticles show stable photoluminescence with the quantum yield up to 37% for In and Zn-rich nanocrystals. Their hydrodynamic diameter in toluene dispersion, determined by dynamic light scattering, is roughly twice larger than the diameter of their inorganic core. PMID:24786548

  16. Structural- and optical-property characterization of three-dimensional branched ZnO nanospikes

    SciTech Connect

    Chia, M.Y.; Chiu, W.S.; Daud, S.N.H.; Khiew, P.S.; Radiman, S.; Abd-Shukor, R.; Hamid, M.A.A.

    2015-08-15

    Current study reports the synthesis of three-dimensional (3-D) ZnO nanospikes with anomalous optical property, where zinc stearate is adopted as a safe, common and low-cost precursor that undergoes thermal pyrolysis under non-hydrolytic approach. High resolution transmission electron microscope (HRTEM) and scanning electron microscope (SEM) result show that the as-synthesized 3-D ZnO nanospikes are constructed by bundle of nanorods that sprout radially outwards in random orientation. The possible growth mechanism is discussed by referring to the microscopy results. X-ray diffraction (XRD) pattern confirms that the nanospikes are highly crystalline, which existed in hexagonal wurtzite crystal structure. Optical absorption characterization shows that the onset absorption for the nanospikes is slightly red-shifted if compared to commercial ZnO and the corresponding bandgap energy is estimated to be 3.1 eV. The photoluminescene (PL) result of ZnO nanospikes indicate that its optical emission exhibits weak UV emission but very intense visible-light emission that ranged from green- up to red-region. The factors that contributed to the intriguing PL characteristic are discussed. Current finding would offer a versatile synthesis scheme in engineering advanced nanostructures with new design that exhibit congruent optical property. - Graphical abstract: Display Omitted - Highlights: • Pyrolysis of zinc stearate in synthesizing 3-D ZnO nanospikes • ZnO nanospikes possess bundle of nanorods that sprout out from the hexagonal stump • Growth mechanism is deduced to elucidate the morphological evolution from nanobullet to nanospike with branching topology • PL spectrum indicate that the nanospike exhibit prominent visible-light emission that ranged from green- to red-region.

  17. Palmitate-induced changes in energy demand cause reallocation of ATP supply in rat and human skeletal muscle cells.

    PubMed

    Nisr, Raid B; Affourtit, Charles

    2016-09-01

    Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes because skeletal muscle energy metabolism is mostly controlled by ATP demand. Probing the bioenergetics of rat and human myoblasts in real time we show here that the saturated fatty acid palmitate lowers the rate and coupling efficiency of oxidative phosphorylation under conditions it causes insulin resistance. Stearate affects the bioenergetic parameters similarly, whereas oleate and linoleate tend to decrease the rate but not the efficiency of ATP synthesis. Importantly, we reveal that palmitate influences how oxidative ATP supply is used to fuel ATP-consuming processes. Direct measurement of newly made protein demonstrates that palmitate lowers the rate of de novo protein synthesis by more than 30%. The anticipated decrease of energy demand linked to protein synthesis is confirmed by attenuated cycloheximide-sensitivity of mitochondrial respiratory activity used to make ATP. This indirect measure of ATP turnover indicates that palmitate lowers ATP supply reserved for protein synthesis by at least 40%. This decrease is also provoked by stearate, oleate and linoleate, albeit to a lesser extent. Moreover, palmitate lowers ATP supply for sodium pump activity by 60-70% and, in human cells, decreases ATP supply for DNA/RNA synthesis by almost three-quarters. These novel fatty acid effects on energy expenditure inform the 'mitochondrial insufficiency' debate. PMID:27154056

  18. Thermal storage in drywall using organic phase-change material

    SciTech Connect

    Shapiro, M.M.; Feldman, D.; Hawes, D.; Banu, D.

    1987-01-01

    Two mixtures of phase-change material (PCM), 49% butyl stearate with 48% butyl palmitate, and 55% lauric acid with 45% capric acid, diluted 10% with fire retardant, were diffused into 13-mm (0.5-in.) wallboard. No exudation of liquid PCM occurs below 25% by weight. In the wallboard, initial PCM freezing points were 21/sup 0/ and 22/sup 0/C (70/sup 0/ and 72/sup 0/F), respectively, with melting points of 17/sup 0/ and 18/sup 0/C (63/sup 0/ and 64/sup 0/F). For a 4/sup 0/C (7/sup 0/F) temperature swing, thermal storage capacities up to 350 kJ/m/sup 2/ (31 Btu/ft/sup 2/) and 317 kJ/m/sup 2/ (28 Btu/ft/sup 2/), respectively, are available. These are equivalent to about 3.8 cm (1.5 in.) of concrete cycled through 7/sup 0/C (13/sup 0/F). Preliminary tests showed little extra flame spread beyond that of unloaded wallboard. The thermal conductivity of the wallboard increased from 0.19 to 0.22 W/m /sup 0/C (0.11 to 0.13 Btu/h ft /sup 0/F) with liquid PCM. During melting, the effective thermal diffusivity falls from 2.1 x 10/sup -7/ m/sup 2//s (2.3 x 10/sup -6/ ft/sup 2//s) for the unloaded wallboard to 1.4 x 10/sup -7/ m/sup 2//s (1.5 x 10/sup -6/ ft/sup 2//s) with 23.4% butyl stearate-palmitate and to 1.6 x 10/sup -7/ m/sup 2//s (1.7 x 10/sup -6/ ft/sup 2//s) with 28% of the lauric-capric mixture. (The mixture fraction is defined as the ratio of PCM mass to gypsum mass.)

  19. Depletion of arachidonic acid from GH3 cells. Effects on inositol phospholipid turnover and cellular activation.

    PubMed Central

    Dudley, D T; Macfarlane, D E; Spector, A A

    1987-01-01

    We have adapted rat pituitary GH3 cells to grow in delipidated culture medium. In response, esterfied linoleic acid and arachidonic acid become essentially undetectable, whereas eicosa-5,8,11-trienoic acid accumulates and oleic acid increases markedly. These changes occur in all phospholipid classes, but are particularly pronounced in inositol phospholipids, where the usual stearate/arachidonate profile is replaced with oleate/eicosatrienoate (n - 9) and stearate/eicosatrienoate (n - 9). Incubation of arachidonate-depleted cells with 10 microM-arachidonic acid for only 24 h results in extensive remodelling of phospholipid fatty acids, such that close-to-normal compositions and arachidonic acid content are achieved for the inositol phospholipids. In comparison studies with arachidonic acid-depleted or -repleted cells, it was found that the arachidonate content does not affect thyrotropin-releasing-hormone (TRH)-stimulated responses measured at long time points, including [32P]Pi labelling of phosphatidylinositol and phosphatidic acid, stimulation of protein phosphorylation, and basal or TRH-stimulated prolactin release. However, transient events such as stimulated breakdown of inositol phospholipids and an initial rise in diacylglycerol are enhanced by the presence of arachidonate. These results show that arachidonic acid itself is not required for operation of the phosphatidylinositol cycle and is not an obligatory intermediate in TRH-mediated GH3 cell activation. It is possible that any structural or functional role of arachidonic acid in these processes is largely met by replacement with eicosatrienoate (n - 9). However, since arachidonate in inositol phospholipids facilitates their hydrolysis upon stimulation by TRH, arachidonic acid apparently may have a specific role in the recognition of these lipids by phospholipase C. Images Fig. 4. PMID:3120699

  20. Synchronization of Ca(2+)-signals within insulin-secreting pseudoislets: effects of gap-junctional uncouplers.

    PubMed

    Squires, P E; Hauge-Evans, A C; Persaud, S J; Jones, P M

    2000-05-01

    The secretory response of the intact islet is greater than the response of individual beta-cells in isolation, and functional coupling between cells is critical in insulin release. The changes in intracellular Ca(2+)([Ca(2+)](i)) which initiate insulin secretory responses are synchronized between groups of cells within the islet, and gap-junctions are thought to play a central role in coordinating signalling events. We have used the MIN6 insulin-secreting cell line, to examine whether uncoupling gap-junctions alters the synchronicity of nutrient- and non-nutrient-evoked Ca(2+)oscillations, or affects insulin secretion. MIN6 cells express mRNA species that can be amplified using PCR primers for connexin 36. A commonly used gap-junctional inhibitor, heptanol, inhibited glucose- and tolbutamide-induced Ca(2+)-oscillations to basal levels in MIN6 cell clusters at concentrations of 0.5 mM and greater, and it had similar effects in pseudoislets when used at 2.5 mM. Lower heptanol concentrations altered the frequency of Ca(2+)transients without affecting their synchronicity, in both monolayers and pseudoislets. Heptanol also had effects on insulin secretion from MIN6 pseudoislets such that 1 mM enhanced secretion while 2.5 mM was inhibitory. These data suggest that heptanol has multiple effects in pancreatic beta-cells, none of which appears to be related to uncoupling of synchronicity of Ca(2+)signalling between cells. A second gap-junction uncoupler, 18 alpha-glycyrrhetinic acid, also failed to uncouple synchronized Ca(2+)-oscillations, and it had no effect on insulin secretion. These data provide evidence that Ca(2+)signalling events occur simultaneously across the bulk mass of the pseudoislet, and suggest that gap-junctions are not required to coordinate the synchronicity of these events, nor is communication via gap junctions essential for integrated insulin secretory responses. PMID:10859595

  1. A Heterotypic Bystander Effect for Tumor Cell Killing after AAVP-mediated Vascular-targeted Suicide Gene Transfer

    PubMed Central

    Trepel, Martin; Stoneham, Charlotte A.; Eleftherohorinou, Hariklia; Mazarakis, Nicholas D.; Pasqualini, Renata; Arap, Wadih; Hajitou, Amin

    2009-01-01

    Suicide gene transfer is the most commonly used cytotoxic approach in cancer gene therapy; however, a successful suicide gene therapy depends on the generation of efficient targeted systemic gene delivery vectors. We recently reported that selective systemic delivery of suicide genes such as the herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells via a novel targeted AAVP vector leads to suppression of tumor growth. This marked effect has been postulated to result primarily from the death of cancer cells by hypoxia following the targeted disruption of tumor blood vessels. Here we investigated whether an additional mechanism of action is involved. We show that there is a heterotypic bystander effect between endothelial cells expressing the HSVtk suicide gene and tumor cells. Treatment of co-cultures of HSVtk-transduced endothelial cells and non-HSVtk-transduced tumor cells with ganciclovir results in the death of both endothelial and tumor cells. Blocking of this effect by 18α-glycyrrhetinic acid indicates that gap junctions between endothelial and tumor cells are largely responsible for this phenomenon. Moreover, the observed bystander killing is mediated by connexin (Cx)43 and Cx26, which are expressed in both endothelial and tumor cell types. Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into host-derived tumor vascular endothelium. These findings add an alternative non-mutually exclusive and potentially synergistic cytotoxic mechanism to cancer gene therapy based on targeted AAVP, and further support the promising role of non-malignant tumor stromal cells as therapeutic targets. PMID:19671758

  2. Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes.

    PubMed

    Matsumoto, Kaori; Hasegawa, Tetsuya; Koyanagi, Junichi; Takahashi, Tamiko; Akimoto, Masayuki; Sugibayashi, Kenji

    2015-06-01

    The metabolic reduction of nabumetone was examined by inhibition and correlation studies using human liver microsomes and cytosol. This reduction was observed in both fractions, with the V(max) values for reduction activity being approximately fourfold higher, and the V(max)/K(m) values approximately three-fold higher, in the microsomes than in the cytosol. The reduction of nabumetone was inhibited by 18β-glycyrrhetinic acid, an 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitor, in the microsomal fraction. The reduction activity was also inhibited by quercetin and menadione [carbonyl reductase (CBR) inhibitors], and by phenolphthalein and medroxyprogesterone acetate [potent inhibitors of aldo-keto reductase (AKR) 1C1, 1C2 and 1C4] in the cytosol. A good correlation (r² = 0.93) was observed between the reduction of nabumetone and of cortisone, as a marker of 11β-HSD activity, in the microsomal fractions. There was also an excellent relationship between reduction of nabumetone and of the AKR1C substrates, acetohexamide, and ethacrynic acid (r 2 = 0.92 and 0.93, respectively), in the cytosol fractions. However, a poor correlation was observed between the formation of 4-(6-methoxy-2-naphthyl)-butan-2-ol (MNBO) from nabumetone and CBR activity (with 4-benzoyl pyridine reduction as a CBR substrate) in the cytosol fractions (r² = 0.24). These findings indicate that nabumetone may be metabolized by 11β-HSD in human liver microsomes, and primarily by AKR1C4 in human liver cytosol, although multiple enzymes in the AKR1C subfamily may be involved. It cannot be completely denied that CBR is involved to some extent in the formation of MNBO from nabumetone in the cytosol fraction. PMID:24659525

  3. Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor

    PubMed Central

    Chauhan, Sharmila D.; Nilsson, Holger; Ahluwalia, Amrita; Hobbs, Adrian J.

    2003-01-01

    Endothelial cells in most vascular beds release a factor that hyperpolarizes the underlying smooth muscle, produces vasodilatation, and plays a fundamental role in the regulation of local blood flow and systemic blood pressure. The identity of this endothelium-derived hyperpolarizing factor (EDHF), which is neither NO nor prostacyclin, remains obscure. Herein, we demonstrate that in mesenteric resistance arteries, release of C-type natriuretic peptide (CNP) accounts for the biological activity of EDHF. Both produce identical smooth muscle hyperpolarizations that are attenuated in the presence of high [K+], the Gi G protein (Gi) inhibitor pertussis toxin, the G protein-gated inwardly rectifying K+ channel inhibitor tertiapin, and a combination of Ba2+ (inwardly rectifying K+ channel blocker) plus ouabain (Na+/K+-ATPase inhibitor). Responses to EDHF and CNP are unaffected by the natriuretic peptide receptor (NPR)-A/B antagonist HS-142-1, but mimicked by the selective NPR-C agonist, cANF4–23. EDHF-dependent relaxation is concomitant with liberation of endothelial CNP; in the presence of the myoendothelial gap-junction inhibitor 18α-glycyrrhetinic acid or after endothelial denudation, CNP release and EDHF responses are profoundly suppressed. These data demonstrate that acetylcholine-evoked release of endothelial CNP activates NPR-C on vascular smooth muscle that via a Gi coupling promotes Ba2+/ouabain-sensitive hyperpolarization. Thus, we have revealed the identity of EDHF and established a pivotal role for endothelial-derived CNP in the regulation of vascular tone and blood flow. PMID:12552127

  4. Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

    PubMed Central

    Lv, Qing-Bo; Gao, Xiang; Lin, Ding-Sheng; Chen, Yun; Cao, Bin; Zhou, Kai-Liang

    2016-01-01

    Partial necrosis of skin flaps continues to restrict the survival of local skin flaps following plastic and reconstructive surgeries. The aim of the present study was to investigate the effects of diammonium glycyrrhizinate (DG), a salt of glycyrrhetinic acid that has been widely used in the therapy of chronic hepatitis and human immunodeficiency virus infection, on random skin flap survival in rats. McFarlane flaps were established in 60 male Sprague-Dawley rats randomly divided into three groups. Group I served as the control group and was injected with saline (10 mg/kg) once per day. Group II and group III were the experimental groups, and were injected with 10 mg/kg DG once and twice per day, respectively. On day 7, the survival area of the flap was measured. Tissue samples were stained with hematoxylin and eosin and immunohistochemically evaluated. Tissue edema, neutrophil density, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were evaluated. The mean survival areas of the flaps of group II were significantly larger when compared with those of group I (P<0.05), and the rats of group III exhibited significantly higher survival areas than group II (P<0.05). Histologic and immunohistochemical evaluation showed that microvessel development and the expression level of vascular endothelial growth factor were higher in the two experimental groups than in the control group. Furthermore, SOD activity was significantly increased (P<0.05), while the neutrophil density and MDA level were significantly reduced (P<0.05) in group II when compared with group I. Significant differences between group II and group III with regard to SOD activity and MDA level were also observed (P<0.05). Thus, DG may have a dose-dependent effect on promoting the survival of random skin flaps. PMID:27588181

  5. Role for electrical synapses in shaping the output of coupled peptidergic neurons from Lymnaea.

    PubMed

    Beekharry, Christopher C; Zhu, Guan Z; Magoski, Neil S

    2015-04-01

    Electrically coupled neurons communicate through channel assemblies called gap junctions, which mediate the transfer of current from one cell to another. Electrical synapses ensure spike synchronization and reliable transmission, which influences bursting patterns and firing frequency. The present study concerns an electrically coupled two-neuron network in the gastropod mollusc, Lymnaea stagnalis. The neurons, designated Visceral Dorsal 1 (VD1) and Right Parietal Dorsal 2 (RPD2), are peptidergic, innervate aspects of the cardio-respiratory system, and show strong coupling, such that they fire synchronously. Using dual sharp-electrode current-clamp recording and morphological staining in isolated brain preparations, the hypothesis that the electrical synapse is necessary for accurate network output was tested. We found that both cells make extensive projections within and out of the brain, including across the visceral-parietal connective, which links VD1 and RPD2. Cutting this connective uncoupled the neurons and disrupted the firing rate and pattern of RPD2 more than VD1, consistent with VD1 being the master and RPD2 the follower. The electrical synapse was inhibited by select gap junction blockers, with niflumic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid decreasing the VD1→RPD2 and RPD2→VD1 coupling coefficients, whereas carbenoxolone, α-glycyrrhetinic acid, meclofenamic acid, and quinine were ineffective. There was little-to-no impact on VD1↔RPD2 firing synchrony or frequency when coupling was reduced pharmacologically. However, in the presence of gap junction blockers, suppressing the activity of VD1 by prolonged hyperpolarization revealed a distinct, low-frequency firing pattern in RPD2. This suggests that strong electrical coupling is key to maintaining a synchronous output and proper firing rate. PMID:25641041

  6. An overview on antidiabetic medicinal plants having insulin mimetic property.

    PubMed

    Patel, D K; Prasad, S K; Kumar, R; Hemalatha, S

    2012-04-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

  7. Pharmacological blockade of gap junctions induces repetitive surging of extracellular potassium within the locust CNS.

    PubMed

    Spong, Kristin E; Robertson, R Meldrum

    2013-10-01

    The maintenance of cellular ion homeostasis is crucial for optimal neural function and thus it is of great importance to understand its regulation. Glial cells are extensively coupled by gap junctions forming a network that is suggested to serve as a spatial buffer for potassium (K(+)) ions. We have investigated the role of glial spatial buffering in the regulation of extracellular K(+) concentration ([K(+)]o) within the locust metathoracic ganglion by pharmacologically inhibiting gap junctions. Using K(+)-sensitive microelectrodes, we measured [K(+)]o near the ventilatory neuropile while simultaneously recording the ventilatory rhythm as a model of neural circuit function. We found that blockade of gap junctions with either carbenoxolone (CBX), 18β-glycyrrhetinic acid (18β-GA) or meclofenamic acid (MFA) reliably induced repetitive [K(+)]o surges and caused a progressive impairment in the ability to maintain baseline [K(+)]o levels throughout the treatment period. We also show that a low dose of CBX that did not induce surging activity increased the vulnerability of locust neural tissue to spreading depression (SD) induced by Na(+)/K(+)-ATPase inhibition with ouabain. CBX pre-treatment increased the number of SD events induced by ouabain and hindered the recovery of [K(+)]o back to baseline levels between events. Our results suggest that glial spatial buffering through gap junctions plays an essential role in the regulation of [K(+)]o under normal conditions and also contributes to a component of [K(+)]o clearance following physiologically elevated levels of [K(+)]o. PMID:23916994

  8. Aspergillus niger Enhance Bioactive Compounds Biosynthesis As Well As Expression of Functional Genes in Adventitious Roots of Glycyrrhiza uralensis Fisch.

    PubMed

    Li, Jing; Wang, Juan; Li, Jinxin; Liu, Dahui; Li, Hongfa; Gao, Wenyuan; Li, Jianli; Liu, Shujie

    2016-02-01

    In the present study, the culture conditions for the accumulation of Glycyrrhiza uralensis adventitious root metabolites in balloon-type bubble bioreactors (BTBBs) have been optimized. The results of the culture showed that the best culture conditions were a cone angle of 90° bioreactor and 0.4-0.6-0.4-vvm aeration volume. Aspergillus niger can be used as a fungal elicitor to enhance the production of defense compounds in plants. With the addition of a fungal elicitor (derived from Aspergillus niger), the maximum accumulation of total flavonoids (16.12 mg g(-1)) and glycyrrhetinic acid (0.18 mg g(-1)) occurred at a dose of 400 mg L(-1) of Aspergillus niger resulting in a 3.47-fold and 1.8-fold increase over control roots. However, the highest concentration of polysaccharide (106.06 mg g(-1)) was achieved with a mixture of elicitors (Aspergillus niger and salicylic acid) added to the medium, resulting in a 1.09-fold increase over Aspergillus niger treatment alone. Electrospray ionization tandem mass spectrometry (ESI-MS(n)) analysis was performed, showing that seven compounds were present after treatment with the elicitors, including uralsaponin B, licorice saponin B2, liquiritin, and (3R)-vestitol, only identified in the mixed elicitor treatment group. It has also been found that elicitors (Aspergillus niger and salicylic acid) significantly upregulated the expression of the cinnamate 4-hydroxylase (C4H), β-amyrin synthase (β-AS), squalene epoxidase (SE) and a cytochrome P450 monooxygenase (CYP72A154) genes, which are involved in the biosynthesis of bioactive compounds, and increased superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activity. PMID:26490378

  9. Role of connexin channels in the retinal light response of a diurnal rodent

    PubMed Central

    Palacios-Muñoz, Angelina; Escobar, Maria J.; Vielma, Alex; Araya, Joaquín; Astudillo, Aland; Valdivia, Gonzalo; García, Isaac E.; Hurtado, José; Schmachtenberg, Oliver; Martínez, Agustín D.; Palacios, Adrian G.

    2014-01-01

    Several studies have shown that connexin channels play an important role in retinal neural coding in nocturnal rodents. However, the contribution of these channels to signal processing in the retina of diurnal rodents remains unclear. To gain insight into this problem, we studied connexin expression and the contribution of connexin channels to the retinal light response in the diurnal rodent Octodon degus (degu) compared to rat, using in vivo ERG recording under scotopic and photopic light adaptation. Analysis of the degu genome showed that the common retinal connexins present a high degree of homology to orthologs expressed in other mammals, and expression of Cx36 and Cx43 was confirmed in degu retina. Cx36 localized mainly to the outer and inner plexiform layers (IPLs), while Cx43 was expressed mostly in cells of the retinal pigment epithelium. Under scotopic conditions, the b-wave response amplitude was strongly reduced by 18-β-glycyrrhetinic acid (β-GA) (−45.1% in degu, compared to −52.2% in rat), suggesting that connexins are modulating this response. Remarkably, under photopic adaptation, β-GA increased the ERG b-wave amplitude in degu (+107.2%) while reducing it in rat (−62.3%). Moreover, β-GA diminished the spontaneous action potential firing rate in ganglion cells (GCs) and increased the response latency of ON and OFF GCs. Our results support the notion that connexins exert a fine-tuning control of the retinal light response and have an important role in retinal neural coding. PMID:25202238

  10. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  11. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  12. Blockade of Gap Junction Hemichannel Suppresses Disease Progression in Mouse Models of Amyotrophic Lateral Sclerosis and Alzheimer's Disease

    PubMed Central

    Takeuchi, Hideyuki; Mizoguchi, Hiroyuki; Doi, Yukiko; Jin, Shijie; Noda, Mariko; Liang, Jianfeng; Li, Hua; Zhou, Yan; Mori, Rarami; Yasuoka, Satoko; Li, Endong; Parajuli, Bijay; Kawanokuchi, Jun; Sonobe, Yoshifumi; Sato, Jun; Yamanaka, Koji; Sobue, Gen; Mizuno, Tetsuya; Suzumura, Akio

    2011-01-01

    Background Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. Methods and Findings In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. Conclusions Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various

  13. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes.

