Sample records for glyceryl trioleate

  1. Genetic control of macrophage functions. I. Polygenic regulation of phagocytosis stimulation produced by Glyceryl Trioleate.

    Mouton, D; Bouthillier, Y; Feingold, N; Feingold, J; Decreusefond, C; Stiffel, C; Biozzi, G


    The phagocytic index K, established from the rate of blood clearance of colloidal carbon, measures the phagocytic activity of RE macrophages in contact with the circulating blood. The intravenous injection of glyceryl trioleate (triolein) produces a marked stimulation of the phagocytic activity of RE macrophages. This response is higher in the female than in the male mice. The phenotypic character "responsiveness of macrophage to triolein" presents large individual variants in population of random bred albinos mice. This character is submitted to polygenic regulation. Starting from a foundation population of 25 males and 25 females random bred albinos, mice, two lines were separated by selective breeding for the character "responsiveness to triolein": a "high" responder line, KTH, and a "low" responder line, KTL. After 26 consecutive generations of selective breeding, KTH mice present a very high response to triolein while KTL mice are almost irresponsive. The heritability of this character (h2) calculated from the interline divergence is of 12% plus or minus 1. This value of h2 indicates that the character investigated is determined by the cumulative effect of a group of about 27 independently segregating loci. The distribution of the character in (KTH plus KTL)F1 and their backcrosses with parental lines suggests that low responsiveness is dominant over high responsiveness. The genetic regulation of responsiveness to triolein is independent from the dose administered. These results are discussed in relation to the importance of genetic factors controlling macrophage functions involved in lipid metabolism and in the specific mechanisms of immunity.

  2. Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate.


    The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed in a safety assessment completed in 2000. Additional safety test data pertaining to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served as the basis for this amended report. Glyceryl monoesters are used mostly as skin-conditioning agents--emollients and/or surfactant--emulsifying agents in cosmetics. The following 20 glyceryl monoesters are currently reported to be used in cosmetics: Glyceryl Laurate, Glyceryl Alginate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Cocoate, Glyceryl Erucate, Glyceryl Hydroxystearate, Glyceryl Isostearate, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Myristate, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Stearate/Acetate, and Glyceryl Undecylenate. Concentration of use data received from the cosmetics industry in 1999 indicate that Glyceryl Monoesters are used at concentrations up to 12% in cosmetic products. Glyceryl Monoesters are not pure monoesters, but are mostly mixtures with mono-, di-, and tri-esters. The purity of commercial and conventional Monoglyceride (Glyceryl Monoester) is a minimum of 90%. Glyceryl Monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides. Glyceryl Laurate enhanced the penetration of drugs through cadaverous skin and hairless rat skin in vitro and has been described as having a wide spectrum of antimicrobial activity. A low-grade irritant response was observed following inhalation of an aerosol containing 10% Glyceryl Laurate by test animals. Glyceryl monoesters have little acute or short-term toxicity in animals, and no toxicity was noted following chronic administration of a mixture consisting mostly of glyceryl di- and mono- esters. Glyceryl Laurate did have strong hemolytic

  3. Amended final report on the safety assessment of glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dierucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate, and glyceryl stearate succinate.


    Glyceryl Dilaurate, Glyceryl Diarachidate, Glyceryl Dibehenate, Glyceryl Dierucate, Glyceryl Dihydroxystearate, Glyceryl Diisopalmitate, Glyceryl Diisostearate, Glyceryl Dilinoleate, Glyceryl Dimyristate, Glyceryl Dioleate, Glyceryl Diricinoleate, Glyceryl Dipalmitate, Glyceryl Dipalmitoleate, Glyceryl Distearate, Glyceryl Palmitate Lactate, Glyceryl Stearate Citrate, Glyceryl Stearate Lactate, and Glyceryl Stearate Succinate are diacylglycerols (also known as diglycerides or glyceryl diesters) that function as skin conditioning agents - emollients in cosmetics. Only Glyceryl Dilaurate (up to 5%), Glyceryl Diisostearate (up to 43%), Glyceryl Dioleate (up to 2%), Glyceryl Distearate (up to 7%), and Glyceryl Stearate Lactate (up to 5%) are reported to be in current use. Production proceeds from fully refined vegetable oils, which are further processed using hydrogenation and fractionation techniques, and the end products are produced by reacting selected mixtures of the partly hydrogenated, partly fractionated oils and fats with vegetable-derived glycerine to yield partial glycerides. In the final stage of the production process, the products are purified by deodorization, which effectively removes pesticide residues and lower boiling residues such as residues of halogenated solvents and aromatic solvents. Diglycerides have been approved by the Food and Drug Administration (FDA) for use as indirect food additives. Nominally, these ingredients are 1,3-diglycerides, but are easily isomerized to the 1,2-diglycerides form. The 1,3-diglyceride isomer is not a significant toxicant in acute, short-term, subchronic, or chronic animal tests. Glyceryl Dilaurate was a mild primary irritant in albino rabbits, but not a skin sensitizer in guinea pig maximization tests. Diacylglycerol Oil was not genotoxic in the Ames test, in mammalian Chinese hamster lung cells, or in a rodent bone marrow micronucleus assay. An eye shadow containing 1.5% Glyceryl Dilaurate did not induce skin

  4. Synthesis and physicochemical properties of epoxidized Tmp trioleate by in situ method

    Samidin, Salma; Salimon, Jumat [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor (Malaysia)