    PubMed

    Ku, Chi-Mei; Lin, Jin-Yuarn

    2013-11-15

    This study investigated 27 selected terpenoid compounds, including 8 monoterpenoids, 7 sesqui-terpenoids, 3 di-terpenoids, 8 tri-terpenoids, and 1 tetra-terpenoid, for their Th1/Th2 immunomodulatory potential using mouse primary splenocytes. Changes in Th1 cytokines, including interleukin (IL)-2 and interferon (IFN)-γ, and Th2 cytokines, including IL-4, IL-5 and IL-10, secreted by terpenoid-treated splenocytes were measured using the ELISA method. The results showed that triptolide, a diterpenoid, was most cytotoxic, reflecting an IC50 value of 46nM. Eucalyptol, limonene, linalool, thymol, parthenolide, andrographolide, 18β-glycyrrhetinic acid, lupeol, ursolic acid and β-sitosterol showed a strong Th2-inclination and anti-inflammation potential in vitro. In addition, (-)-trans-caryophyllene, oridonin, triptolide, diosgenin, betulinic acid, escin, and β-sitosterol treatments significantly inhibited both IL-2 (Th1) and IL-10 (Th2) cytokine production at the same time, suggesting that these terpenoid compounds have an anti-inflammation potential through the inhibition of T-cell immune responses. Diosgenin treatments significantly increased IFN-γ secretion levels using mouse splenocytes, suggesting that diosgenin may be useful in treating a viral infection through the stimulation of IFN-γ production. Menthone, farnesol and oridonin treatments did not markedly increase IL-10/IL-2 (Th2/Th1) cytokine secretion ratios, suggesting that menthone, farnesol and oridonin may have a relative Th1-inclination property, compared to the other selected terpenoid compounds. The relative Th1-inclination property of menthone, farnesol and oridonin may be applied to improve Th2-skewed allergic diseases. PMID:23790892

  14. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

    PubMed Central

    Han, Tao; Hu, Di; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Zhu, Jiaqiao; Liu, Zong-ping

    2015-01-01

    It is known that cadmium (Cd) induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A) and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI) of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC) and activation of mitogen-activated protein kinase (MAPK) pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA), administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK) inhibitor (U0126) and a p38 inhibitor (SB202190) but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways. PMID:26070151

  15. Connexin43 Hemichannels Mediate Small Molecule Exchange between Chondrocytes and Matrix in Biomechanically-Stimulated Temporomandibular Joint Cartilage

    PubMed Central

    Zhang, Jing; Zhang, Hongyun; Zhang, Mian; Qiu, Zhongying; Wu, Yaoping; Callaway, Danielle A.; Jiang, Jean X.; Lu, Lei; Jing, Lei; Yang, Ting; Wang, Meiqing

    2015-01-01

    Objective Connexin (Cx) 43 hemichannels play a role in mechanotransduction. This study was undertaken in order to determine if Cx43 hemichannels were activated in rat temporomandibular joint (TMJ) chondrocytes under mechanical stimulation. Methods Sprague-Dawley rats were stimulated dental-mechanically. Cx43 expression in rat TMJ cartilage was determined with immunohistochemistry and real-time PCR, and Cx43 hemichannel opening was evaluated by the extra- and intracellular levels of prostaglandin E2 (PGE2). Both primary rat chondrocytes and ATDC5 cells were treated with fluid flow shear stress (FFSS) to induce hemichannel opening. The Cx43 expression level was then determined by real-time PCR or western blotting, and the extent of Cx43 hemichannel opening was evaluated by measuring both PGE2 release and cellular dye uptake. Results Cx43 expression and intra- and extracellular PGE2 levels were increased in mechanically-stimulated rat TMJ cartilage compared to the unstimulated control. The FFSS treatment increased Cx43 expression and induced Cx43 hemichannel opening in primary rat chondrocytes and ATDC5 cells indicated by enhanced PGE2 release and dye uptake. Furthermore, the Cx43 hemichannel opening could be blocked by the addition of 18β-glycyrrhetinic acid, a connexin channel inhibitor, Cx43-targeting siRNA, or by withdrawal of FFSS stimulation. The migration of cytosolic Cx43 protein to the plasma membrane in ATDC5 cells was still significant after 8h post 2-h FFSS treatment, and the Cx43 protein level was still high at 48h which returned to control levels at 72h after treatment. Conclusion Cx43 hemichannels are activated and mediate small molecule exchange between TMJ chondrocytes and matrix under mechanical stimulation. PMID:24704497

  16. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    PubMed Central

    Barrett, John M.; Degenaar, Patrick; Sernagor, Evelyne

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-β-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses

  17. Mutual enhancement of differentiation of osteoblasts and osteocytes occurs through direct cell-cell contact

    PubMed Central

    Fujita, Koji; Xing, Qian; Khosla, Sundeep; Monroe, David G.

    2014-01-01

    There is increasing evidence that osteocytes regulate multiple aspects of bone remodeling through bi-directional communication with osteoblasts. This is potentially mediated through cell-cell contact via osteocytic dendritic processes, through the activity of secreted factors, or both. To test whether cell-cell contact affects gene expression patterns in osteoblasts and osteocytes, we used a co-culture system where calvarial osteoblasts and IDG-SW3 osteocytes were allowed to touch through a porous membrane, while still being physically separated to allow for phenotypic characterization. Osteoblast/osteocyte cell-contact resulted in up-regulation of osteoblast differentiation genes in the osteoblasts, when compared to wells where no cell contact was allowed. Examination of osteocyte gene expression when in direct contact with osteoblasts also revealed increased expression of osteocyte-specific genes. These data suggest that physical contact mutually enhances both the osteoblastic and osteocytic character of each respective cell type. Interestingly, Gja1 (a gap junction protein) was increased in the osteoblasts only when in direct contact with the osteocytes, suggesting that Gja1 may mediate some of the effects of direct cell contact. To test this hypothesis, we treated the direct contact system with the gap junction inhibitor 18-alpha-glycyrrhetinic acid and found that Bglap expression was significantly inhibited. This suggests that osteocytes may regulate late osteoblast differentiation at least in part through Gja1. Identification of the specific factors involved in the enhancement of differentiation of both osteoblasts and osteocytes when in direct contact will uncover new biology concerning how these bone cells communicate. PMID:25043105

  18. Intercellular Communication Amplifies Stressful Effects in High-Charge, High-Energy (HZE) Particle-Irradiated Human Cells

    PubMed Central

    AUTSAVAPROMPORN, Narongchai; DE TOLEDO, Sonia M.; BUONANNO, Manuela; JAY-GERIN, Jean-Paul; HARRIS, Andrew L.; AZZAM, Edouard I.

    2014-01-01

    Understanding the mechanisms that underlay the biological effects of particulate radiations is essential for space exploration and for radiotherapy. Here, we investigated the role of gap junction intercellular communication (GJIC) in modulating harmful effects induced in confluent cultures wherein most cells are traversed by one or more radiation tracks. We focused on the effect of radiation quality (linear energy transfer; LET) on junctional propagation of DNA damage and cell death among the irradiated cells. Confluent normal human fibroblasts were exposed to graded doses of 1 GeV protons (LET ~0.2 keV/μm) or 1 GeV/u iron ions (LET ~151 keV/μm) and were assayed for clonogenic survival and for micronucleus formation, a reflection of DNA damage, shortly after irradiation and following longer incubation periods. Iron ions were ~2.7 fold more effective than protons at killing 90% of the cells in the exposed cultures when assayed within 5–10 minutes after irradiation. When cells were held in the confluent state for several hours after irradiation, substantial repair of potentially lethal damage (PLDR), coupled with a reduction in micronucleus formation, occurred in cells exposed to protons, but not in those exposed to iron ions. In fact, such confluent holding after exposure to a similarly toxic dose of iron ions enhanced the induced toxic effect. However, following iron ion irradiation, inhibition of GJIC by 18-α-glycyrrhetinic acid eliminated the enhanced toxicity and reduced micronucleus formation to levels below those detected in cells assayed shortly after irradiation. The data show that low LET radiation induces strong PLDR within hours, but that high LET radiation with similar immediate toxicity does not induce PLDR and its toxicity increases with time following irradiation. The results also show that GJIC among irradiated cells amplifies stressful effects following exposure to high, but not LET radiation, and that GJIC has only minimal effect on cellular

  19. Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal.

    PubMed

    Yu, Jie; Berga, Sarah L; Johnston-MacAnanny, Erika B; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

    2016-06-01

    Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity. PMID:27035651

  20. An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

    PubMed Central

    2012-01-01

    Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. Methods 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Results Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. Conclusions These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection. PMID:22834653

  1. Role of gap junctions and protein kinase A during the development of oocyte maturational competence in Ayu (Plecoglossus altivelis)

    USGS Publications Warehouse

    Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Patino, R.

    2008-01-01

    Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18??-glycyrrhetinic acid (??-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20??-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption. ?? 2007 Elsevier Inc. All rights reserved.

  2. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    PubMed

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. PMID:23954169

  3. An overview on antidiabetic medicinal plants having insulin mimetic property

    PubMed Central

    Patel, DK; Prasad, SK; Kumar, R; Hemalatha, S

    2012-01-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

  4. Effect of the liquorice root derivatives on salt and water balance in a teleost fish, rainbow trout (Oncorhynchus mykiss).

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2015-02-01

    The effect of liquorice root derivatives (LRDs) glycyrrhizic acid (GL) and glycyrrhetinic acid (18βGA) on salt and water balance and end points of gill ion transport in a freshwater teleost, (rainbow trout) was examined after feeding fish diets containing GL or 18βGA (0, 5, 50 or 500 µg/g diet) for a two week period. Serum cortisol levels and gill 11β-hydroxysteroid dehydrogenase type 2 mRNA abundance decreased in fish fed GL but increased (at select doses) in fish fed 18βGA. At higher doses of GL, gill Na(+)-K(+)-ATPase and H(+)-ATPase activity increased, while cystic fibrosis transmembrane conductance regulator type II mRNA abundance significantly decreased at the lowest dose of GL. End points of gill transcellular ion transport were not significantly altered in fish fed 18βGA, except for a reduction in Na(+)-K(+)-ATPase activity at a 50 µg/g dose. In contrast, high doses of GL and 18βGA increased gill transcript abundance of the tight junction protein claudin-31 (cldn-31). Other end points of gill paracellular transport differed in fishes fed LRDs. Tricellulin mRNA abundance was increased by high dose GL and decreased by high dose 18βGA, and cldn-23a and cldn-27b mRNA abundance significantly decreased in response to GL irrespective of dose. Despite the above observations, systemic end points of salt and water balance (i.e. serum [Na(+)] and [Cl(-)] as well as muscle moisture) were unaffected by LRDs. Therefore data suggest that LRDs can alter end points of ion transport in fishes but that overall salt and water balance need not be perturbed. PMID:25460830

  5. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice.

    PubMed

    Barrett, John M; Degenaar, Patrick; Sernagor, Evelyne

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-β-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses

  6. Effect of licorice on the reduction of body fat mass in healthy subjects.

    PubMed

    Armanini, D; De Palo, C B; Mattarello, M J; Spinella, P; Zaccaria, M; Ermolao, A; Palermo, M; Fiore, C; Sartorato, P; Francini-Pesenti, F; Karbowiak, I

    2003-07-01

    The history of licorice, as a medicinal plant, is very old and has been used in many societies throughout the millennia. The active principle, glycyrrhetinic acid, is responsible for sodium retention and hypertension, which is the most common side-effect. We show an effect of licorice in reducing body fat mass. We studied 15 normal-weight subjects (7 males, age 22-26 yr, and 8 females, age 21-26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of licorice. Body fat mass (BFM, expressed as percentage of total body weight, by skinfold thickness and by bioelectrical impedance analysis, BIA) and extracellular water (ECW, percentage of total body water, by BIA) were measured. Body mass index (BMI) did not change. ECW increased (males: 41.8+/-2.0 before vs 47.0+/-2.3 after, p<0.001; females: 48.2+/-1.4 before vs 49.4+/-2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0+/-2.1 vs after 10.8+/-2.9%, p<0.02; female: before 24.9+/-5.1 vs after 22.1+/-5.4, p<0.02); plasma renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce body fat mass and to suppress aldosterone, without any change in BMI. Since the subjects were consuming the same amount of calories during the study, we suggest that licorice can reduce fat by inhibiting 11beta-hydroxysteroid dehydrogenase Type 1 at the level of fat cells. PMID:14594116

  7. Laminin-111 stimulates proliferation of mouse embryonic stem cells through a reduction of gap junctional intercellular communication via RhoA-mediated Cx43 phosphorylation and dissociation of Cx43/ZO-1/drebrin complex.

    PubMed

    Suh, Han Na; Kim, Mi Ok; Han, Ho Jae

    2012-07-20

    Gap junctions within extracellular matrix (ECM)-defined boundaries ensure synchronous activity between cells destined to become functional mediators that regulate cell behavior. However, the role of ECM in connexin (Cx) function in mouse embryonic stem cells (mESCs) has not been elucidated. Therefore, we examined the role of laminin-111 in the control of Cx43 functions and related signal pathways in mESCs. ECM components (laminin-111, fibronectin, and collagen I) increased Cx43 phosphorylation and decreased Lucifer yellow (Ly) diffusion. In addition, laminin-111 increased the proliferation index through reduction of gap junctional intercellular communication (GJIC), which was confirmed by 18α-glycyrrhetinic acid (18α-GA). Laminin-111 increased phosphorylation of focal adhesion kinase (FAK)/Src and protein kinase C (PKC), which were inhibited by integrin β1 antibody (Ab) and laminin receptor-1 (LR-1) Ab, respectively. In addition, inhibition of both FAK/Src and PKC blocked Cx43 phosphorylation. Laminin-111 increased the Ras homolog gene family, member A (RhoA) activation, which was blocked by FAK/Src and PKC inhibitors, suggesting the existence of parallel pathways that merge at RhoA. Inhibition of RhoA reversed the laminin-111-induced increase of Cx43 phosphorylation and reduction of GJIC. Laminin-111 also stimulated the dissociation of Cx43/ZO-1 complex followed by disruption of Cx43/drebrin and Cx43/F-actin complexes, which were reversed by C3 (RhoA inhibitor). ZO-1 small interfering (si) RNA significantly decreased Ly diffusion. Moreover, laminin-111 decreased Cx43 labeling at the intercellular junction, whereas pretreatment with degradation inhibitors (lysosomal protease inhibitor, chloroquine; proteasome inhibitor, lactacystin) increased Cx43 expression, reversely. In conclusion, laminin-111 stimulated mESC proliferation through a reduction of GJIC via RhoA-mediated Cx43 phosphorylation and Cx43/ZO-1/drebrin complex instability-mediated Cx43 degradation

  8. Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

    PubMed

    Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

    2016-01-01

    Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. PMID:26565022

  9. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    PubMed

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  10. Temporal sequence of activation of cells involved in purinergic neurotransmission in the colon

    PubMed Central

    Baker, Salah A; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

    2015-01-01

    Interstitial cells, known as platelet derived growth factor receptor α (PDGFRα+) cells, are closely associated with varicosities of enteric motor neurons and suggested to mediate purinergic hyperpolarization responses in smooth muscles of the gastrointestinal tract (GI), but this concept has not been demonstrated directly in intact muscles. We used confocal microscopy to monitor Ca2+ transients in neurons and post-junctional cells of the murine colon evoked by exogenous purines or electrical field stimulation (EFS) of enteric neurons. EFS (1–20 Hz) caused Ca2+ transients in enteric motor nerve processes and then in PDGFRα+ cells shortly after the onset of stimulation (latency from EFS was 280 ms at 10 Hz). Responses in smooth muscle cells (SMCs) were typically a small decrease in Ca2+ fluorescence just after the initiation of Ca2+ transients in PDGFRα+ cells. Upon cessation of EFS, several fast Ca2+ transients were noted in SMCs (rebound excitation). Strong correlation was noted in the temporal characteristics of Ca2+ transients evoked in PDGFRα+ cells by EFS and inhibitory junction potentials (IJPs) recorded with intracellular microelectrodes. Ca2+ transients and IJPs elicited by EFS were blocked by MRS-2500, a P2Y1 antagonist, and absent in P2ry1(−/−) mice. PDGFRα+ cells expressed gap junction genes, and gap junction uncouplers, 18β-glycyrrhetinic acid (18β-GA) and octanol blocked Ca2+ transients in SMCs but not in neurons or PDGFRα+ cells. IJPs recorded from SMCs were also blocked. These findings demonstrate direct innervation of PDGFRα+ cells by motor neurons. PDGFRα+ cells are primary targets for purinergic neurotransmitter(s) in enteric inhibitory neurotransmission. Hyperpolarization responses are conducted to SMCs via gap junctions. PMID:25627983

  11. Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of α₂A-adrenoceptor.

    PubMed

    Nakagawa, T; Nagayasu, K; Nishitani, N; Shirakawa, H; Sekiguchi, K; Ikarashi, Y; Kase, Y; Kaneko, S

    2012-12-27

    Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18β-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade. PMID:23069764

  12. Thermal Decomposition of Methyl Esters in Biodiesel Fuel: Kinetics, Mechanisms and Products

    NASA Astrophysics Data System (ADS)

    Chai, Ming

    Biodiesel continues to enjoy increasing popularity. However, recent studies on carbonyl compounds emissions from biodiesel fuel are inconclusive. Emissions of carbonyl compounds from petroleum diesel fuels were compared to emissions from pure biodiesel fuels and petroleum-biodiesel blends used in a non-road diesel generator. The concentration of total carbonyl compounds was the highest when the engine was idling. The carbonyl emissions, as well as ozone formation potential, from biodiesel fuel blends were higher than those emitted from petroleum diesel fuel. The sulfur content of diesel fuel and the source of biodiesel fuel were not found to have a significant impact on emissions of carbonyl compounds. Mechanism parameters of the thermal decomposition of biodiesel-range methyl esters were obtained from the results of thermal gravimetric analysis (TGA). The overall reaction orders are between 0.49 and 0.71 and the energies of activation are between 59.9 and 101.3 kJ/mole. Methyl esters in air have lower activation energies than those in nitrogen. Methyl linoleate has the lowest activation energy, followed by methyl oleate, and methyl stearate. The pyrolysis and oxidation of the three methyl esters were investigated using a semi-isothermal tubular flow reactor. The profiles of major products versus reaction temperature are presented. In the pyrolysis of methyl stearate, the primary reaction pathway is the decarboxylic reaction at the methyl ester functional group. Methyl oleate's products indicate more reactions on its carbon-carbon double bond. Methyl linoleate shows highest reactivity among the three methyl esters, and 87 products were detected. The oxidation of three methyl esters resulted in more products in all compound classes, and 55, 114, and 127 products were detected, respectively. The oxidation of methyl esters includes decarboxylation on ester group. The methyl ester's carbon chain could be oxidized as a hydrocarbon compound and form oxidized esters and

  13. Examination of particle/particle interactions and their impact on rheology and mixedness of an alumina/titania system

    NASA Astrophysics Data System (ADS)

    August, Cari R.

    In the manufacturing of ceramic particulate composites, improved manufacturing efficiency means two things, ease of production and increased performance. The effect of mixedness on the rheology of alumina-titania blends has been evaluated. Alumina and titania starting powders that have been examined ranged in particle size from nanoscale (50-200 nm) to micron scale (1-5 microm). Nano and micro-alumina powders have been combined individually with macro and micro-titania powders to determine how the nano/micro structure affects rheological properties and the mixedness of the final blended compositions. The effects of varying the mixing and processing techniques used to create the compositions; such as ball milling, wet mixing, high shear mixing, and varied mixing time, has been analyzed. The effect of varying surfactant additions (sodium stearate) on the mixedness and rheology of the alumina-titania blends has also been evaluated. The range of surfactant concentrations covers the measured adsorption limits of the particles in the blend, allowing sodium stearate to act not only as surfactant, but also as bulk lubricant. Rheological evaluation of these blends included torque, dynamic stress, and capillary rheometry. Dynamic stress rheometry measures and compares the viscous modulus and the shear modulus of a blend, allowing determination of its dynamic yield stress. Capillary rheometry was used to evaluate the extrusion pressures of the alumina-titania batches, for analysis with a Benbow-Bridgewater model, yielding information on extrusion wall stresses and extrudate bulk strength. The mixedness was evaluated by SEM-EDS method, which created a compositional map of a cross-sectional area of extrudate for distributional evaluation by nearest neighbor and standard deviation calculations. It was found that the use of nano-alumina and macro-titania increased processing requirements such as mixing energy and extrusion pressure, but produced extrudates with minimal flaws

  14. Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy.

    PubMed

    Qu, Ding; Sun, Wenjie; Liu, Mingjian; Liu, Yuping; Zhou, Jing; Chen, Yan

    2016-04-30

    A hepatic tumor bitargeted microemulsions drug delivery system using coix seed oil and coix seed polysaccharide (CP) acting as anticancer components, as well as functional excipients, was developed for enhanced tumor-specific accumulation by CP-mediated enhancement on passive tumor targeting and modification of galactose stearate (tumor-targeted ligand). In the physicochemical characteristics studies, galactose stearate-modified coix seed multicomponent microemulsions containing 30% CP (w%) (Gal-C-MEs) had a well-defined spherical shape with a small size (47.63 ± 1.41 nm), a narrow polydispersity index (PDI, 0.101 ± 0.002), and a nearly neutral surface charge (-4.37 ± 1.76 mV). The half-maximal inhibitory concentration (IC50) of Gal-C-MEs against HepG2 cells was 70.2 μg/mL, which decreased by 1.8-fold in comparison with that of coix seed multicomponent microemulsions (C-MEs). The fluorescence intensity of fluorescein isothiocyanate (FITC)-loaded Gal-C-MEs (FITC-Gal-C-MEs) internalized by HepG2 cells was 1.8-fold higher than that of FITC-loaded C-MEs (FIT C-C-MEs), but the cellular uptake of the latter became reduce by 1.6-fold when the weight ratio of CP decreased up to 10%. In the cell apoptosis studies, C-MEs (containing 30% CP) did not show a significant difference with Gal-C-MEs, but exhibited 3.3-fold and 1.5-fold increase relative to C-MEs containing 10% CP and 20% CP, respectively. In the in vivo tumor targeting studies, Cy5-loaded Gal-C-MEs (Cy5-Gal-C-MEs), notably distributed in the tumor sites and still found even at 48 h post-administration, displayed the strongest capability of tumor tissue accumulation and retention among all the test groups. Most importantly, Gal-C-MEs had stronger inhibition of tumor growth, prolonged survival time and more effectively tumor cell apoptosis induction in comparison with C-MEs containing different amounts of CP, which further confirmed that a certain amount of CP and tumor-targeted ligand were of great importance to

  15. Raman imaging of polymer gels and elastomer blends

    NASA Astrophysics Data System (ADS)

    Appel, Rainer

    2000-12-01

    The incorporation of high-resolution optics in a Raman spectrometer allows sampling from areas less than one micron in diameter. The addition of a confocal microscope improves the axial resolution to a couple of microns. The fast data collection combined with high lateral and vertical resolutions makes possible scanning experiments in which the specimen is advanced in micron size steps. Analysis of the spectra provides information on the spatial composition of the sample. For macroporous N-isopropylacrylamide (NIPA) gel the temperature induced evolution of the pore structures is characterized. This model is used to explain surface roughness of the gels and characteristics of a NIPA- acrylamide (PAAM) interface. At room temperature, the average sizes of the pores and the width of polymer-rich areas are 75 μm and 20 μm, respectively. At higher temperatures polymer chains bunch together and this process accelerates rapidly near the volume phase transition temperature (34°C). The porous structure of the NIPA extends to the gel's boundary causing surface roughness, which, like the bulk material, is temperature dependent. A shrinking process results in a dense shell on the surface. Also, the surface becomes smoother due to hydrophobic interactions between isopropyl groups in the NIPA gel. For a polymer-polymer interface we showed that different drying and diffusion times affect the topography of the interfacial region. Phase separation in binary mixtures of two polymers, polyisobutadiene (BR) and brominated poly(isobuthylene- co-para-methylstyrene) (BIMS), is studied for different compositions of the blends. Binary blends of BIMS and BR do mix better in the presence of precipitated silica and domain sizes decrease from approximate 5 μm to less than 1μm. Blend components with polar groups like BIMS, silica, and zinc stearate can be found in close proximity to each other. The blend morphology of the uncured samples is dependent upon temperature. Increased temperature

  16. Cryo-TEM of morphology and kinetics of self-assembled nanostructures

    NASA Astrophysics Data System (ADS)

    Dong, Jingshan

    Cryogenic Transmission Electron Microscopy (Cryo-TEM) is applied to study various structures in solutions and suspensions from micron to nanometer scale. By vitrifying the liquid samples at different moments, sequential stages of a dynamic process can be frozen and the structures occurring from about 30 sec to over 10 min can be imaged. Therefore a picture of how the structures evolve with time in the liquid systems can be established. This method has been proven to be a powerful technique in studying the morphology and kinetics of self-assembled nanostructures. Such a pseudo-in-situ technique is used to "watch" the crystallization process of silver stearate (AgSt) from sodium stearate (NaSt) dispersions. AgSt crystal is produced from a reaction of NaSt and silver nitrate. The reaction, as a AgSt crystallization process, starts from AgSt micelles, which aggregate and grow into hexagonal shaped crystals of about 10 microns. If silver bromide (AgBr) grains are present, the micelles do not prefer to aggregate, but rather deposit on the surface of the AgBr crystalline grains. Variation of the carboxylate chain length does not affect the crystallization process very much, although the morphology of both the reactant and the product is changed. Nanostructure transition in sodium lauryl ether sulfate (SLES) solutions is investigated as well. A micellar network structure can form if equal molar calcium chloride is added to 3 wt% SLES solution. The network can be broken into wormlike micelle segments such as spheres and rods by sonication. After about 10 min, these broken pieces can reassemble and reform the network through wormlike micelle growth and connection. Also by using Cryo-TEM, 100-200 nm casein micelles are observed at 1 wt% casein solution, but aggregated submicelles cannot be distinguished. However, individual submicelles of about 30 nm are indeed captured in a 0.03 wt% solution. By adding acid or EDTA, the casein micelles can be disrupted into small particles

  17. Layer-by-layer assembled composite films of side-functionalized poly(3-hexylthiophene) and CdSe nanocrystals: electrochemical, spectroelectrochemical and photovoltaic properties.

    PubMed

    De Girolamo, Julia; Reiss, Peter; Zagorska, Malgorzata; De Bettignies, Remi; Bailly, Severine; Mevellec, Jean-Yves; Lefrant, Serge; Travers, Jean-Pierre; Pron, Adam

    2008-07-21

    Regioregular poly(3-hexylthiophene) containing one diaminopyrimidine side group per ten repeat units (P3HT-co-P3(ODAP)HT) can form molecular composites with 1-(6-mercaptohexyl)thymine capped CdSe nanocrystals (CdSe(MHT)) via hydrogen bonds directed molecular recognition. Here we report complementary spectroscopic, electrochemical and spectroelectrochemical investigations of both the functionalized poly(thiophene) and its composite with the nanocrystals, the latter being fabricated using the layer-by-layer (LbL) deposition technique. UV-Vis-NIR and Raman spectroelectrochemical investigations unequivocally show that the onset of the first anodic peak in the cyclic voltammogram of the copolymer can be attributed to the oxidation of the pi-conjugated backbone in the polymer chains. For this reason, it is possible to determine the width and the position of its band gap (corresponding to the pi-pi* transition) by UV-Vis spectroscopy combined with cyclic voltammetry. These studies show that the polymer exhibits a slightly larger band gap with the HOMO level insignificantly lower in energy (by 0.03 eV) as compared to the case of regioregular poly(3-hexylthiophene) of comparable degree of polymerization. Hydrogen bond interactions of the polymer with CdSe(MHT) in the molecular composite result in a hypsochromic shift of the band corresponding to the pi-pi* transition from 504 nm to 488 nm. This can be taken as a spectroscopic manifestation of the conformational changes induced by shortening of the conjugation length. The observed spectral modifications are consistent with electrochemically determined lowering of the polymer HOMO level (from -4.91 eV in the pure polymer to -4.99 eV in the composite). Cyclic voltammetry studies supported by spectroelectrochemistry also show that the redox stability of CdSe(MHT) in the molecular composite with P3HT-co-P3(ODAP)HT is lower than that determined for stearate-capped nanocrystals. Their irreversible oxidation starts at E = +0.7 V vs

  18. Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process.

    PubMed

    Nozawa, Kenji; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2015-11-10

    To generate products containing a stable form of clarithromycin (CAM) (form II) regardless of the initial crystal form of CAM or type of granulation solvent, the effects of five surfactants, or a water-soluble polymer (macrogol 400) were determined on the crystal transition of CAM. The metastable form (form I) was kneaded with water, after adding surfactants, or a water-soluble polymer. Form II was also kneaded with ethanol, after adding the same additives. The resulting samples were analyzed by powder X-ray diffraction. Form I was completely converted to form II by a wet granulation using water with additives bearing polyoxyethylene chains such as polysorbate 80 (PS80), polyoxyl 40 stearate or macrogol 400. The granulation of the form II using ethanol with these additives did not result in a crystal transition to form I. Furthermore, CAM tablets were manufactured using granules with PS80, and these crystal forms and dissolution behaviors were investigated. As a result, the wet granulation of CAM with PS80 gave CAM tablets containing only form II and PS80 did not have any adverse effects on tablet characteristics. Therefore, these data suggests that the crystal form of CAM can be controlled to be form II using a wet granulation process with additives bearing polyoxyethylene chains regardless of the initial crystal form of CAM or type of granulation solvent. PMID:26325306

  19. Excipient-process interactions and their impact on tablet compaction and film coating.

    PubMed

    Pandey, Preetanshu; Bindra, Dilbir S; Gour, Shruti; Trinh, Jade; Buckley, David; Badawy, Sherif

    2014-11-01

    The objective of this study was to establish the effects of the level of minor formulation components (sodium lauryl sulfate: SLS, and magnesium stearate: MgSt) and manufacturing process on final blend compaction properties and the performance of the tablets during film coating. A 2 × 2 × 3 factorial study was conducted at two levels of SLS (0% and 1%, w/w) and MgSt (0.5% and 1.75%, w/w), along with three different manufacturing processes (direct compression, high-shear wet granulation, and dry granulation). The tablets were compressed to the same solid fraction (0.9) and the resulting tablet hardness values were found to vary over a range of 13-42 SCU, highlighting large compactability differences among these batches. Increase in the level of SLS or MgSt in the formulation had a significant negative effect on compactability and the performance of film-coated tablets. The detrimental effects on compaction and coating performance were magnified for the dry granulation process, likely due to the overall increased shear experienced by excipients (SLS, MgSt, microcrystalline cellulose) during the roller compaction and milling steps. The findings of this study highlight the importance of the manufacturing process when considering the use-level of formulation components such as SLS and MgSt in the formulation. PMID:25223603

  20. Formulation and stability evaluation of immediate release antioxidant tablet.

    PubMed

    Sultana, Abida; Hassan, Fouzia; Israr, Fozia; Hasan, S M Farid; Haque, Naheed

    2014-09-01

    Oxidative stress plays an important part in the development of human diseases. Pharmaceutical strategies are required to be work out in order to fight against such oxidative damages. Designing of new formulations that can protect human beings from the undesirable effects, consequence of oxidative stress, the crucial cellular and molecular processes, along with recurring oxidative damage and diseases is to be expedited. The main objective of present work was to design a rapidly releasing synthetic antioxidant tablet dosage form comprising of vitamin A, vitamin C, vitamin E and zinc in combination with lecithin (a phospho-lipid) that can fulfill human health and nutritional requirement and to perform stability studies. Beside active ingredients, the excipients used in present formulation were; Avicel pH 102, starch pregelatinized, silicon dioxide colloidal and polyethylene glycol 8000 milled magnesium stearate, acid stearic fine powder and aq.opa dry coating material. The immediate release formulation of antioxidant was prepared by wet granulation method. Three different trials were developed. Vitamin C was selected as tracer for detection and evaluation of tablet dosage form. When the resulting formulation was evaluated by USP 24 / NF 19, 2000 guidelines and later by stability studies, it was found that their quality can be maintained over a storage period of 24 months. PMID:25176233

  1. Aging Studies of VCE Dismantlement Returns

    SciTech Connect

    Letant, S; Alviso, C; Pearson, M; Albo, R; Small, W; Wilson, T; Chinn, S; Maxwell, R

    2011-10-17

    VCE is an ethylene/vinyl acetate/vinyl alcohol terpolymer binder for filled elastomers which is designed to accept high filler loadings. Filled elastomer parts consist of the binder (VCE), a curing agent (Hylene MP, diphenol-4-4{prime}-methylenebis(phenylcarbamate)), a processing aid (LS, lithium stearate), and filler particles (typically 70% fraction by weight). The curing of the filled elastomer parts occurs from the heat-activated reaction between the hydroxyl groups of VCE with the Hylene MP curing agent, resulting in a cross-linked network. The final vinyl acetate content is typically between 34.9 and 37.9%, while the vinyl alcohol content is typically between 1.27 and 1.78%. Surveillance data for this material is both scarce and scattered, complicating the assessment of any aging trends in systems. In addition, most of the initial surveillance efforts focused on mechanical properties such as hardness and tensile strength, and chemical information is therefore lacking. Material characterization and aging studies had been performed on previous formulations of the VCE material but the Ethylene Vinyl Acetate (EVA) starting copolymer is no longer commercially available. New formulations with replacement EVA materials are currently being established and will require characterization as well as updated aging models.

  2. Uptake of all-trans retinoic acid–containing aerosol by inhalation to lungs in a guinea pig model system—A pilot study

    PubMed Central

    Schäffer, Michael W.; Roy, Somdutta Sinha; Mukherjee, Shyamali; Ong, David E.; Das, Salil K.

    2010-01-01

    Systemic therapies with retinoic acid (RA) can result in toxic side effects without yielding biologically effective levels in target tissues such as lung. The authors adapted a PARI LC Star nebulizer to create a tubular system for short-term inhalation treatment of guinea pigs using a water-miscible formulation of all-trans RA (ATRA) or vehicle. Based on the initial average weight, animals received an estimated average ATRA doses of either 0.32 mg·kg−1 (low dose, 1.4 mM), or 0.62 mg·kg−1 (medium dose, 2.8 mM), or 1.26 mg·kg−1 (high dose, 5.6 mM) 20 minutes per day for 6 consecutive days. This system led to a rise of ATRA levels in lung, but not liver or plasma. Cellular lung levels of retinol, retinyl palmitate, and retinyl stearate also appeared to be unaffected (245.6 ± 10.7, 47.4 ± 3.4, and 132.8 ± 7.7 ng·g−1 wet weight, respectively). The application of this aerosolized ATRA also induced a dose-dependent protein expression of the cellular retinol-binding protein 1 (CRBP-1) in lung, without apparent harmful side effects. PMID:21043991

  3. Collapse of Langmuir monolayer at lower surface pressure: Effect of hydrophobic chain length

    NASA Astrophysics Data System (ADS)

    Das, Kaushik; Kundu, Sarathi

    2016-05-01

    Long chain fatty acid molecules (e.g., stearic and behenic acids) form a monolayer on water surface in the presence of Ba2+ ions at low subphase pH (≈ 5.5) and remain as a monolayer before collapse generally occurs at higher surface pressure (πc > 50 mN/m). Monolayer formation is verified from the surface pressure vs. area per molecule (π-A) isotherms and also from the atomic force microscopy (AFM) analysis of the films deposited by single upstroke of hydrophilic Si (001) substrate through the monolayer covered water surface. At high subphase pH (≈ 9.5), barium stearate molecules form multilayer structure at lower surface pressure which is verified from the π-A isotherms and AFM analysis of the film deposited at 25 mN/m. Such monolayer to multilayer structure formation or monolayer collapse at lower surface pressure is unusual as at this surface pressure generally fatty acid salt molecules form a monolayer on the water surface. Formation of bidentate chelate coordination in the metal containing headgroups is the reason for such monolayer to multilayer transition. However, for longer chain barium behenate molecules only monolayer structure is maintained at that high subphase pH (≈ 9.5) due to the presence of relatively more tail-tail hydrophobic interaction.

  4. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect.

    PubMed

    Niculae, G; Lacatusu, I; Badea, N; Meghea, A

    2012-08-10

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions. PMID:22797534

  5. Non-invasive characterization of the adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells by HS-SPME/GC-MS

    PubMed Central

    Lee, Dong-Kyu; Yi, TacGhee; Park, Kyung-Eun; Lee, Hyun-Joo; Cho, Yun-Kyoung; Lee, Seul Ji; Lee, Jeongmi; Park, Jeong Hill; Lee, Mi-Young; Song, Sun U.; Kwon, Sung Won

    2014-01-01

    A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells. PMID:25298091

  6. A fluorescence study of A23187 interaction with phospholipid vesicles

    SciTech Connect

    Puskin, J.S.; Vistnes, A.I.; Coene, M.T.

    1981-01-01

    The fluorescence of the ionophore A23187 has been monitored in suspensions of egg yolk phosphatidylcholine (EYPC) and dipalmitoyl phosphatidylcholine (DPPC) vesicles. Both the protonated form of A23187 and the Ca/sup 2 +/ complex exhibit fluorescence enhancement when extracted into a hydrophobic environment. Measurements of fluorescence intensity versus lipid concentration were thus used to establish lower limits to the lipid/water partition coefficients. Values obtained in this way were greater than or equal to50 ml water/mg phosphatidylcholine. Quenching of A23187 fluorescence by the spin labels 5NMS (methyl ester of 5-nitroxyl stearate), 12NMS, 16NMS, and TEMPO stearamide in EYPC and DPPC vesicles was also investigated. In EYPC all the labels yielded fairly linear Stern-Volmer plots, with TEMPO stearamide quenching about half as strong as the other probes. Quenching in DPPC was generally much stronger than in EYPC, but 12 NMS and 16NMS gave hyperbolic Stern-Volmer plots, apparently due to clustering of the labels. In all the cases the protonated form of A23187 was quenched approximately twice as efficiently as the Ca/sup 2 +/ complex, possibly due to a longer fluorescence lifetime for the former. Calculations based on measured spectral properties were performed which indicate that the Forster transfer mechanism extends the nitroxides' quenching range to approximately 10 angstrom.

  7. A method to evaluate the effect of contact with excipients on the surface crystallization of amorphous drugs.

    PubMed

    Zhang, Si-Wei; Yu, Lian; Huang, Jun; Hussain, Munir A; Derdour, Lotfi; Qian, Feng; de Villiers, Melgardt M

    2014-12-01

    Amorphous drugs are used to improve the solubility, dissolution, and bioavailability of drugs. However, these metastable forms of drugs can transform into more stable, less soluble, crystalline counterparts. This study reports a method for evaluating the effect of commonly used excipients on the surface crystallization of amorphous drugs and its application to two model amorphous compounds, nifedipine and indomethacin. In this method, amorphous samples of the drugs were covered by excipients and stored in controlled environments. An inverted light microscope was used to measure in real time the rates of surface crystal nucleation and growth. For nifedipine, vacuum-dried microcrystalline cellulose and lactose monohydrate increased the nucleation rate of the β polymorph from two to five times when samples were stored in a desiccator, while D-mannitol and magnesium stearate increased the nucleation rate 50 times. At 50% relative humidity, the nucleation rates were further increased, suggesting that moisture played an important role in the crystallization caused by the excipients. The effect of excipients on the crystal growth rate was not significant, suggesting that contact with excipients influences the physical stability of amorphous nifedipine mainly through the effect on crystal nucleation. This effect seems to be drug specific because for two polymorphs of indomethacin, no significant change in the nucleation rate was observed under the excipients. PMID:25037732

  8. Influence of excipients in comilling on mitigating milling-induced amorphization or structural disorder of crystalline pharmaceutical actives.

    PubMed

    Balani, Prashant N; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung

    2010-05-01

    The feasibility of using excipients to suppress the amorphization or structural disorder of crystalline salbutamol sulphate (SS) during milling was investigated. SS was subjected to ball-milling in the presence of alpha-lactose monohydrate (LAC), adipic acid (AA), magnesium stearate (MgSt), or polyvinyl pyrrolidone (PVP). X-ray powder diffraction, dynamic vapor sorption (DVS), high sensitivity differential scanning calorimetry (HSDSC) were used to analyze the crystallinity of the milled mixtures. Comilling with crystalline excipients, LAC, AA, and MgSt proved effective in reducing the amorphization of SS. LAC, AA, or MgSt acting as seed crystals to induce recrystallization of amorphous SS formed by milling. During comilling, both SS and LAC turned predominantly amorphous after 45 min but transformed back to a highly crystalline state after 60 min. Amorphous content was below the detection limits of DVS (0.5%) and HSDSC (5%). Comilled and physical mixtures of SS and ALM were stored under normal and elevated humidity conditions. This was found to prevent subsequent changes in crystallinity and morphology of comilled SS:LAC as compared to significant changes in milled SS and physical mixture. These results demonstrate a promising application of comilling with crystalline excipients in mitigating milling induced amorphization of pharmaceutical actives. PMID:19902526

  9. Purification and specificity of lipases fromGeotrichum candidum.

    PubMed

    Baillargeon, M W

    1990-12-01

    A crude, commercialGeotrichum candidum lipase (EC 3.1.1.3) preparation (Amano GC-20) was purified by hydrophobic interaction chromatography on Octyl Sepharose. The purified enzyme is a microheterogeneous glycoprotein containing isozymes varying in molecular weight, pI and specificity. It consists of 64, 62 and 59 kDa species as determined by denaturing polyacrylamide gel electrophoresis. Five isozymes (pI 4.40, 4.47, 4.58, 4.67 and 4.72) are detected by isoelectric focusing using both silver and activity stains. Chromatofocusing was used to separate the isozymes according to pI. Although all the isozymes are specific for oleatevs stearate esters, one isozyme (pI 4.72) is also specific for oleatevs palmitate. The number of isozymes is reduced to two (pI 4.67 and 4.72) after carbohydrate removal using endoglycosidase F/N-glycosidase. These isozymes may be products of two lipase genes. PMID:27520688

  10. Treatment with coated layer double hydroxide clays decreases the toxicity of copper-contaminated water.

    PubMed

    Blake, Deanne; Nar, Mangesh; D'Souza, Nandika Anne; Glenn, J Brad; Klaine, Stephen J; Roberts, Aaron P

    2014-05-01

    Copper is a common pollutant found in watersheds that exerts toxic effects on both invertebrates and vertebrates. Layer double hydroxide (LDH) clays are able to adsorb a wide range of contaminants through ion-exchange mechanisms. Coating LDH clays with various materials alters the aggregation of clay particles into the nano-size range, thus increasing relative surface area and offering great potential for contaminant remediation. The goal of this study was to determine if treatment with coated LDH clays decreases the toxicity of copper-containing solutions to Daphnia magna. Four LDH clays with different coatings used to alter hydrophobicity were as follows: used: Na(+) montmorillonite, Zn-Al LDH-nitrate, Zn-Al LDH-stearate, and Zn-Al LDH-carbonate. It was determined that coated LDH clays decreased copper toxicity by decreasing bioavailability and that smaller aggregate sizes decreased bioavailability the most. 96 h LC50 values increased by as much as 4.2 times with the treatment of the solutions with 100 mg/L LDH clay. Copper analysis of the clay and solutions indicated that the clays work by decreasing copper bioavailability by way of a binding mechanism. Coated LDH clays hold promise as a small-scale remediation tool or as an innovative tool for toxicity identification and evaluation characterization of metals. PMID:24442186

  11. Effects of selected polysorbate and sucrose ester emulsifiers on the physicochemical properties of astaxanthin nanodispersions.

    PubMed

    Anarjan, Navideh; Tan, Chin Ping

    2013-01-01

    The effects of selected nonionic emulsifiers on the physicochemical characteristics of astaxanthin nanodispersions produced by an emulsification/evaporation technique were studied. The emulsifiers used were polysorbates (Polysorbate 20, Polysorbate 40, Polysorbate 60 and Polysorbate 80) and sucrose esters of fatty acids (sucrose laurate, palmitate, stearate and oleate). The mean particle diameters of the nanodispersions ranged from 70 nm to 150 nm, depending on the emulsifier used. In the prepared nanodispersions, the astaxanthin particle diameter decreased with increasing emulsifier hydrophilicity and decreasing carbon number of the fatty acid in the emulsifier structure. Astaxanthin nanodispersions with the smallest particle diameters were produced with Polysorbate 20 and sucrose laurate among the polysorbates and the sucrose esters, respectively. We also found that the Polysorbate 80- and sucrose oleate-stabilized nanodispersions had the highest astaxanthin losses (i.e., the lowest astaxanthin contents in the final products) among the nanodispersions. This work demonstrated the importance of emulsifier type in determining the physicochemical characteristics of astaxanthin nano-dispersions. PMID:23303336

  12. Investigation of triacetin effect on indomethacin release from poly(methyl methacrylate) microspheres: evaluation of interactions using FT-IR and NMR spectroscopies.

    PubMed

    Yuksel, Nilufer; Baykara, Meltem; Shirinzade, Hanif; Suzen, Sibel

    2011-02-14

    The purpose of this study was to form indomethacin (IND)-loaded poly(methyl methacrylate) (PMMA) microspheres having an extended drug release profile over a period of 24h. Microspheres were prepared by solvent evaporation method using sucrose stearate as a droplet stabilizer. When PMMA was used alone for the preparation of microspheres, only 44% of IND could be released at the end of 8h. Triacetin was added to PMMA, as a minor phase, and the obtained microspheres showed a high yield process with recovery of 89.82% and incorporation efficiency of 102.3%. A desired release profile lasting 24h was achieved. Differential scanning calorimetry (DSC) analysis showed that IND was found to be in an amorphous state in the microspheres. Fourier transform infrared (FT-IR) and nuclear magnetic resonance ((1)H NMR) spectra suggested that there might be a hydrogen bond present between the IND hydroxyl group and PMMA. No interaction between triacetin and IND or PMMA as the formation of secondary bonds was observed. The release enhancement of IND from microspheres was attributed to the physical plasticization effect of triacetin on PMMA and, to some extent, the amorphous state of the drug. PMID:21093553

  13. Modelling of the solvent evaporation method for the preparation of controlled release acrylic microspheres using neural networks.

    PubMed

    Yüksel, N; Türkoglu, M; Baykara, T

    2000-01-01

    The purpose of the present study was to model the solvent evaporation procedure for the preparation of acrylic microspheres by using artificial neural networks (ANNs) to obtain an understanding of the selected preparative variables. Three preparative variables, the concentration of the dispersing agent (sucrose stearate), the stirring rate of emulsion system, and the ratio of polymers (Eudragit RS-L) were studied, each at different levels, as input variables. The response (output) variables examined to characterize microspheres and drug release were the size of the microspheres and T63.2%, the time at which 63.2% of drug is released. The results were also analysed by the multiple linear regression (MLR) to provide a comparison with the ANN methodology. Although both ANN and MLR methods were found to be similar in characterizing the process studied, the results showed that an ANN method gave a better prediction than the MLR method. For the size values of the microspheres, the predictability of the ANN model was quite high (R2 = 0.9602) based on the input variables. A relationship between these variables and size values of microspheres was also obtained by the MLR model (R2 = 0.9050). The performances of both models for the release data from microspheres based on the same input variables were at the level of 53%. According to the results, the ANN methodology can provide an alternative to the traditional regression methods, as a flexible and accurate method to study process and formulation factors. PMID:11038114

  14. Non-invasive characterization of the adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells by HS-SPME/GC-MS.

    PubMed

    Lee, Dong-Kyu; Yi, TacGhee; Park, Kyung-Eun; Lee, Hyun-Joo; Cho, Yun-Kyoung; Lee, Seul Ji; Lee, Jeongmi; Park, Jeong Hill; Lee, Mi-Young; Song, Sun U; Kwon, Sung Won

    2014-01-01

    A non-invasive method to characterize human mesenchymal stromal cells during adipogenic differentiation was developed for the first time. Seven fatty acid methyl esters (FAMEs), including methyl laurate, methyl myristate, methyl palmitate, methyl linoleate, methyl oleate, methyl elaidate and methyl stearate, were used for characterizing adipogenic differentiation using headspace solid-phase microextraction (HS-SPME) which is a very simple and non-invasive method for the extraction of volatile compounds. Glassware was used for culturing mesenchymal stromal cells rather than the common plasticware to minimize contamination by volatile impurities. The optimal SPME fiber was selected by comparing diverse fibers containing two pure liquid polymers (PDMS and PA) and two porous solids (PDMS/DVB and CAR/PDMS). Using optimized procedures, we discovered that seven FAMEs were only detected in adipogenic differentiated mesenchymal stromal cells and not in the mesenchymal stromal cells before differentiation. These data could support the quality control of clinical mesenchymal stromal cell culture in the pharmaceutical industry in addition to the development of many clinical applications using mesenchymal stromal cells. PMID:25298091

  15. Measurement of optical anisotropy in ultrathin films using surface plasmon resonance

    NASA Astrophysics Data System (ADS)

    Devanarayanan, V. P.; Manjuladevi, V.; Poonia, Monika; Gupta, R. K.; Gupta, Sanjeev K.; Akhtar, Jamil

    2016-01-01

    The optical phenomenon, surface plasmon resonance (SPR) is employed for the measurement of optical anisotropy in the ultrathin films fabricated through Langmuir-Blodgett (LB) and self-assembled monolayer (SAM) techniques onto 50 nm gold film supported on BK7 glass substrates. The resonance angle (RA) is measured using a home built setup in Kretschmann configuration. The LB films and SAM can provide a single layer of highly ordered and organized molecules on the two dimensional surface. If the film forming molecules are anisotropic, their organization in the LB films and SAM can yield an anisotropic film due to tilt of the molecules with respect to the surface normal. The SPR spectra are recorded for the two orthogonal directions of the film with respect to the plane of incidence. The spectra are simulated by modeling the Fresnel's reflection from 4-layers viz., prism, gold, ultrathin films and air; and the real and imaginary parts of refractive index are estimated. Our study shows the metallic and dielectric nature of the LB films of bundles of single walled carbon nanotubes (SWCNTs) when the long axis of SWCNTs are aligned parallel and perpendicular to plane of incidence, respectively. The optical anisotropy was estimated from the change in real part of refractive index (Δnr) of the ultrathin films measured in the orthogonal directions. In addition, we have also studied such optical anisotropy in the LB film of cadmium-stearate and self-assembled monolayer of octadecanethiol.

  16. Thin coatings based on ZnO@C18-usnic acid nanoparticles prepared by MAPLE inhibit the development of Salmonella enterica early biofilm growth

    NASA Astrophysics Data System (ADS)

    Stan, Miruna Silvia; Constanda, Sabrina; Grumezescu, Valentina; Andronescu, Ecaterina; Ene, Ana Maria; Holban, Alina Maria; Vasile, Bogdan Stefan; Mogoantă, Laurenţiu; Bălşeanu, Tudor-Adrian; Mogoşanu, George Dan; Socol, Gabriel; Grumezescu, Alexandru Mihai; Dinischiotu, Anca; Lazar, Veronica; Chifiriuc, Mariana Carmen

    2016-06-01

    The aim of this study was to develop a nanostructured bioactive surface based on zinc oxide, sodium stearate (C18) and usnic acid (UA) exhibiting harmless effects with respect to the human cells, but with a significant antimicrobial effect, limiting the attachment and biofilm formation of food pathogens. ZnO nanoparticles were synthesized by sol-gel method and functionalized with C18 and UA. The coatings were fabricated by matrix assisted pulsed laser evaporation technique (MAPLE) and further characterized by TEM, SEM, SAED, XRD and IRM. The biological characterization of the prepared coatings consisted in cytotoxicity and antimicrobial assays. The cytotoxicity of ZnO@C18 and ZnO@C18-UA films was evaluated with respect to the human skin fibroblasts (CCD 1070SK cell line) by phase contrast microscopy, MTT assay and nitric oxide (NO) release. The covered surfaces exhibited a decreased cell attachment, effect which was more pronounced in the presence of UA as shown by purple formazan staining of adhered cells. The unattached fibroblasts remained viable after 24 h in the culture media as it was revealed by their morphology analysis and NO level which were similar to uncovered slides. The quantitative microbiological assays results have demonstrated that the bioactive coatings have significantly inhibited the adherence and biofilm formation of Salmonella enterica. The obtained results recommend these materials as efficient approaches in developing anti-adherent coatings for various industrial, medical and food processing applications.

  17. Engineering Multi-scale Electrospun Structure for Integration into Architected 3-D Nanofibers for Cimex Annihilation: Fabrication and Mechanism Study

    NASA Astrophysics Data System (ADS)

    He, Shan; Zhang, Linxi; Liu, Ying; Rafailovich, Miriam; Garcia Center for Polymers at Engineered Interfaces Team

    In this study, engineered electrospun scaffolds with fibers oriented with designed curvature in three dimensions (3D) including the looped structure were developed based on the principle of electrostatic repulsion. Here we illustrate that 3D electrospun recycled polystyrene fibers could closely mimic the unique architectures of multi-direction and multi-layer nano-spiderweb. In contrast to virgin PS, the recycled PS (Dart Styrofoam) are known to contain zinc stearate which acts as a surfactant resulting in higher electrical charge and larger fiber curvature, hence, lower modulus. The surfactant, which is known to decrease the surface tension, may have also been effective at decreasing the confinement of the PS, where chain stretching was shown to occur, in response to the high surface tension at the air interface. Three dimensional flexible architecture with complex structures are shown to be necessary in order to block the motion of Cimex lectularius. Here we show how an engineered electrospun network of surfactant modified polymer fibers with calculated dimensions can be used to immobilize the insects. The mechanical response of the fibers has to be specifically tailored so that it is elastically deformed, without fracturing or flowing. Carefully controlling and tailoring the electrospinning parameters we can now utilize architected 3D nanofiber to create an environmental-friendly Cimex immobilization device which can lead to annihilation solution for all the other harmful insects.

  18. Data from mass spectrometry, NMR spectra, GC-MS of fatty acid esters produced by Lasiodiplodia theobromae.

    PubMed

    Uranga, Carla C; Beld, Joris; Mrse, Anthony; Córdova-Guerrero, Iván; Burkart, Michael D; Hernández-Martínez, Rufina

    2016-09-01

    The data described herein is related to the article with the title "Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings" C.C. Uranga, J. Beld, A. Mrse, I. Cordova-Guerrero, M.D. Burkart, R. Hernandez-Martinez (2016) [1]. Data includes nuclear magnetic resonance spectroscopy and GC-MS data used for the identification and characterization of fatty acid esters produced by L. theobromae. GC-MS traces are also shown for incubations in defined substrate, consisting in Vogel׳s salts supplemented with either 5% grapeseed oil or 5% glucose, the two combined, or 5% fructose. Traces for incubations in the combination of 5% grapeseed oil and 5% glucose for different fungal species are also included. Images of mycelium morphology when grown in 5% glucose with or without 5% grapeseed oil are shown due to the stark difference in mycelial pigmentation in the presence of triglycerides. High concentration gradient data for the plant model Nicotiana tabacum germinated in ethyl stearate (SAEE) and ethyl linoleate (LAEE) is included to show the transition between growth inhibition and growth induction in N. tabacum by these compounds. PMID:27274528

  19. Low-temperature processed Ga-doped ZnO coatings from colloidal inks.

    PubMed

    Della Gaspera, Enrico; Bersani, Marco; Cittadini, Michela; Guglielmi, Massimo; Pagani, Diego; Noriega, Rodrigo; Mehra, Saahil; Salleo, Alberto; Martucci, Alessandro

    2013-03-01

    We present a new colloidal synthesis of gallium-doped zinc oxide nanocrystals that are transparent in the visible and absorb in the near-infrared. Thermal decomposition of zinc stearate and gallium nitrate after hot injection of the precursors in a mixture of organic amines leads to nanocrystals with tunable properties according to gallium amount. Substitutional Ga(3+) ions trigger a plasmonic resonance in the infrared region resulting from an increase in the free electrons concentration. These nanocrystals can be deposited by spin coating, drop casting, and spray coating resulting in homogeneous and high-quality thin films. The optical transmission of the Ga-ZnO nanoparticle assemblies in the visible is greater than 90%, and at the same time, the near-infrared absorption of the nanocrystals is maintained in the films as well. Several strategies to improve the films electrical and optical properties have been presented, such as UV treatments to remove the organic compounds responsible for the observed interparticle resistance and reducing atmosphere treatments on both colloidal solutions and thin films to increase the free carriers concentration, enhancing electrical conductivity and infrared absorption. The electrical resistance of the nanoparticle assemblies is about 30 kΩ/sq for the as-deposited, UV-exposed films, and it drops down to 300 Ω/sq after annealing in forming gas at 450 °C, comparable with state of the art tin-doped indium oxide coatings deposited from nanocrystal inks. PMID:23394063

  20. Solution Structures of Spinach Acyl Carrier Protein with Decanoate and Stearate†

    PubMed Central

    Zornetzer, Gregory A.; Fox, Brian G.; Markley, John L.

    2008-01-01

    Acyl carrier protein (ACP) is a cofactor in a variety of biosynthetic pathways, including fatty acid metabolism. Thus it is of interest to determine structures of physiologically relevant ACP-fatty acid complexes. We report here the NMR solution structures of spinach ACP with decanoate (10:0-ACP) and stearate (18:0-ACP) attached to the 4′ phosphopantetheine prosthetic group. The protein in the fatty acid complexes adopts a single conformer, unlike apo- and holo-ACP, which interconvert in solution between two major conformers. The protein component of both 10:0- and 18:0-ACP adopts the four-helix bundle topology characteristic of ACP, and a fatty acid binding cavity was identified in both structures. Portions of the protein close in space to the fatty acid and the 4′ phosphopantetheine were identified using filtered/edited NOESY experiments. A docking protocol was used to generate protein structures containing bound fatty acid for 10:0- and 18:0-ACP. In both cases, the predominant structure contained fatty acid bound down the center of the helical bundle, in agreement with the location of the fatty acid binding pockets. These structures demonstrate the conformational flexibility of spinach-ACP and suggest how the protein changes to accommodate its myriad binding partners. PMID:16618110

  1. Characterization Of Multilayer X-Ray Analyzers: Models And Measurements

    NASA Astrophysics Data System (ADS)

    Henke, B. L.; Uejio, J. Y.; Yamada, H. T.; Tackaberry, R. E.

    1986-08-01

    A procedure is described for a detailed characterization of multilayer analyzers that can be effectively applied to their design, optimization, and application for absolute x-ray spectrometry in the 100 to 10,000 eV photon energy region. An accurate analytical model has been developed that is based upon a simple modification of the dynamical Darwin-Prins theory to extend its application to finite multilayer systems and to the low energy x-ray region. Its equivalence to the optical E&M solution of the Fresnel equations at each interface is demonstrated by detailed comparisons for the reflectivity of a multilayer throughout the angular range of incidence of 0° to 90°. A special spectrograph and an experimental method are described for the measurement of the absolute reflectivity characteristics of the multilayer. The experimental measurements at three photon energies in the 100 to 2000 eV region are fit by the analytical modified Darwin-Prins equation (MDP) for 1(0), generating a detailed characterization of two state-of-the-art multilayers: sputtered tungsten-carbon with 2d 70 A and a molecular lead stearate with 2d 100 A. The fitting parameters that are determined by this procedure are applied to help establish the structural characteristics of these multilayers.

  2. Formulation and optimization of potassium iodide tablets

    PubMed Central

    Al-Achi, Antoine; Patel, Binit

    2014-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light. PMID:25685048

  3. Toward predicting tensile strength of pharmaceutical tablets by ultrasound measurement in continuous manufacturing.

    PubMed

    Razavi, Sonia M; Callegari, Gerardo; Drazer, German; Cuitiño, Alberto M

    2016-06-30

    An ultrasound measurement system was employed as a non-destructive method to evaluate its reliability in predicting the tensile strength of tablets and investigate the benefits of incorporating it in a continuous line, manufacturing solid dosage forms. Tablets containing lactose, acetaminophen, and magnesium stearate were manufactured continuously and in batches. The effect of two processing parameters, compaction force and level of shear strain were examined. Young's modulus and tensile strength of tablets were obtained by ultrasound and diametrical mechanical testing, respectively. It was found that as the blend was exposed to increasing levels of shear strain, the speed of sound in the tablets decreased and the tablets became both softer and mechanically weaker. Moreover, the results indicate that two separate tablet material properties (e.g., relative density and Young's modulus) are necessary in order to predict tensile strength. A strategy for hardness prediction is proposed that uses the existing models for Young's modulus and tensile strength of porous materials. Ultrasound testing was found to be very sensitive in differentiating tablets with similar formulation but produced under different processing conditions (e.g., different level of shear strain), thus, providing a fast, and non-destructive method for hardness prediction that could be incorporated to a continuous manufacturing process. PMID:27157310

  4. Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design.

    PubMed

    Isailović, Tanja; Ðorđević, Sanela; Marković, Bojan; Ranđelović, Danijela; Cekić, Nebojša; Lukić, Milica; Pantelić, Ivana; Daniels, Rolf; Savić, Snežana

    2016-01-01

    We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50°C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances. PMID:26539935

  5. Physico-chemical characterisation of surface modified particles for inhalation.

    PubMed

    Stank, Katharina; Steckel, Hartwig

    2013-05-01

    Surface modification of drugs for inhalation is a possibility to influence interparticulate forces. This can be necessary to achieve a sufficient aerosolisation during powder inhalation as the cohesiveness of the micronised drug can be reduced. In addition, the interaction with propellants in pressurised metered dose inhaler can be changed. This can be used to improve the physical stability of the suspension based formulations. A dry particle coating process was used for the alteration of particle surfaces. The blending of micronised salbutamol sulphate (SBS) with different concentrations of magnesium stearate (Mgst) or glycerol monostearate (GMS) was followed by co-milling with an air jet mill. The powder properties were characterised by SEM, EDX, laser diffraction, BET and inverse gas chromatography. Physical mixtures generated by Turbula blending were compared to co-milled samples. A slight particle size reduction was determined. The Mgst deposition on SBS particles was detected by EDX measurements. The dispersive surface energy of SBS is lowered and the energy distribution is more homogenous for the co-milled samples. This study proves the application of co-milling for surface modification in the inhalation area. PMID:23518364

  6. Simple and Green Fabrication of a Superhydrophobic Surface by One-Step Immersion for Continuous Oil/Water Separation.

    PubMed

    Zhu, Jingfang; Liu, Bin; Li, Longyang; Zeng, Zhixiang; Zhao, Wenjie; Wang, Gang; Guan, Xiaoyan

    2016-07-21

    In this paper, stainless steel meshes with superhydrophobic and superoleophilic surfaces were fabricated by rapid and simple one-step immersion in a solution containing hydrochloric acid and stearic acid. The apparent contact angles were tested by a video contact angle measurement system (CA). Field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were conducted to characterize the surface topographies and chemical compositions. The SEM results showed that mesh surfaces were covered by ferric stearate (Fe[CH3(CH2)16COO]2) with low surface energy. The CA test results showed that the mesh had a maximum apparent contact angle of 160 ± 1.0° and a sliding angle of less than 5.0° for the water droplet, whereas the apparent contact angle for the oil droplet was zero. Ultrasound oscillation and exposure tests at atmospheric conditions and immersion tests in 3.5 wt % NaCl aqueous solution were conducted to confirm the mesh with excellent superhydrophobic and superoleophilic properties. On the basis of the superhydrophobic mesh, a miniature separation device pump was designed to collect pure oil from the oil/water mixture. It showed that the device was easier and convenient. The techniques and materials presented in this work are promising for application to wastewater and oil spill treatment. PMID:27328269

  7. In vitro and in vivo evaluation of hydroxyzine hydrochloride microsponges for topical delivery.

    PubMed

    Zaki Rizkalla, Christianne Mounir; latif Aziz, Randa; Soliman, Iman Ibrahim

    2011-09-01

    Hydroxyzine HCl is used in oral formulations for the treatment of urticaria and atopic dermatitis. Dizziness, blurred vision, and anticholinergic responses, represent the most common side effects. It has been shown that controlled release of the drug from a delivery system to the skin could reduce the side effects while reducing percutaneous absorption. Therefore, the aim of the present study was to produce an effective drug-loaded dosage form that is able to control the release of hydroxyzine hydrochloride into the skin. The Microsponge Delivery System is a unique technology for the controlled release of topical agents, and it consists of porous polymeric microspheres, typically 10-50 μm in diameter, loaded with active agents. Eudragit RS-100 microsponges of the drug were prepared by the oil in an oil emulsion solvent diffusion method using acetone as dispersing solvent and liquid paraffin as the continuous medium. Magnesium stearate was added to the dispersed phase to prevent flocculation of Eudragit RS-100 microsponges. Pore inducers such as sucrose and pregelatinized starch were used to enhance the rate of drug release. Microsponges of nearly 98% encapsulation efficiency and 60-70% porosity were produced. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine-sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues. PMID:21800216

  8. Genomic Analysis of Genes Involved in the Biosynthesis of Very Long Chain Polyunsaturated Fatty Acids in Thraustochytrium sp. 26185.

    PubMed

    Zhao, Xianming; Dauenpen, Meesapyodsuk; Qu, Cunmin; Qiu, Xiao

    2016-09-01

    Thraustochytrium sp. 26185 is a marine protist that can produce a large amount of docosahexaenoic acid (DHA, 22:6n-3), an ω3 very long chain polyunsaturated fatty acid (VLCPUFA) of nutritional importance. However, the mechanism of how this fatty acid is synthesized and assembled into the storage lipid triacylglycerol is unclear. Here we report sequencing of the whole genome and genomic analysis of genes involved in the biosynthesis and assembly of the fatty acids in this species. Genome sequencing produced a total of 2,418,734,139 bp clean sequences with about 62 fold genome coverage. Annotation of the genome sequences revealed 10,797 coding genes. Among them, 10,216 genes could be assigned into 25 KOG classes where 451 genes were specifically assigned to the group of lipid transport and metabolism. Detailed analysis of these genes revealed co-existence of both aerobic pathway and anaerobic pathways for the biosynthesis of DHA in this species. However, in the aerobic pathway, a key gene encoding stearate Δ9 desaturase introducing the first double bond to long chain saturated fatty acid 18:0 was missing from the genome. Genomic survey of genes involved in the acyl trafficking among glycerolipids showed that, unlike plants, this protist did not possess phosphatidylcholine:diacylglycerol cholinephosphotransferase, an important enzyme in bridging two types of glycerolipids, diacylglycerols (DAG) and phosphatidylcholines (PtdCho). These results shed new insight on the biosynthesis and assembly of VLCPUFA in the Thraustochytrium. PMID:27514858

  9. Phosphatidylglycerol and Chilling Sensitivity in Plants

    PubMed Central

    Roughan, P. Grattan

    1985-01-01

    The hypothesis that molecular species of thylakoid phosphatidylglycerol containing two saturated fatty acids (disaturated phosphatidylglycerol) confer chilling sensitivity upon plants was tested by analyzing the fatty acid composition of phosphatidylglycerols isolated from leaves of a range of plants expected to have different sensitivities to chilling temperatures. `Saturated' fatty acids (palmitate plus stearate plus hexadeca-trans-3-enoate) as a proportion of total phosphatidylglycerol fatty acids varied from 51 to 80 mole per cent in the plants analyzed but appeared to be rigidly fixed for a given plant species, being unaffected by leaf maturity or by environment. Hexadeca-trans-3-enoate occurred only at the sn-2 position, whereas C-18 fatty acids occurred only at the sn-1 position of thylakoid phosphatidylglycerol. Therefore, the proportion of disaturated molecular species could be predicted accurately from the total fatty acids of phosphatidylglycerol. Disaturated molecular species accounted for <25% of the total phosphatidylglycerol from leaves of chilling-resistant plants and for 50 to 60% of the phosphatidylglycerol in leaves from some of the most chilling-sensitive plants. However, not all chilling-sensitive plants contained high proportions of disaturated phosphatidylglycerol; solanaceous and other 16:3-plants and C4 grasses may be important exceptions. Nonetheless, proportions of disaturated phosphatidylglycerol increased concomitantly with increasing chilling sensitivity of plants within a genus. PMID:16664127

  10. Energy-based analysis of cone milling process for the comminution of roller compacted flakes.

    PubMed

    Samanta, Asim Kumar; Wang, Likun; Ng, Ka Yun; Heng, Paul Wan Sia

    2014-02-28

    Cone mill is commonly used for the milling of wet and dry agglomerates in the pharmaceutical industry as it is capable of producing milled granules with desired size characteristics. The aim of this study was to evaluate the various cone mill process parameters in terms of milling rate and energy consumption for the comminution of roller compacted flakes. A placebo formulation containing microcrystalline cellulose, lactose and magnesium stearate was used to evaluate the milling performance. Results of this study showed that higher milling rate was obtained with the combination of higher impeller speed, teethed round sidearm impeller and grater screen surface profile. Either one of the later two parameters when present in any mill setting was found to be capable of shortening the residence time of flakes inside the milling chamber, thus resulting in a higher milling rate. On the other hand, selection of appropriate screen surface profile and impeller speed was very important at lowering the effective specific energy consumption during milling. Grater screen surface profile and impeller speed between 2000 and 2400 rpm were found to act synergistically as the best combination for an energy sparing process. Impeller sidearm shape was found to have no significant effect on energy consumption. PMID:24374608

  11. Evaluation of certain food additives and contaminants. Eightieth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2016-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives and contaminants and to prepare specifications for identity and purity. The first part of the report contains a brief description of general considerations addressed at the meeting, including updates on matters of interest to the work of the Committee. A summary follows of the Committee's evaluations of technical, toxicological and/or dietary exposure data for seven food additives (benzoates; lipase from Fusarium heterosporum expressed in Ogataea polymorpha; magnesium stearate; maltotetraohydrolase from Pseudomonas stutzeri expressed in Bacillus licheniformis; mixed β-glucanase, cellulase and xylanase from Rasamsonia emersonii; mixed β-glucanase and xylanase from Disporotrichum dimorphosporum; polyvinyl alcohol (PVA)- polyethylene glycol (PEG) graft copolymer) and two groups of contaminants (non-dioxin-like polychlorinated biphenyls and pyrrolizidine alkaloids). Specifications for the following food additives were revised or withdrawn: advantame; annatto extracts (solavnt extracted bixin, ad solvent-extracted norbixin); food additives containing aluminium and/or silicon (aluminium silicate; calcium aluminium silicate; calcium silicate; silicon dioxide, amorphous; sodium aluminium silicate); and glycerol ester of gum rosin. Annexed to the report are tables or text summarizing the toxicological and dietary exposure information and information on specifications as well as the Committees recommendations on the food additives and contaminants considered at this meeting. PMID:27514183

  12. Enhanced bactericidal activity of enterocin AS-48 in combination with essential oils, natural bioactive compounds and chemical preservatives against Listeria monocytogenes in ready-to-eat salad.

    PubMed

    Antonio, Cobo Molinos; Abriouel, Hikmate; López, Rosario Lucas; Omar, Nabil Ben; Valdivia, Eva; Gálvez, Antonio

    2009-09-01

    Enterocin AS-48 (30-60 microg/g) significantly reduced viable counts of Listeria monocytogenes in Russian-type salad during one week storage at 10 degrees C. Antilisterial activity of AS-48 (30 microg/g) in salad was strongly enhanced by essential oils (thyme verbena, thyme red, Spanish oregano, ajowan, tea tree, clove, and sage oils tested at 1%, as well as with 2% rosemary oil). Antilisterial activity also increased in combination with bioactive components from essential oils and plant extracts, with other related antimicrobials of natural origin or derived from chemical synthesis (carvacrol, eugenol, thymol, terpineol, tyrosol, hydroxytyrosol, caffeic, ferulic and vanillic acid, luteolin, geranyl butyrate, geranyl phenylacetate, pyrocatechol, hydrocinnamic acid, tert butylhydroquinone, phenylphosphate, isopropyl methyl phenol, coumaric acid, and 2-nitropropanol), and with food preservatives (citric and lactic acid, sucrose palmitate, sucrose stearate, p-hydroxybenzoic methylester acid -- PHBME, and Nisaplin). AS-48 acted synergistically with citric, lactic acid, and PHBME. A mixed population of two L. monocytogenes strains was markedly reduced for one week in salads treated with AS-48 (30 microg/g) in combination with lactic acid, PHBME or Nisaplin. The increased bactericidal activity of these combinations is interesting to improve protection against L. monocytogenes during salad storage. PMID:19520136

  13. Long Chain (C20 and C22) Fatty Acid Biosynthesis in Developing Seeds of Tropaeolum majus

    PubMed Central

    Pollard, Michael R.; Stumpf, Paul K.

    1980-01-01

    The storage triacylglycerols of nasturtium (Tropaeolum majus) seeds are composed principally of cis-11-eicosenoate and cis-13-docosenoate. To investigate the biosynthesis of these C20 and C22 fatty acids, developing seed tissue was incubated with various 14C-labeled precursors. Incubation with [1-14C]acetate produced primarily cis-11-[1-14C]eicosenoate and cis-13-[1,3-14C]docosenoate in the triacylglycerol fraction, the odd-carbon [U-14C]oleate also formed from [14C] acetate was in the polar lipid fraction. Kinetic data showed that this oleate was not channeled into cis-11-eicosenoate nor cis-13-docosenoate over a 24-hour period. Under suitable conditions, nasturtium seed could also produce [14C]stearate, [14C]eicosenoate, and [14C]docosenoate from [1-14C]acetate. The results are discussed in terms of the number of pathways producing fatty acids. From pool size and other considerations, the results can be rationalized only in terms of different de novo systems for oleate biosythesis, one supplying oleate for incorporation into phospholipids and the other supplying oleate for chain elongation and subsequent esterification into triacylglycerols. Because of the probable heterogeneous nature of the seed tissue, it is not known if these two systems are operating in different cell types, in the same cell type at different stages of development, or in the same cell type concurrently. PMID:16661495

  14. Effect of blends of dehydrated green pea flour and amaranth seed flour on the rheological, microstructure and pasta making quality.

    PubMed

    Sudha, M L; Leelavathi, K

    2012-12-01

    Effect of dehydrated green pea flour (DGPF) and additives like glycerol mono stearate (GMS), sodium stearoyl lactylate (SSL) and dry gluten on the rheological characteristics and pasta making quality made from Indian Triticum aestivum was studied. 5-10% of amaranth seed flour was used in the formulation to enhance the protein and fiber contents of the product. Increase in DGPF from 0 to 30% decreased the maximum consistency values from 550 to 513 FU, whereas the mixing tolerance index values decreased from 108 to 52 FU. The cooked weight and cooking loss increased from 320.8 to 332.9 g% and 5.0 to 8.2% respectively and the firmness values decreased from 104 to 75 g. Sensory evaluation of pasta showed that addition of DGPF above 20% resulted in greenish colour pasta of mashy texture. Addition of additives improved the quality of pasta at 30% level as seen in the reduction in the cooking loss from 8.2 to 5.9%, increase in the firmness values to 140 g and improvement in the eating quality. Protein content of pasta improved from 9.56 to 16.57%. Scanning electron microscopic studies revealed that the addition of additives in combination helped in the formation of rupture free structure with a continuous network. PMID:24293690

  15. End point determination of blending process for trimebutine tablets using principle component analysis (PCA) and partial least squares (PLS) regression.

    PubMed

    Lee, Sun-Hee; Lee, Jun-Ho; Cho, Soohwa; Do, Sung-Ho; Woo, Young-Ah

    2012-09-01

    This study showed near Infrared (NIR) and Raman spectroscopy with a multivariate calibration approach were very effective to determine blend uniformity end-point. A set of 36 trimebutine samples containing magnesium stearate, stearic acid, colloidal silicon oxide, talc as excipients (0.9%∼1.8%) was acquired from six positions during blending processing with U-type blender from 0 to 30 min. Principle component analysis (PCA) with NIR and Raman spectral data was used to confirm the end-point of blending. After 30 min, the scores of principle component (PC) 1 and principle component (PC) 2 for samples moved into one point, which clearly indicated the mixture of sample became homogenous. In addition, NIR and Raman spectroscopy has been applied to the quantitative analysis of 20 trimebutine samples containing 2∼40% in mixture granules, which divided into a calibration set of 15 samples and a prediction set of 5 samples for NIR spectral data. The standard error of calibration (SEC) and standard error of prediction (SEP) are 0.15% and 0.13%, respectively using NIR while SEC and SEP of 0.95% and 0.91% are obtained using Raman spectroscopy. The results showed the NIR and Raman spectroscopy with a multivariate calibration such as PCA and PLS provide the possibility of real time monitoring of homogeneity and content uniformity during blending process. PMID:23054717

  16. Cu-Fe-S Nanocrystals Exhibiting Tunable Localized Surface Plasmon Resonance in the Visible to NIR Spectral Ranges.

    PubMed

    Gabka, Grzegorz; Bujak, Piotr; Ostrowski, Andrzej; Tomaszewski, Waldemar; Lisowski, Wojciech; Sobczak, Janusz W; Pron, Adam

    2016-07-01

    Cu-Fe-S nanocrystals exhibiting a strong localized surface plasmon resonance (LSPR) effect were synthesized for the first time. The elaborated reproducible preparation procedure involved copper(II) oleate, iron(III) stearate, and sulfur powder dissolved in oleylamine (OLA) as precursors. The wavelength of the plasmonic resonance maximum could be tuned by changing the Cu/Fe ratio in the resulting nanocrystals, being the most energetic for the 1:1 ratio (486 nm) and undergoing a bathochromic shift to ca. 1200 nm with an increase to 6:1. LSPR could also be observed in nanocrystals prepared from the same metal precursors and sulfur powder dissolved in 1-octadecene (ODE), provided that the sulfur precursor was taken in excess. Detailed analysis of the reaction mixture by chromatographic techniques, supplemented by mass spectrometry and (1)H NMR spectroscopy enabled the identification of the true chemical nature of the sulfur precursor in S/OLA, namely, (C18H35NH3(+))(C18H35NH-S8(-)), a reactive product of the reduction of elemental sulfur by the amine groups of OLA. In the case of the S/ODE precursor, the true precursors are much less reactive primary or secondary thioethers and dialkyl polysulfides. PMID:27300320

  17. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

    PubMed Central

    Andalib, Sare; Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat

    2012-01-01

    Background: Nanostructured lipid carriers (NLC) are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol), lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of –25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers. PMID:23326776

  18. Novel sustained release and swellable gastroretentive dosage form for ciprofloxacin hydrochloride

    PubMed Central

    Gaikwad, Vinay Dhananjay; Yadav, Vishal Dadasaheb; Gaikwad, Manish Dhananjay

    2014-01-01

    Introduction: The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form. Materials and Methods: Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant. Results: The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits. Conclusion: The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants. PMID:25006553

  19. IMPROVED BONDING METHOD

    DOEpatents

    Padgett, E.V. Jr.; Warf, D.H.

    1964-04-28

    An improved process of bonding aluminum to aluminum without fusion by ultrasonic vibrations plus pressure is described. The surfaces to be bonded are coated with an aqueous solution of alkali metal stearate prior to assembling for bonding. (AEC) O H19504 Present information is reviewed on steady state proliferation, differentiation, and maturation of blood cells in mammals. Data are cited from metabolic tracer studies, autoradiographic studies, cytologic studies, studies of hematopoietic response to radiation injuries, and computer analyses of blood cell production. A 3-step model for erythropoiesis and a model for granulocyte kinetics are presented. New approaches to the study of lymphocytopoiesis described include extracorporeal blood irradiation to deplete lymphocytic tissue without direct injury to the formative tissues as a means to study the stressed system, function control, and rates of proliferation. It is pointed out that present knowledge indicates that lymphocytes comprise a mixed family, with diverse life spans, functions, and migration patterns with apparent aimless recycling from modes to lymph to blood to nodes that has not yet been quantitated. Areas of future research are postulated. (70 references.) (C.H.)

  20. A Tiered Analytical Approach for Investigating Poor Quality Emergency Contraceptives

    PubMed Central

    Monge, María Eugenia; Dwivedi, Prabha; Zhou, Manshui; Payne, Michael; Harris, Chris; House, Blaine; Juggins, Yvonne; Cizmarik, Peter; Newton, Paul N.; Fernández, Facundo M.; Jenkins, David

    2014-01-01

    Reproductive health has been deleteriously affected by poor quality medicines. Emergency contraceptive pills (ECPs) are an important birth control method that women can use after unprotected coitus for reducing the risk of pregnancy. In response to the detection of poor quality ECPs commercially available in the Peruvian market we developed a tiered multi-platform analytical strategy. In a survey to assess ECP medicine quality in Peru, 7 out of 25 different batches showed inadequate release of levonorgestrel by dissolution testing or improper amounts of active ingredient. One batch was found to contain a wrong active ingredient, with no detectable levonorgestrel. By combining ultrahigh performance liquid chromatography-ion mobility spectrometry-mass spectrometry (UHPLC-IMS-MS) and direct analysis in real time MS (DART-MS) the unknown compound was identified as the antibiotic sulfamethoxazole. Quantitation by UHPLC-triple quadrupole tandem MS (QqQ-MS/MS) indicated that the wrong ingredient was present in the ECP sample at levels which could have significant physiological effects. Further chemical characterization of the poor quality ECP samples included the identification of the excipients by 2D Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY 1H NMR) indicating the presence of lactose and magnesium stearate. PMID:24748219

  1. Attempts to find phenotypic markers of the virulence plasmid of Rhodococcus equi.

    PubMed Central

    De La Peña-Moctezuma, A; Prescott, J F; Goodfellow, M

    1996-01-01

    Four isolates of Rhodococcus equi, from pneumonic foals, and containing the 85 kb virulence plasmid, a porcine isolate containing an 80 kb plasmid, and their plasmid cured derivatives, were examined for 239 phenotypic properties in an attempt to find characters other than the virulence-associated protein (VapA) which might be encoded by the virulence plasmid in organisms grown at 37 degrees C. Tests chosen included those which have previously given variable results for R. equi isolates, since such variability might be attributed to plasmid curing, and characteristics which have been described as properties of plasmids of Rhodococcus species other than R. equi. Tests included cadmium resistance, Congo red binding, resistance to 26 antibiotics, conventional clinical microbiological tests, utilization of 95 different carbon sources, enzymatic activities in API ZYM, fluorogenic assays for exo- and endopeptidase, glycosidase activities, and testosterone degradation. Apart from production of VapA by foal isolates, no phenotypic property was identified in the plasmid-positive isolates. Phenotypic characteristics of R. equi that have not been described before, and might be useful in identification were: metabolism of N-acetyl-beta D-glucopyranoside, alpha- and beta-hydroxybutyric, alpha-ketobutyric and N-acetyl-glutamic acids, of methylpyruvate, heptanoate, nonanoate and stearate esters; exopeptidase activity against alanine-alanine-tyrosine, alanine-phenylalanine-lysine, glycine-arginine, lysine-alanine, and valine-glycine-alanine; endopeptidase activity against arginine and methionine; and hydrolysis of bis-phosphate ester. PMID:8825990

  2. Shape-Memory Polymers Based on Fatty Acid-Filled Elastomeric Ionomers

    NASA Astrophysics Data System (ADS)

    Izzo, Elise; Weiss, Robert

    2009-03-01

    Shape memory polymers (SMPs) have applications as medical devices, actuators, sensors, artificial muscles, switches, smart textiles, and self-deployable structures. All previous design of SMPs has involved synthesizing new polymers or modifying existing polymers. This paper describes a new type of SMP based on blends of an elastomeric ionomer and low molar mass fatty acids or their salts (FAS). Shape memory elastomers were prepared from mixtures of a sulfonated EPDM ionomer and various amounts of a FAS (e.g., zinc stearate, zinc oleate, and various aliphalic acids). Nanophase separation of the metal sulfonate groups provided the ``permanent'' crosslinks, while sub-microscopic crystals of the low molecular weight FAS provided a physical crosslink needed for the temporary shape. The material was deformed above the melting point of the FAS and the new shape was fixed by cooling the material while under stress to below the melting point of the FAS. Polar interactions between the ionomer and the FAS stabilized the dispersion of the FAS in the polymer and provided the continuity between the phases that allowed the crystals of the FAS to provide a second network of physical crosslinks. The temporary shape was erased and the material returned to the primary shape by heating above the melting point of the FAS.

  3. Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori.

    PubMed

    Abou Youssef, Nancy Abdel Hamid; Kassem, Abeer Ahmed; El-Massik, Magda Abd Elsamea; Boraie, Nabila Ahmed

    2015-01-01

    The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol(®) and Compritol(®) were incorporated into G-based formulations (G1%C1%). Mz:lipid ratio was 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing. Alg4%C2% FRS exhibited short gelation lag time (3s), long duration (>24h), floating lag time 1m in and duration >24h, and a reliable sustained drug release (MDT 6h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz:GMS 1:1) enhanced the gelation lag time and duration (6s and >24h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori. PMID:25843757

  4. Controlled-release triple anti-inflammatory therapy based on novel gastroretentive sponges: characterization and magnetic resonance imaging in healthy volunteers.

    PubMed

    Tadros, Mina Ibrahim; Fahmy, Rania Hassan

    2014-09-10

    The current work aimed to develop novel composite sponges of chitosan (CH)-chondroitin sulfate (CS) as a low-density gastroretentive delivery system for lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are expected to expand and float upon contact with gastric fluids for prolonged times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios, lyophilized, coated with magnesium stearate and compressed. The CH:CS interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed-sponges were evaluated for appearance, structure, porosity, pore diameter, density, wetting-time, floating characteristics, adhesion-retention, and LOR-release. The gastroretentivity of the best achieved magnetite-loaded sponges was monitored in healthy volunteers via MRI. The interaction between CH (protonated amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation. DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed interconnecting porous-network structures. The porosity, mean pore diameter, and bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4 nm, and 0.670 g/mL, respectively. They showed complete wetting within seconds, gradual size-expansion within minutes and prolonged adhesion for hours. Controlled LOR-release profiles were tailored over 12h to satisfy individual patient needs. Monitoring of sponges via MRI proved their gastroretentivity for at least 5h. PMID:24928130

  5. Optimization of poorly compactable drug tablets manufactured by direct compression using the mixture experimental design.

    PubMed

    Martinello, Tiago; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Taqueda, Maria Elena Santos; Consiglieri, Vladi O

    2006-09-28

    The poor flowability and bad compressibility characteristics of paracetamol are well known. As a result, the production of paracetamol tablets is almost exclusively by wet granulation, a disadvantageous method when compared to direct compression. The development of a new tablet formulation is still based on a large number of experiments and often relies merely on the experience of the analyst. The purpose of this study was to apply experimental design methodology (DOE) to the development and optimization of tablet formulations containing high amounts of paracetamol (more than 70%) and manufactured by direct compression. Nineteen formulations, screened by DOE methodology, were produced with different proportions of Microcel 102, Kollydon VA 64, Flowlac, Kollydon CL 30, PEG 4000, Aerosil, and magnesium stearate. Tablet properties, except friability, were in accordance with the USP 28th ed. requirements. These results were used to generate plots for optimization, mainly for friability. The physical-chemical data found from the optimized formulation were very close to those from the regression analysis, demonstrating that the mixture project is a great tool for the research and development of new formulations. PMID:16806756

  6. Analytical procedure for quantifying five compounds suspected as possible contaminants in recycled paper/paperboard for food packaging.

    PubMed

    Song, Y S; Park, H J; Komolprasert, V

    2000-12-01

    Because contaminants in recycled paper intended for food packaging could be a risk to public health, analytical methods are needed to identify and quantify residues of concern in paper/paperboard. The U. S. Food and Drug Administration is considering development of a guidance document for testing levels of contaminants that might be retained through paper recycling processes. An analytical procedure was developed using paper spiked with suspected contaminants at concentrations of 1-50 ppm in the paper. Benzophenone, dimethyl phthalate, anthracene, methyl stearate, and pentachlorophenol were introduced by soaking the paper in a solution in acetone at 25 degrees C for 24 h; the paper was removed and dried by evaporating the solvent with nitrogen. The model contaminant residues were extracted from the paper using ultrasonication and quantified by GC with flame ionization and electron capture detectors. Recoveries from the spiked paper were 80-109% with a repeatability of +/-4%. The method was also used to analyze commercial recycled paperboard to validate its applicability. PMID:11141258

  7. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol.

    PubMed

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-01-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs. PMID:21711808

  8. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    NASA Astrophysics Data System (ADS)

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-12-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  9. Pore blocking: An innovative formulation strategy for the design of alcohol resistant multi-particulate dosage forms.

    PubMed

    Schrank, Simone; Jedinger, Nicole; Wu, Shengqian; Piller, Michael; Roblegg, Eva

    2016-07-25

    In this work calcium stearate (CaSt) multi-particulates loaded with codeine phosphate (COP) were developed in an attempt to provide extended release (ER) combined with alcohol dose dumping (ADD) resistance. The pellets were prepared via wet/extrusion spheronization and ER characteristics were obtained after fluid bed drying at 30°C. Pore blockers (i.e., xanthan, guar gum and TiO2) were integrated to control the uptake of ethanolic media, the CaSt swelling and consequently, the COP release. While all three pore blockers are insoluble in ethanol, xanthan dissolves, guar gum swells and TiO2 does not interact with water. The incorporation of 10 and 15% TiO2 still provided ER characteristics and yielded ADD resistance in up to 40v% ethanol. The in-vitro data were subjected to PK simulations, which revealed similar codeine plasma levels when the medication is used concomitantly with alcoholic beverages. Taken together the in-vitro and in-silico results demonstrate that the incorporation of appropriate pore blockers presents a promising strategy to provide ADD resistance of multi-particulate systems. PMID:27282540

  10. Development of Organogel-Derived Capsaicin Nanoemulsion with Improved Bioaccessibility and Reduced Gastric Mucosa Irritation.

    PubMed

    Lu, Muwen; Cao, Yong; Ho, Chi-Tang; Huang, Qingrong

    2016-06-15

    Capsaicin (CAP) is the major active component in chili peppers with health-promoting benefits. However, the low bioavailability and irritating quality of CAP greatly limit its applications in functional foods. The objective of this study was to develop a food-grade nanoemulsion to increase the dissolution and bioaccessibility of CAP and to alleviate its irritating effects. To achieve this goal, CAP was first dissolved in medium-chain triacylglycerol (MCT), followed by the addition of sucrose stearate S-370 as organogelator to develop CAP-loaded organogel. The oil-in-water (O/W) emulsion was formed using organogel as the oil phase and Tween 80 as the emulsifier. After ultrasonication treatment, droplet sizes of emulsion were decreased to 168 nm with enhanced dissolution rate and bioaccessibility. In vivo study further confirmed the reduced rat gastric mucosa irritation caused by CAP. The organogel-derived nanoemulsion was proved to be an effective delivery system for CAP-based functional food products. PMID:27170269

  11. Integration of Metabolomics and Transcriptomics Revealed a Fatty Acid Network Exerting Growth Inhibitory Effects in Human Pancreatic Cancer

    PubMed Central

    Zhang, Geng; He, Peijun; Tan, Hanson; Budhu, Anuradha; Gaedcke, Jochen; Ghadimi, B. Michael; Ried, Thomas; Yfantis, Harris G.; Lee, Dong H.; Maitra, Anirban; Hanna, Nader; Alexander, H. Richard; Hussain, S. Perwez

    2013-01-01

    Purpose To identify metabolic pathways that are perturbed in pancreatic ductal adenocarcinoma (PDAC), we investigated gene-metabolite networks with integration of metabolomics and transcriptomics. Experimental design We have performed global metabolite profiling analysis on two independent cohorts of resected PDAC cases to identify critical metabolites alteration that may contribute to the progression of pancreatic cancer. We then searched for gene surrogates that were significantly correlated with the key metabolites by integrating metabolite and gene expression profiles. Results 55 metabolites were consistently altered in tumors as compared with adjacent nontumor tissues in a test cohort (N=33) and an independent validation cohort (N=31). Weighted network analysis revealed a unique set of free fatty acids (FFAs) that were highly co-regulated and decreased in PDAC. Pathway analysis of 157 differentially expressed gene surrogates revealed a significantly altered lipid metabolism network, including key lipolytic enzymes PNLIP, CLPS, PNLIPRP1, and PNLIPRP2. Gene expressions of these lipases were significantly decreased in pancreatic tumors as compared with nontumor tissues, leading to reduced FFAs. More importantly, a lower gene expression of PNLIP in tumors was associated with poorer survival in two independent cohorts. We further demonstrated that two saturated FFAs, palmitate and stearate significantly induced TRAIL expression, triggered apoptosis, and inhibited proliferation in pancreatic cancer cells. Conclusions Our results suggest that impairment in a lipolytic pathway involving lipases and a unique set of FFAs, may play an important role in the development and progression of pancreatic cancer and provide potential targets for therapeutic intervention. PMID:23918603

  12. Effect of Rare Earth Ions on the Properties of Composites Composed of Ethylene Vinyl Acetate Copolymer and Layered Double Hydroxides

    PubMed Central

    Wang, Lili; Li, Bin; Zhao, Xiaohong; Chen, Chunxia; Cao, Jingjing

    2012-01-01

    Background The study on the rare earth (RE)-doped layered double hydroxides (LDHs) has received considerable attention due to their potential applications in catalysts. However, the use of RE-doped LDHs as polymer halogen-free flame retardants was seldom investigated. Furthermore, the effect of rare earth elements on the hydrophobicity of LDHs materials and the compatibility of LDHs/polymer composite has seldom been reported. Methodology/Principal Findings The stearate sodium surface modified Ni-containing LDHs and RE-doped Ni-containing LDHs were rapidly synthesized by a coprecipitation method coupled with the microwave hydrothermal treatment. The influences of trace amounts of rare earth ions La, Ce and Nd on the amount of water molecules, the crystallinity, the morphology, the hydrophobicity of modified Ni-containing LDHs and the adsorption of modifier in the surface of LDHs were investigated by TGA, XRD, TEM, contact angle and IR, respectively. Moreover, the effects of the rare earth ions on the interfacial compatibility, the flame retardancy and the mechanical properties of ethylene vinyl acetate copolymer (EVA)/LDHs composites were also explored in detail. Conclusions/Significance S-Ni0.1MgAl-La displayed more uniform dispersion and better interfacial compatibility in EVA matrix compared with other LDHs. Furthermore, the S-Ni0.1MgAl-La/EVA composite showed the best fire retardancy and mechanical properties in all composites. PMID:22693627

  13. Acute and chronic Legionnaires' disease and co-existent tuberculosis: a trial of erythromycin.

    PubMed

    Hamedani, P; Hafeez, S; Ali, J; Memon, R; Ali, S; Ali, M; Ansari, M; Raza, R

    1989-01-01

    To assess the prevalence of Legionnaires' disease, 115 patients with 'difficult-to-treat' chest infections were screened for Legionnella pneumophila. The results were positive in 10 (37%) of 27 patients with pulmonary tuberculosis, 15 (22%) of 68 with a recent onset acute respiratory infection, and 7 (35%) of 20 patients with history of a chronic respiratory infection. These 32 patients were enrolled in an open therapeutic trial of erythromycin. Less severe cases (17 of 32) received erythromycin stearate orally (500 mg 4-times daily) for up to 28 days, while severe cases were treated for the first few days with intravenous erythromycin lactobionate (4 g/day). Weekly chest X-ray examinations revealed prompt resolution. Most patients had no signs and symptoms detectable after 7 days, and none persisted up to 28 days. There were no therapeutic failures and microbiological tests on Day 28 were negative for Legionella pneumophila. It is suggested that the possibility of co-existing legionellosis should be considered in all patients with difficult to treat acute and chronic chest infections, particularly in developing countries where tuberculosis is very common, and treatment instituted or supplemented with erythromycin as the drug of choice. PMID:2680287

  14. Application of waste bulk moulded composite (BMC) as a filler for isotactic polypropylene composites

    PubMed Central

    Barczewski, Mateusz; Matykiewicz, Danuta; Andrzejewski, Jacek; Skórczewska, Katarzyna

    2016-01-01

    The aim of this study was to produce isotactic polypropylene based composites filled with waste thermosetting bulk moulded composite (BMC). The influence of BMC waste addition (5, 10, 20 wt%) on composites structure and properties was investigated. Moreover, additional studies of chemical treatment of the filler were prepared. Modification of BMC waste by calcium stearate (CaSt) powder allows to assess the possibility of the production of composites with better dispersion of the filler and more uniform properties. The mechanical, processing, and thermal properties, as well as structural investigations were examined by means of static tensile test, Dynstat impact strength test, differential scanning calorimetry (DSC), wide angle X-ray scattering (WAXS), melt flow index (MFI) and scanning electron microscopy (SEM). Developed composites with different amounts of non-reactive filler exhibited satisfactory thermal and mechanical properties. Moreover, application of the low cost modifier (CaSt) allows to obtain composites with better dispersion of the filler and improved processability. PMID:27222742

  15. Photochemical properties and shape evolution of CdSe QDs in a non-injection reaction

    NASA Astrophysics Data System (ADS)

    Park, Eunjung; Ryu, Jiyoung; Choi, Youngseon; Hwang, Kwang-Jin; Song, Rita

    2013-04-01

    Highly monodispersed CdSe quantum dots (QDs) were prepared without an injection procedure. A series of Cd salts of long chain fatty acids, including Cd-myristate (C14), Cd-palmitate (C16) and Cd-stearate (C18) was prepared, and all metallic precursors and surfactants were mixed together followed by increasing the temperature in a controlled manner. The reaction resulted in highly monodisperse and bright zinc blende QDs. In addition, the effects of specific ligands which have been known to lead anisotropic growth of the nanocrystals in the injection method were investigated. The use of alkyl phosphonic acid and alkyl amine was found to produce extremely monodisperse CdSe QDs with a high quantum yield. This procedure was proven to be able to yield a large quantity of zinc blende CdSe QDs (2 g) in a one-pot reaction. The use of a controlled amount of tetradecylphosphonic acid and octadecylamine resulted in tetrapod- and match-shaped QDs, the first reported by a non-injection method. These results clearly demonstrate that appropriate combination of precursors can provide high quality of CdSe nanocrystals in terms of quantum yield, monodispersity and shape control by a non-injection method.

  16. A novel alkaline keratinase from Bacillus subtilis DP1 with potential utility in cosmetic formulation.

    PubMed

    Sanghvi, Gaurav; Patel, Harshit; Vaishnav, Devendra; Oza, Tejas; Dave, Gaurav; Kunjadia, Prashant; Sheth, Navin

    2016-06-01

    The Bacillus subtilis DP1 was isolated from poultry farm soil at Anand district, India. The highest enzyme production (379.65U/ml) was obtained at pH 10.0, a temperature of 37°C and a growth period of 72h. The extracellular keratinase was purified by gel filtration chromatography with 27.98 purification fold. Purity was also confirmed by High-Performance Liquid Chromatography (HPLC) analysis, where a major peak having retention time of 2.5min was obtained on C18 column using photo diode array detector. Purified keratinase was stable in a broad range of pH (8-12) and temperature (20-50°C) with optimum at pH 10.0 and 37°C. The metallic ions, Ca(2+) and Mg(2+) enhance keratinase activity. Secondary structure from Circular Dichroism (CD) spectra implies that purified keratinase is largely β-pleated sheet rich protein. For preparation of dehairing cream formulation, compatibility studies of excipients were carried out. Fourier transform infrared spectroscopy (FTIR) spectra of sodium stearate, calcium carbonate and sodium lauryl sulphate shows no reactivity of functional groups and hence mixture was compatible for formulation of keratinase dehairing cream. Prepared biological depilatory was able to remove hair more efficiently compared to marketed formulations. PMID:26940376

  17. Heparin modification enhances the delivery and tumor targeting of paclitaxel-loaded N-octyl-N-trimethyl chitosan micelles.

    PubMed

    Zhang, Feiran; Fei, Jia; Sun, Minjie; Ping, Qineng

    2016-09-10

    Polycations have been widely used as efficient drug and gene carriers. However, the further application of polycation nanocarriers is greatly hampered by the serious cytotoxicity caused by exposed positive charges. Despite recent progress towards the therapeutic delivery of nucleic acids, there remains a compelling need for development of novel delivery systems for various types of drug. Here, we created mixed micelles based on N-octyl-N-trimethyl chitosan (OTMC) and coated them with an anionic polymer for delivery of paclitaxel (PTX). OTMC/PEG-100 stearate (S-100) micelles (PTX-SN) were firstly prepared by a dialysis method with a high drug loading efficiency and positive charge. PTX-SN micelles were then coated with two anionic polymers, heparin sodium (PTX-HSN) and sodium carboxymethyl cellulose (PTX-CSN) to shield positive charges. Both PTX-HSN and PTX-CSN micelles showed decreased cytotoxicity and hemolysis while retaining high uptake efficiency. PTX-HSN micelles were taken up more effectively than PTX-CSN by HeLa cells, which over-express heparanase. PTX-HSN micelles persisted longer in the circulation of rats than free drug in pharmacokinetic studies. DIR-HSN micelles accumulated strongly in tumors, and PTX-HSN micelles significantly inhibited tumor growth in tumor-bearing mice. Overall, the results validate heparin-coated OTMC micelles as safe and effective tumor-targeting carriers that are suitable for anti-tumor drug delivery. PMID:27426109

  18. Evidence of female sex pheromones and characterization of the cuticular lipids of unfed, adult male versus female blacklegged ticks, Ixodes scapularis.

    PubMed

    Carr, Ann L; Sonenshine, Daniel E; Strider, John B; Roe, R Michael

    2016-04-01

    Copulation in Ixodes scapularis involves physical contact between the male and female (on or off the host), male mounting of the female, insertion/maintenance of the male chelicerae in the female genital pore (initiates spermatophore production), and the transfer of the spermatophore by the male into the female genital pore. Bioassays determined that male mounting behavior/chelicerae insertion required direct contact with the female likely requiring non-volatile chemical cues with no evidence of a female volatile sex pheromone to attract males. Unfed virgin adult females and replete mated adult females elicited the highest rates of male chelicerae insertion with part fed virgin adult females exhibiting a much lower response. Whole body surface hexane extracts of unfed virgin adult females and males, separately analyzed by GC-MS, identified a number of novel tick surface associated compounds: fatty alcohols (1-hexadecanol and 1-heptanol), a fatty amide (erucylamid), aromatic hydrocarbons, a short chain alkene (1-heptene), and a carboxylic acid ester (5β-androstane). These compounds are discussed in terms of their potential role in female-male communication. The two most abundant fatty acid esters found were butyl palmitate and butyl stearate present in ratios that were sex specific. Only 6 n-saturated hydrocarbons were identified in I. scapularis ranging from 10 to 18 carbons. PMID:26864785

  19. Studies of drag on the nanocomposite superhydrophobic surfaces

    NASA Astrophysics Data System (ADS)

    Brassard, Jean-Denis; Sarkar, D. K.; Perron, Jean

    2015-01-01

    The nanocomposite thin films of stearic acid (SA)-functionalized ZnO nanoparticles incorporated in epoxy polymer matrix have been achieved. The X-ray diffraction (XRD) studies show the formation of zinc stearate on ZnO nanoparticles as the confirmation of SA-functionalization of ZnO nanoparticles in the thin films. Morphological analyses reveal the presence of micro-holes with the presence of irregular nanoparticles. The measured root mean square (rms) roughness of the thin film is found to be 12 ± 1 μm with the adhesion of 5B on both glass and aluminum substrates. The wetting property shows that the surface of the film is superhydrophobic with the contact angle of water of 156 ± 4° having contact angle hysteresis (CAH) of 4 ± 2°. The average terminal velocity in the water of the as-received glass spheres and superhydrophobic spheres were found to be 0.66 ± 0.01 m/s and 0.72 ± 0.01 m/s respectively. Consequently, the calculated average coefficients of the surface drag of the as-received glass sphere and superhydrophobic glass sphere were 2.30 ± 0.01 and 1.93 ± 0.03, respectively. Hence, the drag reduction on the surface of superhydrophobic glass sphere is found to be approximately 16% lower than as-received glass sphere.

  20. Reductive metabolism of carbon tetrachloride by human cytochromes P-450 reconstituted in phospholipid vesicles: mass spectral identification of trichloromethyl radical bound to dioleoyl phosphatidylcholine.

    PubMed Central

    Trudell, J R; Bösterling, B; Trevor, A J

    1982-01-01

    It has been proposed that covalent binding of reactive metabolites to liver membrane constituents may be responsible for the hepatoxicity of carbon tetrachloride. This study demonstrates that trichloromethyl free radical is the major reductive metabolite of carbon tetrachloride by cytochrome P-450 and that this free radical is capable of binding to double bonds of fatty acyl chains of the phospholipids in the membrane surrounding cytochrome P-450. The structural identification of the reactive free radical metabolite and the product of its addition to phospholipids was accomplished by use of a reconstituted system of human cytochromes P-450, NADPH-cytochrome P-450 reductase, and cytochrome b5 in phospholipid vesicles. The reconstituted vesicles contained a mixture of dioleoyl phosphatidylcholine and egg phosphatidylethanolamine that served as both structural components and targets for trichloromethyl free radical binding. After incubation of these vesicles under a N2 atmosphere in the presence of NADPH with 14CCl4, the phospholipids were extracted and then separated by high-pressure liquid chromatography. The dioleoyl phosphatidylcholine fraction was transesterified and the resulting single 14C-labeled fatty acid methyl ester was purified by reverse-phase chromatography. Desorption chemical ionization mass spectrometry with ammonia as reagent gas as well as desorption electron-impact mass spectrometry permitted identification of the molecular structure as a mixture of 9- and 10-(trichloromethyl)stearate methyl esters. PMID:6953422

  1. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

    NASA Astrophysics Data System (ADS)

    Niculae, G.; Lacatusu, I.; Badea, N.; Meghea, A.

    2012-08-01

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.

  2. Combination of an enzymatic method and HPLC for the quantitation of cholesterol in cultured cells.

    PubMed

    Contreras, J A; Castro, M; Bocos, C; Herrera, E; Lasunción, M A

    1992-06-01

    The study of the cellular events that lead to the foam cell formation requires the development of fast, accurate, and sensitive methods to quantify cholesterol in cultured cells. Here we describe a procedure that allows the rapid determination of free and total cholesterol in a reduced number of cells, which makes it very suitable for cholesterol determination in cell cultures. The method consists of the enzymatic conversion of cholesterol to cholest-4-ene-3-one by cholesterol oxidase followed by the analysis of the sample by high performance liquid chromatography (HPLC) to detect this oxidized product. Due to the relatively high wavelength at which cholest-4-ene-3-one has its maximum absorption (240 nm), other cellular components do not interfere with the chromatographic procedure and prior lipid extraction is not required. Moreover, the duration of each chromatogram is about 3 min, contributing to the celerity of the method. All the cholesteryl esters used (oleate, palmitate, stearate and linoleate) were quantitatively hydrolyzed by incubation with cholesterol esterase; this was observed to occur with both pure standards and in cell homogenates. Sensitivity is enough to allow the determination of free and total cholesterol in less than 5 x 10(3) cells. We have applied this method to human monocyte-derived macrophages and the values obtained for free and total cholesterol are in close agreement with published data. PMID:1512516

  3. A study of the properties of compacts from silicified microcrystalline celluloses.

    PubMed

    Muzíková, Jitka; Nováková, Petra

    2007-07-01

    The paper deals with a study of tensile strength and disintegration time of compacts made from silicified microcrystalline celluloses, Prosolv SMCC 90, and Prosolv HD 90, in dependence on compression force, addition of two types of lubricants, and two active ingredients. The lubricants were magnesium stearate and sodium stearyl fumarate in a concentration of 0.5%, the active ingredients being ascorbic acid and acetylsalicylic acid in a concentration of 50%. Prosolv SMCC 90 proved to be better compatible than Prosolv HD 90; the compacts were of higher strength, which was markedly increased with increasing compression force. Prosolv HD 90 was more sensitive to additions of lubricants, and a greater decrease in strength was recorded due to the influence of sodium stearyl fumarate. The effect of lubricants on the strength of compacts in the presence of active ingredients was not identical. The disintegration time of compacts from Prosolv HD 90 without as well as with lubricants was shorter than from Prosolv SMCC 90 and was increasing with increasing compression force. Disintegration time was increased with added lubricants, and it was markedly shortened by addition of active ingredients. Compacts containing ascorbic acid possessed a shorter disintegration time than those containing acetylsalicylic acid, and it was not markedly influenced by the presence of lubricants. PMID:17654026

  4. Comparative evaluation of silicified microcrystalline cellulose II as a direct compression vehicle.

    PubMed

    Rojas, John; Kumar, Vijay

    2011-09-15

    The powder flow and tableting properties of novel silicified microcrystalline cellulose II (SMCCII) were evaluated and compared with current silicified cellulosic I excipients such as ProSolv(®) SMCC50 and ProSolv(®) SMCC90. This excipient was prepared by coprocessing cellulose II and silicon dioxide (SiO(2)) at a 95:5 ratio by spray drying. The novel SMCCII yielded more benefits in terms of functionality as compared with the parent cellulose II material. SMCCII had higher bulk and tap densities, better powder packing ability, reduced porosity, increased surface area, and increased flowability. This silicified excipient had the highest brittleness behavior as given by the Heckel, Leuenberger and brittle fracture index analyses. The mechanical properties of SMCCII, such as toughness and Young's modulus were comparable to those of commercial products. SMCCII was the least sensitive material to magnesium stearate, and blending time or reprocessing did not affect its compactibility. It also provided for the fastest compact disintegration and release of griseofulvin. This new material has the potential for use as a direct compression excipient. PMID:21708237

  5. Quantitation of active pharmaceutical ingredients and excipients in powder blends using designed multivariate calibration models by near-infrared spectroscopy.

    PubMed

    Li, Weiyong; Worosila, Gregory D

    2005-05-13

    This research note demonstrates the simultaneous quantitation of a pharmaceutical active ingredient and three excipients in a simulated powder blend containing acetaminophen, Prosolv and Crospovidone. An experimental design approach was used in generating a 5-level (%, w/w) calibration sample set that included 125 samples. The samples were prepared by weighing suitable amount of powders into separate 20-mL scintillation vials and were mixed manually. Partial least squares (PLS) regression was used in calibration model development. The models generated accurate results for quantitation of Crospovidone (at 5%, w/w) and magnesium stearate (at 0.5%, w/w). Further testing of the models demonstrated that the 2-level models were as effective as the 5-level ones, which reduced the calibration sample number to 50. The models had a small bias for quantitation of acetaminophen (at 30%, w/w) and Prosolv (at 64.5%, w/w) in the blend. The implication of the bias is discussed. PMID:15848006

  6. Release kinetics of papaverine hydrochloride from tablets with different excipients.

    PubMed

    Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

    2014-09-01

    The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

  7. An HPLC-MS/MS method for the separation of α-retinyl esters from retinyl esters.

    PubMed

    Goetz, Hilary J; Kopec, Rachel E; Riedl, Ken M; Cooperstone, Jessica L; Narayanasamy, Sureshbabu; Curley, Robert W; Schwartz, Steven J

    2016-09-01

    Enzymatic cleavage of the nonsymmetric provitamin A carotenoid α-carotene results in one molecule of retinal (vitamin A), and one molecule of α-retinal, a biologically inactive analog of true vitamin A. Due to structural similarities, α-retinyl esters and vitamin A esters typically coelute, resulting in the overestimation of vitamin A originating from α-carotene. Herein, we present a set of tools to identify and separate α-retinol products from vitamin A. α-Retinyl palmitate (αRP) standard was synthesized from α-ionone following a Wittig-Horner approach. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method employing a C30 column was then developed to separate the species. Authentic standards of retinyl esters and the synthesized α-RP confirmed respective identities, while other α-retinyl esters (i.e. myristate, linoleate, oleate, and stearate) were evidenced by their pseudomolecular ions observed in electrospray ionization (ESI) mode, fragmentation, and elution order. For quantitation, an atmospheric pressure chemical ionization (APCI) source operated in positive ion mode was used, and retinol, the predominant in-source parent ion was selected and fragmented. The application of this method to a chylomicron-rich fraction of human plasma is demonstrated. This method can be used to better determine the quantity of vitamin A derived from foods containing α-carotene. PMID:27423669

  8. Naked-eye cadmium sensor: using chromoionophore arrays of Langmuir-Blodgett molecular assemblies.

    PubMed

    Prabhakaran, Deivasigamani; Yuehong, Ma; Nanjo, Hiroshi; Matsunaga, Hideyuki

    2007-06-01

    This study demonstrates the possibility of a reversible naked-eye detection method for submicromolar levels of cadmium(II) using the Langmuir-Blodgett (L-B) technique. Molecular assemblies of 4-n-dodecyl-6-(2-thiazolylazo)resorcinol are transferred on precleaned microscopic glass slides, to act as a sensing probe. Isotherm (pi-A) measurements were performed to ensure the films' structural rigidity and homogeneity during sensor fabrication. The sensor surface morphology was characterized using atomic force microscopy and scanning electron microscopy. The probe membrane exhibits visual color transition, forming a series of reddish-orange to pinkish-purple complexes with cadmium, over a wide concentration range (0.04-44.5 microM). Cadmium response kinetics and the changes in the sensors' intrinsic optical properties were monitored using absorption spectroscopy and further confirmed using X-ray photoelectron spectroscopy. A hybrid L-B film composite of poly(vinyl stearate) and poly(vinyl-N-octadecylcarbamate) were investigated for enhancing sensor performance. The sensor was tested for its practical approach to prove its cadmium selectivity and sensitivity amid common matrix constituents using synthetic mixtures and real water samples. Using the sensor strips, the respective lower limits of cadmium detection and quantification are 0.039 and 0.050 microM, as estimated from a normalized linear calibration plot. PMID:17447727

  9. Ultrasonic approach for viscoelastic and microstructure characterization of granular pharmaceutical tablets.

    PubMed

    Saeedi Vahdat, Armin; Krishna Prasad Vallabh, Chaitanya; Hancock, Bruno C; Cetinkaya, Cetin

    2013-09-15

    The mechanical properties of a solid dosage, defined by its granular micro-structure and geometry, play a key role in its dissolution profile and performance. An ultrasonic method for extracting the viscoelastic material properties and granular structure of drug tablet compacts is introduced and its utility is demonstrated for tablet compacts made of microcrystalline cellulose (MCC), lactose monohydrate, and sodium starch glycolate as well as magnesium stearate as lubricant. The approach is based on the effect of viscoelasticity and internal micro-structures on the frequency-dependent attenuation of an ultrasonic wave propagating in a granular medium. The models for viscoelastic (a two-parameter Zener model) and scattering attenuation (Rayleigh model) mechanisms are employed. The material parameters including viscoelastic and scattering parameters (average Young's modulus, stress and strain relaxation time constants, and the Rayleigh scattering material parameter) and grain size distribution with a known distribution profile are extracted by an optimization algorithm based on the least square method. The results also indicate good agreement between experimentally and computationally determined phase and group velocities in compacted samples. It is found that the effects of both attenuation mechanisms are present and the extracted grain size distribution parameters are in good agreement with the optically determined values. PMID:23820132

  10. Wetting characteristics and stability of Langmuir-Blodgett carboxylate monolayers at the surfaces of calcite and fluorite

    SciTech Connect

    Jang, W.H.; Drelich, J.; Miller, J.D.

    1995-09-01

    Although surface chemistry fundamentals of semisoluble minerals have been studied by many researchers, detailed understanding of these systems is still incomplete. In situ Fourier transform infrared internal reflection spectroscopy (FT-IR/IRS) techniques have recently been used to successfully describe the adsorption of carboxylates at semisoluble mineral surfaces. The wetting characteristics of these adsorbed films, however, require further consideration. In this regard, the hydrophobicity and stability of transferred Langmuir-Blodgett (LB) monolayers of fatty acids at fluorite and calcite surfaces have been studied by contact angle measurements with water and diiodomethane. Generally, it was found that the transferred LB monolayers of fatty acids at a calcite surface are unstable whereas such monolayers transferred onto a fluorite surface are stable, as revealed from advancing and receding contact angle measurements. These results are believed to be due to incomplete reaction of the fatty acid monolayer at the calcite surface. In addition it was found that a closely packed well-ordered stearate monolayer similar to that of a transferred LB monolayer can be formed at fluorite surfaces by spontaneous adsorption and self-assembly from aqueous solutions. 41 refs., 13 figs., 1 tab.

  11. Guanidinium based blend anion exchange membranes for direct methanol alkaline fuel cells (DMAFCs)

    NASA Astrophysics Data System (ADS)

    Sajjad, Syed D.; Liu, Dong; Wei, Zi; Sakri, Shambhavi; Shen, Yi; Hong, Yi; Liu, Fuqiang

    2015-12-01

    Guanidinium based blend anion exchange membranes (AEMs) for direct methanol alkaline fuel cells have been fabricated and studied. The guanidinium prepolymer is first synthesized through a simple polycondensation process with the ion exchange moieties incorporated directly into the polymer backbone, and then is used to make guanidinium - chitosan (Gu-Chi) blend membranes. Besides, a lipophilic guanidinium prepolymer, synthesized by means of a precipitation reaction between sodium stearate and guanidinium salt, is adopted to tune solubility and mechanical properties of the blend AEMs. Results show that both ionic conductivity and methanol permeability of the AEMs can be tuned by blend composition and chemistry of the guanidinium based prepolymer. The selectivity (ratio of ionic conductivity to methanol permeability) of the fabricated membranes is superior to that of commercial membranes. Under fuel cell tests using 3 M methanol, the open circuit voltage (OCV) value for the blend AEM with 72 wt% of the guanidinium polymer (0.69 V) is much higher than that of the commercial Tokuyama A201 (0.47 V) at room temperature, while the blend AEMs with 50 wt% guanidinium content still show comparable values. Overall, the developed membranes demonstrate superior performance and therefore pose great promise for direct methanol anion exchange fuel cell (DMAFC) applications.

  12. A slow release calcium delivery system for the study of reparative dentine formation.

    PubMed

    Hunter, A R; Kirk, E E; Robinson, D H; Kardos, T B

    1998-06-01

    Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow. PMID:9863419

  13. Biocatalytic potential of lipase from Staphylococcus sp. MS1 for transesterification of jatropha oil into fatty acid methyl esters.

    PubMed

    Sharma, Monika; Singh, Shelley Sardul; Maan, Pratibha; Sharma, Rohit

    2014-11-01

    An extracellular lipase producing isolate Staphylococcus sp. MS1 was optimized for lipase production and its biocatalytic potential was assessed. Medium with tributyrin (0.25 %) and without any exogenous inorganic nitrogen source was found to be optimum for lipase production from Staphylococcus sp. MS1. The optimum pH and temperature for lipase production were found to be pH 7 and 37 °C respectively, showing lipase activity of 37.91 U. It showed good lipase production at pH 6-8. The lipase was found to be stable in organic solvents like hexane and petroleum ether, showing 98 and 88 % residual activity respectively. The biotransformation using the concentrated enzyme in petroleum ether resulted in the synthesis of fatty acid methyl esters like methyl oleate, methyl palmitate and methyl stearate. Thus, the lipase under study has got the potential to bring about transesterification of oils into methyl esters which can be exploited for various biotechnological applications. PMID:25115850

  14. Solvent-free enzymatic production of high quality cetyl esters.

    PubMed

    Serrano-Arnaldos, Mar; Máximo-Martín, María Fuensanta; Montiel-Morte, María Claudia; Ortega-Requena, Salvadora; Gómez-Gómez, Elisa; Bastida-Rodríguez, Josefa

    2016-04-01

    A solvent-free biocatalytic process for the synthesis of high quality cetyl laurate, myristate, palmitate and stearate has been optimized. This enzymatic procedure follows the fundamental principles of the Green Chemistry and lead to sustainable products, which can be labeled as natural and conform to the principal requirements for its use in high value-added goods. The four esters selected are the main components of spermaceti, a mixture of waxes very appreciated in cosmetic and pharmacy because of its physical properties and emolliency, which was formerly extracted from the head of the sperm whales. In this paper, the influence of the amount of biocatalyst, the commercially available Novozym(®) 435, and the temperature were studied in an open-air batch reactor before carrying out the synthesis in a high performance vacuum reactor with dry nitrogen input to shift the equilibrium towards product formation. Under optimal conditions, conversion was higher than 98.5 %. The characterization of the enzymatic cetyl esters puts in evidence that these are ultra-pure compounds, which have similar properties to the ones obtained through the conventional industrial processes with the extra benefit of being environmentally friendly. PMID:26801670

  15. Fabrication and Characterization of ZnO Langmuir-Blodgett Film and Its Use in Metal-Insulator-Metal Tunnel Diode.

    PubMed

    Azad, Ibrahim; Ram, Manoj K; Goswami, D Yogi; Stefanakos, Elias

    2016-08-23

    Metal-insulator-metal tunnel diodes have great potential for use in infrared detection and energy harvesting applications. The quantum based tunneling mechanism of electrons in MIM (metal-insulator-metal) or MIIM (metal-insulator-insulator-metal) diodes can facilitate rectification at THz frequencies. In this study, the required nanometer thin insulating layer (I) in the MIM diode structure was fabricated using the Langmuir-Blodgett technique. The zinc stearate LB film was deposited on Au/Cr coated quartz, FTO, and silicon substrates, and then heat treated by varying the temperature from 100 to 550 °C to obtain nanometer thin ZnO layers. The thin films were characterized by XRD, AFM, FTIR, and cyclic voltammetry methods. The final MIM structure was fabricated by depositing chromium/nickel over the ZnO on Au/Cr film. The current voltage (I-V) characteristics of the diode showed that the conduction mechanism is electron tunneling through the thin insulating layer. The sensitivity of the diodes was as high as 32 V(-1). The diode resistance was ∼80 Ω (at a bias voltage of 0.78 V), and the rectification ratio at that bias point was about 12 (for a voltage swing of ±200 mV). The diode response exhibited significant nonlinearity and high asymmetry at the bias point, very desirable diode performance parameters for IR detection applications. PMID:27464073

  16. VIS-NIR spectroscopy as a process analytical technology for compositional characterization of film biopolymers and correlation with their mechanical properties.

    PubMed

    Barbin, Douglas Fernandes; Valous, Nektarios A; Dias, Adriana Passos; Camisa, Jaqueline; Hirooka, Elisa Yoko; Yamashita, Fabio

    2015-11-01

    There is an increasing interest in the use of polysaccharides and proteins for the production of biodegradable films. Visible and near-infrared (VIS-NIR) spectroscopy is a reliable analytical tool for objective analyses of biological sample attributes. The objective is to investigate the potential of VIS-NIR spectroscopy as a process analytical technology for compositional characterization of biodegradable materials and correlation to their mechanical properties. Biofilms were produced by single-screw extrusion with different combinations of polybutylene adipate-co-terephthalate, whole oat flour, glycerol, magnesium stearate, and citric acid. Spectral data were recorded in the range of 400-2498nm at 2nm intervals. Partial least square regression was used to investigate the correlation between spectral information and mechanical properties. Results show that spectral information is influenced by the major constituent components, as they are clustered according to polybutylene adipate-co-terephthalate content. Results for regression models using the spectral information as predictor of tensile properties achieved satisfactory results, with coefficients of prediction (R(2)C) of 0.83, 0.88 and 0.92 (calibration models) for elongation, tensile strength, and Young's modulus, respectively. Results corroborate the correlation of NIR spectra with tensile properties, showing that NIR spectroscopy has potential as a rapid analytical technology for non-destructive assessment of the mechanical properties of the films. PMID:26249590

  17. Mixing order of glidant and lubricant – Influence on powder and tablet properties

    PubMed Central

    Pingali, Kalyana; Mendez, Rafael; Lewis, Daniel; Michniak-Kohn, Bozena; Cuitino, Alberto; Muzzio, Fernando

    2014-01-01

    The main objective of the present work was to study the effect of mixing order of Cab-O-Sil (CS) and magnesium stearate (MgSt) and microlayers during mixing on blend and tablet properties. A first set of pharmaceutical blend containing Avicel PH200, Pharmatose and micronized acetaminophen was prepared with three mixing orders (mixing order-1: CS added first; mixing order-2: MgSt added first; mixing order-3: CS and MgSt added together). All the blends were subjected to a shear rate of 80 rpm and strain of 40, 160 and 640 revolutions in a controlled shear environment resulting in nine different blends. A second set of nine blends was prepared by replacing Avicel PH200 with Avicel PH102. A total of eighteen blends thus prepared were tested for powder hydrophobicity, powder flow, tablet weight, tablet hardness and tablet dissolution. Results indicated that powder hydrophobicity increased significantly for mixing order-1. Intermediate hydrophobic behavior was found for mixing order-3. Additionally, mixing order 1 resulted in improved powder flow properties, low weight variability, higher average tablet weight and slow drug release rates. Dissolution profiles obtained were found to be strongly dependent not only on the mixing order of flowing agents, but also on the strain and the resulting hydrophobicity. PMID:21356286

  18. Characterization of physical mixtures and directly compressed tablets of sulfamerazine polymorphs: implications on in vitro release characteristics.

    PubMed

    Roy, Shouvik; Alexander, Kenneth S; Riga, Alan T; Chatterjee, Koustuv

    2003-04-01

    The present study evaluates the effects of excipients, compression pressure, and relative humidity (RH) on the stability of sulfamerazine polymorphs (referred here as SMZ I and SMZ II) and their release from directly compressed tablets using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution analysis. SMZ I and SMZ II tablets were compressed with magnesium stearate (MGST), and microcrystalline cellulose (MCC) at 5000, 7500, and 10,000 lbs. pressures and stored at 40, 75, 95, and 100% RH conditions for 5 weeks. There were indications of possible drug-excipient interaction in the binary mixtures under different relative humidity conditions from the DSC data, but they could not be confirmed by PXRD because the crystal structures of the drug and excipients remained unaltered. The crystal structures of the polymorphs in the tablet also remained unaltered under the above conditions. There were, however, significant differences observed in the drug release properties of the two polymorphs. SMZ II was found in general to have a higher rate of drug release than SMZ I. Extensive gelation of MCC under higher moisture conditions, compression pressure during tableting, and inherent tabletability of the sulfamerazine crystals were factors that affected drug release. All these factors contributed towards prolonging the disintegration and deaggregation of the tablet particles and were therefore concluded to be the rate limiting steps for the dissolution process. PMID:12661061

  19. Effects of hexagonal boron nitride on dry compression mixture of Avicel DG and Starch 1500.

    PubMed

    Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

    2016-01-01

    The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) on a (1:1) binary mixture of Avicel DG and Starch 1500 after using the dry granulation-slugging method and compare it with conventional lubricants, such as magnesium stearate (MGST), glyceryl behenate (COMP) and stearic acid (STAC). MGST is one of the most commonly used lubricants in the pharmaceutical industry. However, it has several adverse effects on tablet properties. In our current study, we employed various methods to eradicate the work hardening phenomenon in dry granulation, and used HBN as a new lubricant to overcome the adverse effects of other lubricants on tablet properties. HBN was found to be as effective as MGST and did not show any significant adverse effects on the crushing strength or work hardening. From the scanning electron microscope (SEM) images, it was concluded that HBN distributed better than MGST. As well as showing better distribution, HBN's effect on disintegration was the least pronounced. Semi-quantitative weight percent distribution of B and N elements in the tablets was obtained using EDS (energy dispersive spectroscopy). Based on atomic force microscope (AFM) surface roughness images, formulations prepared with 1% HBN showed better plastic character than those prepared with MGST. PMID:25716058

  20. Comparison of Temperature and Additives Affecting the Stability of the Probiotic Weissella cibaria

    PubMed Central

    Kang, Mi-Sun; Kim, Youn-Shin; Lee, Hyun-Chul; Lim, Hoi-Soon

    2012-01-01

    Daily use of probiotic chewing gum might have a beneficial effect on oral health, and it is important that the viability of the probiotics be maintained in this food product. In this study, we examined the stability of probiotic chewing gum containing Weissella cibaria. We evaluated the effects of various factors, including temperature and additives, on the survival of freeze-dried probiotic W. cibaria powder. No changes in viability were detected during storage at 4℃ for 5 months, whereas the viability of bacteria stored at 20℃ decreased. The stability of probiotic chewing gum decreased steadily during storage at 20℃ for 4 weeks. The viability of the freeze-dried W. cibaria mixed with various additives, such as xylitol, sorbitol, menthol, sugar ester, magnesium stearate, and vitamin C, was determined over a 4-week storage period at 20℃. Most of the freeze-dried bacteria except for those mixed with menthol and vitamin C were generally stable during a 3-week storage period. Overall, our study showed that W. cibaria was more stable at 4℃ than that at 20℃. In addition, menthol and vitamin C had a detrimental effect on the storage stability of W. cibaria. This is the first study to examine the effects of various chewing gum additives on the stability of W. cibaria. Further studies will be needed to improve the stability of probiotic bacteria for developing a novel probiotic W. cibaria gum. PMID:23323221

  1. Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo.

    PubMed

    Huber, Alexandra; Kallerup, Rie S; Korsholm, Karen S; Franzyk, Henrik; Lepenies, Bernd; Christensen, Dennis; Foged, Camilla; Lang, Roland

    2016-08-01

    The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle. PMID:27252171

  2. Nickel-cobalt nanoparticles supported on single-walled carbon nanotubes and their catalytic hydrogenation activity.

    PubMed

    Lekgoathi, Mpho D S; Augustyn, Willem G; Heveling, Josef

    2011-08-01

    Single-walled carbon nanotubes were synthesized from graphite using the arc discharge technique. A nickel/yttrium/graphite mixture was used as the catalyst. After purification by sonication in a Triton X-100 solution, nickel-cobalt metal nanoparticles were deposited on the surface of the single-walled carbon nanotubes. The resulting material and/or the nanotubes themselves were characterized by physisorption, Raman spectroscopy, high-resolution transition electron microscopy and X-ray diffraction. Raman spectroscopy indicates that the nanotubes, prepared by the arc discharge technique, are semi-conducting with a diameter centering at 1.4 nm. The average nickel-cobalt particle size is estimated to be in the region of 8 nm. The catalytic activity of the material was examined for the hydrogenation of unsaturated fatty acid methyl esters obtained from avocado oil. The carbon nanotube supported nickel-cobalt particles effectively hydrogenate polyunsaturated methyl linoleate to monounsaturated methyl oleate. In contrast to a conventional nickel on kieselghur catalyst, further hydrogenation of methyl oleate to undesired methyl stearate was not observed. PMID:22103112

  3. Lipid-based nanocarrier for quercetin delivery: system characterization and molecular interactions studies.

    PubMed

    Hädrich, Gabriela; Monteiro, Samantha Oliveira; Rodrigues, Marisa Raquel; de Lima, Vânia Rodrigues; Putaux, Jean-Luc; Bidone, Juliana; Teixeira, Helder Ferreira; Muccillo-Baisch, Ana Luiza; Dora, Cristiana Lima

    2016-07-01

    The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid-polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20 nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability. PMID:26571009

  4. A tiered analytical approach for investigating poor quality emergency contraceptives.

    PubMed

    Monge, María Eugenia; Dwivedi, Prabha; Zhou, Manshui; Payne, Michael; Harris, Chris; House, Blaine; Juggins, Yvonne; Cizmarik, Peter; Newton, Paul N; Fernández, Facundo M; Jenkins, David

    2014-01-01

    Reproductive health has been deleteriously affected by poor quality medicines. Emergency contraceptive pills (ECPs) are an important birth control method that women can use after unprotected coitus for reducing the risk of pregnancy. In response to the detection of poor quality ECPs commercially available in the Peruvian market we developed a tiered multi-platform analytical strategy. In a survey to assess ECP medicine quality in Peru, 7 out of 25 different batches showed inadequate release of levonorgestrel by dissolution testing or improper amounts of active ingredient. One batch was found to contain a wrong active ingredient, with no detectable levonorgestrel. By combining ultrahigh performance liquid chromatography-ion mobility spectrometry-mass spectrometry (UHPLC-IMS-MS) and direct analysis in real time MS (DART-MS) the unknown compound was identified as the antibiotic sulfamethoxazole. Quantitation by UHPLC-triple quadrupole tandem MS (QqQ-MS/MS) indicated that the wrong ingredient was present in the ECP sample at levels which could have significant physiological effects. Further chemical characterization of the poor quality ECP samples included the identification of the excipients by 2D Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY 1H NMR) indicating the presence of lactose and magnesium stearate. PMID:24748219

  5. Characterization of tableting properties measured with a multi-functional compaction instrument for several pharmaceutical excipients and actual tablet formulations.

    PubMed

    Osamura, Takashi; Takeuchi, Yoshiko; Onodera, Risako; Kitamura, Masahiro; Takahashi, Yoshiteru; Tahara, Kohei; Takeuchi, Hirofumi

    2016-08-20

    Before designing tablet formulations, it is important to understand the "Tableting Properties" of excipients and API (active pharmaceutical ingredient) powders. Those properties refer to "Compressibility", "Compactability" and "Manufacturability", which are difficult to evaluate quantitatively. In this study, we aimed to evaluate the "Tableting Properties" by using a benchtop single-punch tablet press, developed recently to measure these parameters using a single device. In order to facilitate understanding of the results visually, we proposed a new plot, where the X-axis showed the tensile fracture stress and the Y-axis showed the ejection stress. This plot, which is composed of four regions, shows the combination of "Compactability" and "Manufacturability". We confirmed the ability of this device to evaluate the characteristics of typical pharmaceutical additives as a value of "Tableting Properties". Losartan potassium was used as an API, and Dilactose R and MCC as an excipient with good "Tableting Properties". The ejection stresses of losartan potassium and Dilactose R were very high. An increase in magnesium stearate shifted the point along the Y-axis in this plot, and it meant an improvement in "Manufacturability". It was confirmed that the device and plot are useful in designing formulations efficiently using a small amount of sample powders. PMID:27184101

  6. Affinity purification and characterization of a biodegradable plastic-degrading enzyme from a yeast isolated from the larval midgut of a stag beetle, Aegus laevicollis.

    PubMed

    Suzuki, Ken; Sakamoto, Hironori; Shinozaki, Yukiko; Tabata, Jun; Watanabe, Takashi; Mochizuki, Atsushi; Koitabashi, Motoo; Fujii, Takeshi; Tsushima, Seiya; Kitamoto, Hiroko K

    2013-09-01

    Two yeast strains, which have the ability to degrade biodegradable plastic films, were isolated from the larval midgut of a stag beetle, Aegus laevicollis. Both of them are most closely related to Cryptococcus magnus and could degrade biodegradable plastic (BP) films made of poly(butylene succinate) (PBS) and poly(butylene succinate-co-adipate) (PBSA) effectively. A BP-degrading enzyme was purified from the culture broth of one of the isolated strains employing a newly developed affinity purification method based on the binding action of the enzyme to the substrate (emulsified PBSA) and its subsequent degradative action toward the substrate. Partial amino acid sequences of this enzyme suggested that it belongs to the cutinase family, and thus, the enzyme was named CmCut1. It has a molecular mass of 21 kDa and a degradative activity for emulsified PBSA which was significantly enhanced by the simultaneous presence of Ca(2+) or Mg(2+) at a concentration of about 2.5 mM. Its optimal pH was 7.5, and the optimal temperature was 40 °C. It showed a broad substrate specificity for p-nitrophenyl (pNP)-fatty acid esters ranging from pNP-acetate (C2) to pNP-stearate (C18) and films of PBSA, PBS, poly(ε-caprolactone), and poly(lactic acid). PMID:23224497

  7. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages[S

    PubMed Central

    L'homme, Laurent; Esser, Nathalie; Riva, Laura; Scheen, André; Paquot, Nicolas; Piette, Jacques; Legrand-Poels, Sylvie

    2013-01-01

    The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. PMID:24006511

  8. Anaphylaxis to Spirulina confirmed by skin prick test with ingredients of Spirulina tablets.

    PubMed

    Le, Thuy-My; Knulst, André C; Röckmann, Heike

    2014-12-01

    Spirulina (Arthrospira platensis), blue-green microalgae, has high content in proteins, γ-linoleic acid and vitamins and therefore gained popularity as food supplement. According to the Food and Agriculture Organization of the United Nations Spirulina is also an interesting alternative and sustainable protein source with the growing world population. We present a case of a 17-year-old male, who developed anaphylaxis the first time he ingested a Spirulina tablet. Skin prick test with diluted Spirulina tablet was positive. Further skin prick testing with separated ingredients (Spirulina platensis algae, silicon dioxide, inulin and magnesium stearate) was only positive for Spirulina platensis algae and negative in controls, confirming the allergy was caused by Spirulina and not by one of the additives. This case report shows that diagnosis of Spirulina allergy can safely be made by skin prick test with dilutions of the A. platensis or even more simple by skin prick test with the diluted tablet. Since Spirulina has gained popularity as food and nutritional supplement, it is important to realize the potential risk of this dietary supplement. Before Spirulina is produced and consumed on a wider scale, allergenicity risk assessment should be performed, including investigation of potential crossreactivity with well-known inhalant allergens and foods. PMID:25445756

  9. Effect of storage at specified temperature and humidity on properties of three directly compressible tablet formulations.

    PubMed

    Horhota, S T; Burgio, J; Lonski, L; Rhodes, C T

    1976-12-01

    Direct compression tablets containing sodium starch glycolate, an alginate derivative, or povidone as a disintegrant, magnesium stearate as a lubricant, amaranth as a tracer, and dibasic calcium phosphate dihydrate as the matrix were stored for 30 days at 23 degrees and 75% relative humidity (R.H.), 45 degrees and 75% R.H., and 65 degrees and 40% R.H. Samples were evaluated after 0, 10, 20, and 30 days for size, hardness, and dissolution characteristics. Although no significant changes in the dimensions or hardness of the three tablet formulations, prepared at three different compaction pressures, were observed, the dissolution efficiency of the systems showed significant changes, some systems dissolving more rapidly and some more slowly after storage. In some cases, the changes were so substantial as to indicate the possibility of significant changes of the bioavailability of drugs formulated in such systems. The relevance of this work to the problem of evaluating aging effects on the physical properties of tablets is discussed. PMID:1032656

  10. Efficient water removal in lipase-catalyzed esterifications using a low-boiling-point azeotrope.

    PubMed

    Yan, Youchun; Bornscheuer, Uwe T; Schmid, Rolf D

    2002-04-01

    High conversions in lipase-catalyzed syntheses of esters from free acyl donors and an alcohol requires efficient removal of water preferentially at temperatures compatible to enzyme activity. Using a lipase B from Candida antarctica (CAL-B)-mediated synthesis of sugar fatty-acid esters, we show that a mixture of ethyl methylketone (EMK) and hexane (best ratio: 4:1, vo/vo) allows efficient removal of water generated during esterification. Azeotropic distillation of the solvent mixture (composition: 26% EMK, 55% hexane, 19% water) takes place at 59 degrees C, which closely matches the optimum temperature reported for CAL-B. Water is then removed from the azeotrope by membrane vapor permeation. In case of glucose stearate, 93% yield was achieved after 48 h using an equimolar ratio of glucose and stearic acid. CAL-B could be reused for seven reaction cycles, with 86% residual activity after 14 d total reaction time at 59 degrees C. A decrease in fatty-acid chain length as well as increasing temperatures (75 degrees C) resulted in lower conversions. In addition, immobilization of CAL-B on a magnetic polypropylene carrier (EP 100) facilitated separation of the biocatalyst. PMID:11857278

  11. Primary structure of a new phosphocholine-containing glycoglycerolipid of Mycoplasma fermentans.

    PubMed

    Zähringer, U; Wagner, F; Rietschel, E T; Ben-Menachem, G; Deutsch, J; Rottem, S

    1997-10-17

    The chemical structure of a novel phosphocholine-containing glycoglycerolipid, the major polar lipid in the cell membrane of Mycoplasma fermentans PG18, was investigated by chemical analyses, gas-liquid chromatography-mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, as well as one- and two-dimensional homo- and heteronuclear NMR spectroscopy and identified as 6'-O-(3"-phosphocholine-2"-amino-1"-phospho-1", 3"-propanediol)-alpha-D-glucopyranosyl-(1'-->3)-1,2-diacyl-glycerol (MfGL-II). Palmitate (16:0) and stearate (18:0), in a 3.6:1 molar ratio, constitute the major fatty acids present. MALDI-TOF mass spectrometry revealed two major pseudomolecular ions at m/z 1049.5 [MI + H]+ and 1077.3 [MII + H]+ representing a dipalmitoyl as the major component and a palmitoyl-stearoyl structure as a minor component. This is the first report of 2-amino-1,3-propanediol-1,3-bisphosphate present in a natural product. This glycoglycerolipid is the second phosphocholine-containing glycoglycerolipid found in M. fermentans. PMID:9334195

  12. Comparison of Temperature and Additives Affecting the Stability of the Probiotic Weissella cibaria.

    PubMed

    Kang, Mi-Sun; Kim, Youn-Shin; Lee, Hyun-Chul; Lim, Hoi-Soon; Oh, Jong-Suk

    2012-12-01

    Daily use of probiotic chewing gum might have a beneficial effect on oral health, and it is important that the viability of the probiotics be maintained in this food product. In this study, we examined the stability of probiotic chewing gum containing Weissella cibaria. We evaluated the effects of various factors, including temperature and additives, on the survival of freeze-dried probiotic W. cibaria powder. No changes in viability were detected during storage at 4℃ for 5 months, whereas the viability of bacteria stored at 20℃ decreased. The stability of probiotic chewing gum decreased steadily during storage at 20℃ for 4 weeks. The viability of the freeze-dried W. cibaria mixed with various additives, such as xylitol, sorbitol, menthol, sugar ester, magnesium stearate, and vitamin C, was determined over a 4-week storage period at 20℃. Most of the freeze-dried bacteria except for those mixed with menthol and vitamin C were generally stable during a 3-week storage period. Overall, our study showed that W. cibaria was more stable at 4℃ than that at 20℃. In addition, menthol and vitamin C had a detrimental effect on the storage stability of W. cibaria. This is the first study to examine the effects of various chewing gum additives on the stability of W. cibaria. Further studies will be needed to improve the stability of probiotic bacteria for developing a novel probiotic W. cibaria gum. PMID:23323221

  13. Study of the compressibility of chewing gum and its applicability as an oral drug delivery system.

    PubMed

    Jójárt, I; Kása, P; Kelemen, A; Pintye-Hódi, K

    2016-01-01

    Medicated chewing gum tablets were prepared and evaluated as an oral drug delivery system. The morphology and surface free energy of the components were characterized, and the tablets were prepared by direct compression with an instrumented eccentric tableting machine. The compressibility, the porosity and the texture of the tablets were investigated and the dissolution of the active pharmaceutical ingredient (caffeine) from them was tested with a specially-developed method. Cafosa gum base is a co-processed product which is compressible. Because of the sticking of the tablets to the punches and the high friction that arises during ejection from the die, the use of lubricants and suitable (e.g. Teflon-coated) punches is necessary on a production scale. For this purpose, magnesium stearate with high specific surface area was applied. The release of caffeine in response to the mechanical effect applied proved to be rapid and quantitative and the profile closely obeyed the Korsmeyer-Peppas equation, which is valid in the case of matrix systems. Medicated chewing gum tablets can be used as matrix tablets for oral pharmaceutical administration. PMID:25673279

  14. NIR-responsive silica-coated NaYbF4:Er/Tm/Ho upconversion fluorescent nanoparticles with tunable emission colors and their applications in immunolabeling and fluorescent imaging of cancer cells

    PubMed Central

    Wang, Meng; Mi, Congcong; Zhang, Yixin; Liu, Jinling; Li, Feng; Mao, Chuanbin; Xu, Shukun

    2009-01-01

    NaYbF4: RE upconversion (UC) fluorescent nanoparticles (NPs) were synthesized with variable rare-earth dopants (RE= Er3+, Tm3+, or Ho3+, or a combination of these ions), from rare-earth stearate precursors in a water-ethanol-oleic acid system by using a two-phase solvothermal method. The NPs were shown to emit visible light such as orange, yellow, green, cyan, blue or pink light in response to near infrared (NIR) irradiation, and their emission colors could be simply tuned by changing either the co-dopant concentration or dopant species. The UC NPs were well-dispersed and spherical with an average size of 15~35 nm. They emitted strong UC fluorescence under the 980 nm NIR excitation. The effects of solvothermal reaction time and temperature on nanoparticle size and phase structure as well as UC fluorescence intensity were systematically studied. Water dispersibility was achieved by forming a silica coat on the surface of the UC NPs. After animo-functionalization, the silica-coated UC NPs were chemically conjugated with the rabbit anti-CEA8 antibody and then used as fluorescent biolabels for the immunolabeling and imaging of HeLa cells. The NIR-responsive multicolor visible light emission of these UC NPs will enable potential applications in biolabeling and multiplexed analysis because NIR light can penetrate tissue as deep as several inches and is safe to human body. PMID:20160878

  15. Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

    PubMed

    Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

    2012-01-01

    A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics. PMID:22878814

  16. Formulation of indomethacin colon targeted delivery systems using polysaccharides as carriers by applying liquisolid technique.

    PubMed

    Elkhodairy, Kadria A; Elsaghir, Hanna A; Al-Subayiel, Amal M

    2014-01-01

    The present study aimed at the formulation of matrix tablets for colon-specific drug delivery (CSDD) system of indomethacin (IDM) by applying liquisolid (LS) technique. A CSDD system based on time-dependent polymethacrylates and enzyme degradable polysaccharides was established. Eudragit RL 100 (E-RL 100) was employed as time-dependent polymer, whereas bacterial degradable polysaccharides were presented as LS systems loaded with the drug. Indomethacin-loaded LS systems were prepared using different polysaccharides, namely, guar gum (GG), pectin (PEC), and chitosan (CH), as carriers separately or in mixtures of different ratios of 1:3, 1:1, and 3:1. Liquisolid systems that displayed promising results concerning drug release rate in both pH 1.2 and pH 6.8 were compressed into tablets after the addition of the calculated amount of E-RL 100 and lubrication with magnesium stearate and talc in the ratio of 1:9. It was found that E-RL 100 improved the flowability and compressibility of all LS formulations. The release data revealed that all formulations succeeded to sustain drug release over a period of 24 hours. Stability study indicated that PEC-based LS system as well as its matrix tablets was stable over the period of storage (one year) and could provide a minimum shelf life of two years. PMID:24971345

  17. Isolation and biochemical characterization of two lipases from a metagenomic library of China Holstein cow rumen.

    PubMed

    Liu, Kailang; Wang, Jiaqi; Bu, Dengpan; Zhao, Shengguo; McSweeney, Chris; Yu, Ping; Li, Dan

    2009-08-01

    Two novel lipase genes RlipE1 and RlipE2 which encoded 361- and 265-amino acid peptides, respectively, were recovered from a metagenomic library of the rumen microbiota of Chinese Holstein cows. A BLAST search revealed a high similarity (90%) between RlipE2 and a carboxylesterase from Thermosinus carboxydivorans Nor1, while there was a low similarity (below 50%) between RlipE1 and other lipases. Phylogenetic analysis indicated that RlipE2 clustered with the lipolytic enzymes from family V while RlipE1 clustered with six other putative bacterial lipases which might constitute a new subfamily. The recombinant lipases were thermally unstable and retained 60% activity over a pH range of 6.5-8.5. Substrate specificity assay indicated that both enzymes had higher hydrolytic activity toward laurate (C(12)), palmitate (C(16)) and stearate (C(18)). The novel phylogenetic affiliation and high specificity of both enzymes for long-chain fatty acid make them interesting targets for manipulation of rumen lipid metabolism. PMID:19486892

  18. Application of silver nanoparticles to the chemiluminescence determination of cefditoren pivoxil using the luminol-ferricyanide system.

    PubMed

    Alarfaj, Nawal A; Aly, Fatma A; El-Tohamy, Maha F

    2015-02-01

    A new simple, accurate and sensitive sequential injection analysis chemiluminescence (CL) detection method for the determination of cefditoren pivoxil (CTP) has been developed. The developed method was based on the enhancement effect of silver nanoparticles on the CL signal arising from a luminol-potassium ferricyanide reaction in the presence of CTP. The optimum conditions relevant to the effect of luminol, potassium ferricyanide and silver nanoparticle concentrations were investigated. The proposed method showed linear relationships between relative CL intensity and the investigated drug concentration at the range 0.001-5000 ng/mL, (r = 0.9998, n = 12) with a detection limit of 0.5 pg/mL and quantification limit of 0.001 ng/mL. The relative standard deviation was 1.6%. The proposed method was employed for the determination of CTP in bulk drug, in its pharmaceutical dosage forms and biological fluids such as human serum and urine. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated. In addition, the interference of some related cephalosporins was tested. No interference was recorded. The obtained sequential injection analysis-CL results were statistically compared with those from a reported method and did not show any significant differences. PMID:24850667

  19. Enzymatic synthesis of fatty acid ethyl esters by utilizing camellia oil soapstocks and diethyl carbonate.

    PubMed

    Wang, Yingying; Cao, Xuejun

    2011-11-01

    This study was reported on a novel process for fatty acid ethyl esters preparation by transesterification and esterification from renewable low-cost feedstock camellia oil soapstocks and friendly acyl acceptor diethyl carbonate. The main components of product were 83.9% ethyl oleate, 8.9% ethyl palmitate, 4.7% ethyl linoleate and 2.1% ethyl stearate, which could be used as eco-friendly renewable resources or additives of industrial solvent and fossil fuel. The effects of molar ratio of diethyl carbonate to soapstocks oil, lipases, organic solvent, reaction temperature and time were investigated, and process conditions were optimized. The yield was up to 98.4% in solvent-free system with molar ratio of diethyl carbonate to soapstocks oil 3:1 and 5% Novozym 435 (based on the weight of soapstocks oil) at 50 °C and 180 rpm for 24 h. Moreover, there was no obvious loss in the yield after lipases were reused for 10 batches without treatment under optimized conditions. PMID:21958524

  20. Exploring the Halal Status of Cardiovascular, Endocrine, and Respiratory Group of Medications

    PubMed Central

    Sarriff, Azmi; Abdul razzaq, Hadeer Akram

    2013-01-01

    Muslim consumers have special needs in medical treatment that differ from non-Muslim consumers. In particular, there is a growing demand among Muslim consumers for Halal medications. This descriptive exploratory study aims to determine the Halal status of selected cardiovascular, endocrine, and respiratory medications stored in an out-patient pharmacy in a Malaysian governmental hospital. Sources of active ingredients and excipients for each product were assessed for Halal status based on available information obtained from product leaflets, the Medical Information Management System (MIMS) website, or manufacturers. Halal status was based on the products’ sources and categorized into Halal, Mushbooh, or Haram. The proportions of Halal, Mushbooh, and Haram products were at 19.1%, 57.1%, and 23.8%, respectively. The percentage of active ingredients for cardiovascular/endocrine products that were assessed as Haram was 5.3%; for respiratory medications, it was only 1.1%. For excipients, 1.7% and 4.8% fall under the category of Haram for cardiovascular/endocrine products and respiratory products, respectively. Ethanol and magnesium stearate were found to be the common substances that were categorized as Haram and Mushbooh. PMID:23785257

  1. Comparative studies of binding potential of Prunus armeniaca and Prunus domestica gums in tablets formulations.

    PubMed

    Rahim, Haroon; Khan, Mir Azam; Sadiq, Abdul; Khan, Shahzeb; Chishti, Kamran Ahmad; Rahman, Inayat U

    2015-05-01

    The current study was undertaken to compare the binding potential of Prunus armeniaca L. and Prunus domestica L. gums in tablets' formulations. Tablet batches (F-1 to F-9) were prepared Diclofenac sodium as model drug using 5%, 7.5% and 10% of each Prunus armeniaca L., Prunus domestica L. gums as binder. PVP K30 was used as a standard binder. Magnesium stearate was used as lubricant. Flow properties of granules (like bulk density, tapped density, Carr's index, Hausner's ratio, angle of repose) as well as the physical parameters of compressed tablets including hardness, friability, thickness and disintegration time were determined. Flow parameters of granules of all the batches were found good. Physical parameters (drug content, weight variation, thickness, hardness, friability, disintegration time) of formulated tablets were found within limit when tested. The dissolution studies showed that tablets formulations containing each Prunus domestica showed better binding capacity compared to Prunus armeniaca gum. The binding potential increased as the concentration of gums increased. The FTIR spectroscopic investigation showed that the formulations containing plant gum are compatible with the drug and other excipients used. PMID:26004724

  2. The N-terminal SH4 region of the Src family kinase Fyn is modified by methylation and heterogeneous fatty acylation: role in membrane targeting, cell adhesion, and spreading.

    PubMed

    Liang, Xiquan; Lu, Yun; Wilkes, Meredith; Neubert, Thomas A; Resh, Marilyn D

    2004-02-27

    The N-terminal SH4 domain of Src family kinases is responsible for promoting membrane binding and plasma membrane targeting. Most Src family kinases contain an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with myristate and palmitate after removal of methionine. Previous studies of Src family kinase fatty acylation have relied on radiolabeling of cells with radioactive fatty acids. Although this method is useful for verifying that a given fatty acid is attached to a protein, it does not reveal whether other fatty acids or other modifying groups are attached to the protein. Here we use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify fatty acylated species of the Src family kinase Fyn. Our results reveal that Fyn is efficiently myristoylated and that some of the myristoylated proteins are also heterogeneously S-acylated with palmitate, palmitoleate, stearate, or oleate. Furthermore, we show for the first time that Fyn is trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both myristoylation and palmitoylation were required for methylation of Fyn. However, a general methylation inhibitor had no inhibitory effect on myristoylation and palmitoylation of Fyn, suggesting that methylation occurs after myristoylation and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to promote cell adhesion and spreading, suggesting that methylation is important for Fyn function. PMID:14660555

  3. Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium for detection of alcohol abuse during pregnancy: Correlation study between both biomarkers.

    PubMed

    Cabarcos, Pamela; Tabernero, María Jesús; Otero, José Luís; Míguez, Martha; Bermejo, Ana María; Martello, Simona; De Giovanni, Nadia; Chiarotti, Marcello

    2014-11-01

    This article presents results from 47 meconium samples, which were analyzed for fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for detection of gestational alcohol consumption. A validated microwave assisted extraction (MAE) method in combination with GC-MS developed in the Institute of Forensic Science (Santiago de Compostela) was used for FAEE and the cumulative concentration of ethyl myristate, ethyl palmitate and ethyl stearate with a cut-off of 600ng/g was applied for interpretation. A simple method for identification and quantification of EtG has been evaluated by ultrasonication followed solid phase extraction (SPE). Successful validation parameters were obtained for both biochemical markers of alcohol intake. FAEE and EtG concentrations in meconium ranged between values lower than LOD and 32,892ng/g or 218ng/g respectively. We have analyzed FAEE and EtG in the same meconium aliquot, enabling comparison of the efficiency of gestational ethanol exposure detection. Certain agreement between the two biomarkers was found as they are both a very specific alcohol markers, making it a useful analysis for confirmation. PMID:25137651

  4. Combination effect of physical and gustatory taste masking for propiverine hydrochloride orally disintegrating tablets on palatability.

    PubMed

    Matsui, Rakan; Uchida, Shinya; Namiki, Noriyuki

    2015-01-01

    Orally disintegrating tablets (ODTs) containing propiverine hydrochloride (which is extremely bitter and leaves a feeling of numbness in the mouth) were prepared with a combined use of physical and organoleptic taste masking. Propiverine-loaded masking particles (PLMPs) were prepared with different amounts of gastric-soluble coatings as physical masking. ODTs without organoleptic masking were prepared by mixing each group of PLMPs with Ludiflash®, crospovidone, and magnesium stearate. ODTs with organoleptic masking were also prepared by addition of L-menthol, aspartame, thaumatin, and cinnamon. Fifteen-minute dissolution of propiverine in solutions with pH 1.2 was ≥ 85% for all ODTs, whereas that in pH 6.8 solutions was ≤ 85% and increased with physical masking. A single blind randomized crossover trial was conducted. Ten healthy volunteers were asked to quantify the bitterness, numbness, and overall palatability using a 100-mm visual analog scale (VAS) at the period of disintegration as well as 1 and 5 min later. VAS scores of bitterness, numbness, and overall palatability improved along with increasing amounts of physical masking, and the effects persisted for 5 min. VAS scores for numbness increased over time regardless of the amount of physical masking. Bitterness, numbness, and overall palatability were significantly improved by organoleptic masking if the amount of physical masking was small. Combined use of physical and organoleptic masking is useful for improving palatability of ODTs containing propiverine. PMID:25744453

  5. Dispersibility of lactose fines as compared to API in dry powders for inhalation.

    PubMed

    Thalberg, Kyrre; Åslund, Simon; Skogevall, Marcus; Andersson, Patrik

    2016-05-17

    This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. Fine particle assessment demonstrates that the lactose fines have higher dispersibility than the API. For standard formulations, processing time has a limited effect on the Fine Particle Fraction (FPF). For formulations containing magnesium stearate (MgSt), FPF of BDP is heavily influenced by processing time, with an initial increase, followed by a decrease at longer mixing times. An equation modeling the observed behavior is presented. Surprisingly, the dispersibility of the lactose fines present in the same formulation remains unaffected by mixing time. Magnesium analysis demonstrates that MgSt is transferred to the fine particles during the mixing process, thus lubrication both BDP and lactose fines, which leads to an increased FPF. Dry particle sizing of the formulations reveals a loss of fine particles at longer mixing times. Incorporation of fine particles into the carrier surfaces is believed to be behind this, and is hence a mechanism of importance as regards the dispersion performance of dry powders for inhalation. PMID:26965200

  6. Preparation and testing of a solid secondary plasticizer for PVC produced by chemical degradation of post-consumer PET.

    PubMed

    Amaro, Lucía Pérez; Coiai, Serena; Ciardelli, Francesco; Passaglia, Elisa

    2015-12-01

    Post-consumer poly(ethylene therephthalate) (PET) obtained from milled water bottles was chemically degraded by glycolysis, using suitable amounts of diethylene glycol (DEG) and Ca/Zn stearate as catalyst system. The process was carried out by employing a melt mixer as the chemical reactor, which is the facility generally used for plastic compounding. The degraded PET products were first characterized from structural and thermal point of view by Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance ((1)H NMR), Size exclusion chromatography (SEC) Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA), and thereafter used alone or together with di(2-ethylhexyl) phthalate (DEHP) in poly(vinyl chloride) PVC formulations. The plasticization was, in fact, accomplished by using a binary system consisting of DEHP as primary plasticizer and a degraded PET product as secondary plasticizer (SP). The obtained materials were characterized through the main methods used to assess flexible PVC compounds: hardness in Shore A scale, thermal properties and quantitative migration of the plasticizer. The solid secondary plasticizer obtained from post-consumer PET improves both the processing characteristics and the thermal stability of the final flexible PVC compounds while maintaining their hardness within the top values of the Shore A scale. In addition, a considerable reduction of the plasticizers migration (23%) was obtained by optimizing the formulation. PMID:26376120

  7. A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses.

    PubMed

    Lupi, Francesca R; Shakeel, Ahmad; Greco, Valeria; Oliviero Rossi, Cesare; Baldino, Noemi; Gabriele, Domenico

    2016-12-01

    Bigels are biphasic systems formed by water-based hydrogels and oil-based organogels, mainly studied, in the last few years, for pharmaceutical and cosmetic application focused on the controlled delivery of both lipophilic and hydrophilic active agents. The rheological properties of bigels depend on both the amount and the rheological characteristics of single structured phases. Moreover, it can be expected that, at large fractions of one of the starting gels, systems more complex than oil-in-water or water-in-oil can be obtained, yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were investigated from a microstructural (i.e. microscopy and electrical conductivity tests) and rheological point of view. The hydrogel was prepared by using a low-methoxyl pectin whereas the organogel was prepared by using olive oil and, as gelator, a mixture of glyceryl stearate and policosanol. Model bigels were obtained by increasing the amount of organogel mixed with the hydrogel, and microstructural characterisation evidenced an organogel-in-hydrogel behaviour for all investigated samples, even though at the highest organogel content a more complex structure seems to arise. A semi-empirical model, based on theoretical equations developed for suspensions of elastic spheres in elastic media, was proposed to relate bigel rheological properties to single phase properties and fractions. PMID:27612723

  8. Catalytic hydrogenation of high volatile bituminous coal and various coal extracts: Final report for 1986/1987 SOMED Project

    SciTech Connect

    Kispert, L.D.

    1987-09-01

    Model compounds, naphthalene, quinolines, and isoquinoline (possible extracts of coal) were selectively hydrogenated to 1,2,3,4-tetrahydro products by a Ziegler type catalyst (I) made of cobalt stearate and triethyl aluminum (1:2 molar ratio) in hexane solvent and temperatures as low as 22/degree/C and hydrogen pressure of 700-800 psi. It was established that a hydrogen pressure greater than 300 psi is crucial for hydrogenation to occur. For instance, at a pressure of 300 psi, only 5% reduction of naphthalene was observed with the rest of the starting material remaining intact. The important feature of this Ziegler catalyst is that it works best at low temperatures, moderate pressures and short reaction times, most unusual for a Ziegler catalyst. The catalyst, however, failed to bring about any reduction with such compounts as 8-nitro-2-methylquinoling, 4-chloro-2-methylquinoline, phenol, and dibenzothiophene. These failures are not surprising as nitro compounds are known to interact with and deactivate similar catalysts and homogeneous transition metal catalysts usually fail in the present of sulfur containing compounds. 23 refs., 2 tabs.

  9. Catalytic hydrogenation of bituminous coal and various coal extracts: Final report for the 1987--1988 SOMED project year

    SciTech Connect

    Kispert, L.D.

    1988-01-01

    Naphthalene (II), quinoline (III), isoquinoline (IV), 6-methylquinoline (V) and 2-methylquinoline (VI) can be hydrogenated selectively to form 1,2,3,4-tetrahydronaphthalene (VII) (100% yield at 22/degree/C), 1,2,3,4-tetrahydroquinoline (VIII) (73% yield at 22/degree/C), 1,2,3,4-tetrahydroisoquinoline (IX) (70% yield at 90/degree/C), 6-methyl-1,2,3,4-tetrahydroquinoline (X) (100% at 90/degree/C), and 2-methyl-1,2,3,4-tetrahydroquinoline (XI) (76% at 90/degree/C) by use of the Ziegler-type catalyst Co(stearate)/sub 2/-AlEt/sub 3/ (I) in a hexane solvent at a hydrogen pressure of 700 psi. Catalyst (I) does not hydrogenate dibenzothiophene, nitroquinolines or 4-chloro-2-methylquinoline. By extrapolating these results, a maximum yield of hydrogenation product from low sulfur coal using catalyst (I) was achieved by either maintaining the temperatures as low as 100/degree/C for a long period of time or by conducting the process at high temperature (/approximately/150/degree/C) for a short period of time. Hydrogenation of low sulfur coal resulted in a hydrogenated liquid product equal to 20% of the initial coal weight at 100/degree/C and 800 psi hydrogen pressure. Microanalysis of the product showed the hydrogen content had doubled. On the other hand, attempts to hydrogenate high sulfur content coal (Illinois No. 6), gave unsatisfactory results. 27 refs., 3 tabs.

  10. Catalytic hydrogenation of high volatility bituminous coal and various coal extracts: final report for 1986-1987. SOMED (School of Mines and Energy Development) project. Faculty research report

    SciTech Connect

    Kispert, L.D.

    1987-09-01

    Model compounds, naphthalene, quinolines, and isoquinoline (possible extracts of coal) were selectively hydrogenated to 1,2,3,4-tetrahydro products by a Ziegler-type catalyst (I) made of cobalt stearate and triethyl aluminum (1:2 molar ratio) in hexane solvent and temperatures as low as 22/sup 0/C and hydrogen pressure of 700-800 psi. It was established that a hydrogen pressure greater than 300 psi is crucial for hydrogenation to occur. The important feature of the Ziegler catalyst is that it works best at low temperatures, moderate pressures, and short reaction times, most unusual for a Ziegler catalyst. A sample of solvent-refined coal (SRC) (less than .9% sulfur) was previously liquefied at 90 degree C and hydrogen pressure of 800 psi in a period of 24 h. In this, a sample of Illinois No. 6 high-volatility bitiminous coal (a high-sulfur coal, 5.8% S) was treated with catalyst (I) under the same conditions as applied for SRC. Analysis indicated a 10% conversion for the high-sulfur coal.

  11. Enzymatically catalyzed synthesis of low-calorie structured lipid in a solvent-free system: optimization by response surface methodology.

    PubMed

    Han, Lu; Xu, Zijian; Huang, Jianhua; Meng, Zong; Liu, Yuanfa; Wang, Xingguo

    2011-12-14

    A kind of low-calorie structured lipid (LCSL) was obtained by interesterification of tributyrin (TB) and methyl stearate (St-ME), catalyzed by a commercially immobilized 1,3-specific lipase, Lipozyme RM IM from Rhizomucor miehei . The condition optimization of the process was conducted by using response surface methodology (RSM). The optimal conditions for highest conversion of St-ME and lowest content LLL-TAG (SSS and SSP; S, stearic acid; P, palmitic acid) were determined to be a reaction time 6.52 h, a substrate molar ratio (St-ME:TB) of 1.77:1, and an enzyme amount of 10.34% at a reaction temperature of 65 °C; under these conditions, the actually measured conversion of St-ME and content of LLL-TAG were 78.47 and 4.89% respectively, in good agreement with predicted values. The target product under optimal conditions after short-range molecular distillation showed solid fat content (SFC) values similar to those of cocoa butter substitutes (CBS), cocoa butter equivalent (CBE), and cocoa butters (CB), indicating its application for inclusion with other fats as cocoa butter substitutes. PMID:22082136

  12. [Study on sustained release preparations of Epimedium component].

    PubMed

    Yan, Hong-mei; Ding, Dong-mei; Zhang, Zhen-hai; Sun, E; Song, Jie; Jia, Xiao-bin

    2015-04-01

    The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations. PMID:26281584

  13. Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion.

    PubMed

    Wahl, Patrick R; Treffer, Daniel; Mohr, Stefan; Roblegg, Eva; Koscher, Gerold; Khinast, Johannes G

    2013-10-15

    Implementation of continuous manufacturing in the pharmaceutical industry requires tight process control. This study focuses on a PAT strategy for hot melt extrusion of vegetable calcium stearate (CaSt) as matrix carrier and paracetamol as active pharmaceutical ingredient (API). The extrusion was monitored using in-line near-infrared (NIR) spectroscopy. A NIR probe was located in the section between the extrusion screws and the die, using a novel design of the die channel. A chemometric model was developed based on premixes at defined concentrations and was implemented in SIPAT for real time API concentration monitoring. Subsequently, step experiments were performed for different API concentrations, screw speeds and screw designs. The predicted API concentration was in good agreement with the pre-set concentrations. The transition from one API plateau to another was a smooth curve due to the mixing behaviour of the extruder. The accuracy of the model was confirmed via offline HPLC analysis. The screw design was determined as the main influential factor on content uniformity (CU). Additionally the influence of multiple feeders had a significant impact on CU. The results demonstrate that in-line NIR measurements is a powerful tool for process development (e.g., mixing characterization), monitoring and further control strategies. PMID:23911343

  14. Substrate and chain length dependencies of the thermal behavior of [CF3(CF2)m(CH2)nCOO]2Cd single monolayers investigated by infrared reflection absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Ren, Yanzhi; Asanuma, Morito; Iimura, Ken-ichi; Kato, Teiji

    2001-01-01

    Temperature-variable grazing incidence reflection absorption (GIR) spectra were recorded for the single monolayer of [CF3(CF2)m(CH2)nCOO)]2Cd [(m,n)=(7,10), (7,16), (7,22), (5,22), and (3,22)], transferred from aqueous Cd2+ subphase to gold- and aluminum-evaporated glass substrates. The spectra reveal that these monolayers have better thermal stability on Al substrates than on Au. An "interaction band" is identified at 1484˜1480 cm-1, due to the νs(COO-) mode of carboxylate headgroups in ionic bonding with the Al surface. It is found that both the van der Waals interaction between the trans zig-zag hydrocarbon chains and the overlapping interaction between the fluorocarbon helixes are responsible for the systematic variation of the monolayer thermal behavior with (m,n). The thermal behavior of a single monolayer of cadmium stearate, serving as a model system, has been investigated to further confirm the spectral interpretation about the partially fluorinated monolayer. In addition, temperature-dependent friction measurements show that the single monolayers of (m,n)=(7,16), (7,22), (5,22), and (3,22) are potential molecular lubricants that can be used in the range of 25˜140 °C.

  15. Organophosphate Hydrolase Is a Lipoprotein and Interacts with Pi-specific Transport System to Facilitate Growth of Brevundimonas diminuta Using OP Insecticide as Source of Phosphate.

    PubMed

    Parthasarathy, Sunil; Parapatla, Hari; Nandavaram, Aparna; Palmer, Tracy; Siddavattam, Dayananda

    2016-04-01

    Organophosphate hydrolase (OPH), encoded by the organophosphate degradation (opd) island, hydrolyzes the triester bond found in a variety of organophosphate insecticides and nerve agents. OPH is targeted to the inner membrane ofBrevundimonas diminutain a pre-folded conformation by thetwinargininetransport (Tat) pathway. The OPH signal peptide contains an invariant cysteine residue at the junction of the signal peptidase (Spase) cleavage site along with a well conserved lipobox motif. Treatment of cells producing native OPH with the signal peptidase II inhibitor globomycin resulted in accumulation of most of the pre-OPH in the cytoplasm with negligible processed OPH detected in the membrane. Substitution of the conserved lipobox cysteine to serine resulted in release of OPH into the periplasm, confirming that OPH is a lipoprotein. Analysis of purified OPH revealed that it was modified with the fatty acids palmitate and stearate. Membrane-bound OPH was shown to interact with the outer membrane efflux protein TolC and with PstS, the periplasmic component of the ABC transporter complex (PstSACB) involved in phosphate transport. Interaction of OPH with PstS appears to facilitate transport of Pigenerated from organophosphates due to the combined action of OPH and periplasmically located phosphatases. Consistent with this model,opdnull mutants ofB. diminutafailed to grow using the organophosphate insecticide methyl parathion as sole source of phosphate. PMID:26861877

  16. Transgenic oil palm: production and projection.

    PubMed

    Parveez, G K; Masri, M M; Zainal, A; Majid, N A; Yunus, A M; Fadilah, H H; Rasid, O; Cheah, S C

    2000-12-01

    Oil palm is an important economic crop for Malaysia. Genetic engineering could be applied to produce transgenic oil palms with high value-added fatty acids and novel products to ensure the sustainability of the palm oil industry. Establishment of a reliable transformation and regeneration system is essential for genetic engineering. Biolistic was initially chosen as the method for oil palm transformation as it has been the most successful method for monocotyledons to date. Optimization of physical and biological parameters, including testing of promoters and selective agents, was carried out as a prerequisite for stable transformation. This has resulted in the successful transfer of reporter genes into oil palm and the regeneration of transgenic oil palm, thus making it possible to improve the oil palm through genetic engineering. Besides application of the Biolistics method, studies on transformation mediated by Agrobacterium and utilization of the green fluorescent protein gene as a selectable marker gene have been initiated. Upon the development of a reliable transformation system, a number of useful targets are being projected for oil palm improvement. Among these targets are high-oleate and high-stearate oils, and the production of industrial feedstock such as biodegradable plastics. The efforts in oil palm genetic engineering are thus not targeted as commodity palm oil. Due to the long life cycle of the palm and the time taken to regenerate plants in tissue culture, it is envisaged that commercial planting of transgenic palms will not occur any earlier than the year 2020. PMID:11171275

  17. Ligand exchange in quaternary alloyed nanocrystals--a spectroscopic study.

    PubMed

    Gabka, Grzegorz; Bujak, Piotr; Giedyk, Kamila; Kotwica, Kamil; Ostrowski, Andrzej; Malinowska, Karolina; Lisowski, Wojciech; Sobczak, Janusz W; Pron, Adam

    2014-11-14

    Exchange of initial, predominantly stearate ligands for pyridine in the first step and butylamine (BA) or 11-mercaptoundecanoic acid (MUA) in the second one was studied for alloyed quaternary Cu-In-Zn-S nanocrystals. The NMR results enabled us to demonstrate, for the first time, direct binding of the pyridine labile ligand to the nanocrystal surface as evidenced by paramagnetic shifts of the three signals attributed to its protons to 7.58, 7.95 and 8.75 ppm. XPS investigations indicated, in turn, a significant change in the composition of the nanocrystal surface upon the exchange of initial ligands for pyridine, which being enriched in indium in the 'as prepared' form became enriched in zinc after pyridine binding. This finding indicated that the first step of ligand exchange had to involve the removal of the surface layer enriched in indium with simultaneous exposure of a new, zinc-enriched layer. In the second ligand exchange step (replacement of pyridine with BA or MUA) the changes in the nanocrystal surface compositions were much less significant. The presence of zinc in the nanocrystal surface layer turned out necessary for effective binding of pyridine as shown by a comparative study of ligand exchange in Cu-In-Zn-S, Ag-In-Zn-S and CuInS2, carried out by complementary XPS and NMR investigations. PMID:25252174

  18. Formulation and optimization of potassium iodide tablets.

    PubMed

    Al-Achi, Antoine; Patel, Binit

    2015-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light. PMID:25685048

  19. Synthesis of Saturated Long Chain Fatty Acids from Sodium Acetate-1-C14 by Mycoplasma1

    PubMed Central

    Pollack, J. D.; Tourtellotte, M. E.

    1967-01-01

    Three strains of Mycoplasma, M. laidlawii A and B, and Mycoplasma sp. A60549, were grown in broth containing sodium acetate-1-C14. The methyl esters of the phospholipid fatty acids of harvested radioactive cells were prepared and identified by comparison of their mobilities to known radioactive fatty acid methyl esters by use of a modified reversed-phase partition-thin layer chromatographic technique. No radioactive methyl oleate or methyl linoleate was detected. Compounds migrating as radioactive methyl myristate, stearate, palmitate, and, with less certainty, laurate and octanoate were detected. The qualitative findings for all three organisms appeared similar. M. laidlawii B synthesized a radioactive substance, presumably a saturated fatty acid detected as the methyl ester derivative, which migrated in a position intermediate to methyl myristate-1-C14 and methyl palmitate-1-C14. This work indicates that M. laidlawii A and B and Mycoplasma sp. A60549 are capable, in a complex medium containing fatty acids, of synthesizing saturated but not unsaturated fatty acids entirely or in part from acetate. Images PMID:6020566

  20. A surfactant-free recipe for shape-controlled synthesis of CdSe nanocrystals

    NASA Astrophysics Data System (ADS)

    Liu, Hongmei; Tao, Hong; Yang, Tingbin; Kong, Lingbin; Qin, Donghuan; Chen, Junwu

    2011-01-01

    We described surfactant-free recipes for the synthesis of CdSe nanocrystals (NCs) with well-controlled morphologies at a relatively low temperature. Dot-, rod-, tetrapod-and sphere-shaped CdSe NCs were prepared with trioctylphosphine oxide (TOPO) as a non-equilibrium solvent and trioctylphosphine selenide (TOPSe) and cadmium carboxylates as Se and Cd precursors, respectively. It was found that the morphology and stacking pattern of the CdSe NCs were related to the preparation conditions such as the concentration of the injected TOPSe(monomer concentration), reaction temperature and chain length of the cadmium carboxylate precursors. At a reaction temperature of 240 °C, CdSe NCs with a tetrapod selectivity of up to 85% were obtained in the presence of cadmium myristate under high concentrated TOPSe injection, and the in situ-formed myristic acid supplied the best acidic ligand with optimal amount to stabilize the anisotropic growth of the tetrapods. The intentional addition of more myristic acid in the reaction system would block the growth pathway of the tetrapods. Using cadmium laurate, cadmium palmitate and cadmium stearate as the cadmium precursors would reduce the formation of the tetrapods, showing the very low selectivity of the tetrapods.