    Tmp trioleate was initially synthesized via esterification of trimetilolprapane and oleic acid (90%) using 1.5% of H{sub 2}SO{sub 4} as a catalyst. The production of Tmp trioleate was observed at 98% (w/w). The iodine value of Tmp trioleate was analyzed for further reaction of epoxidation. Epoxide was important reaction as an intermediate for preparation of chemical modified lubricants from vegetable oils. Finding the best way of epoxidation process will give high quality for further modification of oil instead of reduce the cost and time for the preparation process during reaction of epoxidation. In this study, the epoxidation of unsaturation Tmp trioleate with peroxyformic acid generated in-situ from hydrogen peroxide 30% in H{sub 2}O{sub 2} with formic acid was studied. 95% conversion to oxygen oxirane content (OOC) ring was obtained. The derivatization showed an improvement of the compound's oxidative stability evidenced from pressurized differential scanning calorimetry (PDSC) data which are 177°C to 200°C. Physicochemical properties showed increasing of temperature of flash point from 280°C to 300°C and viscosity index (VI) from 146 to 154. However, the pour point showed increasing temperature which was −58.81°C to −17.32°C. From the data obtained, these derivatives have shown better performance of lubricity properties. Overall, the data indicates that these performances are compatible to the commercial lubricants.

  5. Gallbladder emptying and cholecystokinin response to fish oil and trioleate ingestion

    Riber, C; Hojgaard, L; Madsen, J L


    The aim of the present study was to compare gallbladder emptying, gastric emptying and release of cholecystokinin (CCK), gastrin and secretin after intragastric administration of fish oil and trioleate. After intravenous injection of 99mTc-HIDA, 30 ml of a lipid labelled with 111In was administer...

  6. Glyceryl guaiacol ether – review

    Massone, Flávio; Universidade Estadual Paulista; Luna, Stélio Pacca Loureiro; Universidade Estadual Paulista; Castro, Gladys Bastos; Universidade Estadual Paulista


    The history, physical and chemical properties, pharmacodynamics, pharmacokinetics, adverse effects, toxicity, clinical use in wild and domestic species and drug interactions with glyceryl guaiacol ether, an a-glyceryt ether, is presented. Guaiphenesin produces muscle relaxation without affecting diaphragmatic function. Besides muscle relaxation, the drug produces hypocholesterolemia, hypouricemia and has antitussive and expectorant actions, among others. It is a safe agent, but can produce th...

  7. 21 CFR 184.1328 - Glyceryl behenate.


    ... glyceryl esters of behenic acid made from glycerin and behenic acid (a saturated C22 fatty acid). The... not more than 2.5 percent free fatty acids. (2) Behenic acid. Between 80 and 90 percent of the total fatty acid content. (3) Acid value. Not more than 4. (4) Saponification value. Between 145 and 165....

  8. 21 CFR 184.1324 - Glyceryl monostearate.


    ... esters of fatty acids present in commercial stearic acid. Glyceryl monostearate is prepared by... FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE..., of stearic acid that is derived from edible sources. (b) The ingredient must be of a purity...

  9. 21 CFR 184.1323 - Glyceryl monooleate.


    ... esterification of commerical oleic acid that is derived either from edible sources or from tall oil fatty acids.... No. 25496-72-4) and glyceryl esters of fatty acids present in commercial oleic acid. (b) The... HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing...

  10. Mechanisms of glyceryl trinitrate provoked mast cell degranulation

    Pedersen, Sara Hougaard; Ramachandran, Roshni; Amrutkar, Dipak Vasantrao;


    inflammation and dural mast cell degranulation is supported by the effectiveness of prednisolone on glyceryl trinitrate-induced delayed headache. METHODS: Using a newly developed rat model mimicking the human glyceryl trinitrate headache model, we have investigated the occurrence of dural mast cell...... glyceryl trinitrate-induced mast cell degranulation whereas the calcitonin gene-related peptide-receptor antagonist olcegepant and the substance P receptor antagonist L-733,060 did not affect mast cell degranulation. However, topical application of two different nitric oxide donors did not cause mast cell...... degranulation ex vivo. CONCLUSIONS: Direct application of an exogenous nitric oxide donor on dural mast cells does not cause mast cell degranulation ex vivo. In vivo application of the nitric oxide donor glyceryl trinitrate leads to a prominent level of degranulation via a yet unknown mechanism. This effect can...

  11. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.


    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glyceryl-lacto esters of fatty acids. 172.852... HUMAN CONSUMPTION Multipurpose Additives § 172.852 Glyceryl-lacto esters of fatty acids. Glyceryl-lacto esters of fatty acids (the lactic acid esters of mono- and diglycerides) may be safely used in food in...

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


    ... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3505 Glyceryl tri-(12-acetoxy-stearate). Glyceryl tri-(12-acetoxystearate) (CAS Reg. No. 139-43-5) may be safely used as a component of articles...

  13. A naturalistic glyceryl trinitrate infusion migraine model in the rat

    Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri


    Glyceryl trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine...... is not certain. Anaesthesia and low blood pressure caused by high GTN doses both can affect the expression of nociceptive marker c-fos. Therefore, our aim was to simulate the human GTN migraine model in awake rats using a clinically relevant dose....

  14. Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence.

    Watschinger, Katrin; Keller, Markus A; Hermetter, Albin; Golderer, Georg; Werner-Felmayer, Gabriele; Werner, Ernst R


    Glyceryl ether monooxygenase is a tetrahydrobiopterin-dependent membrane-bound enzyme which catalyses the cleavage of lipid ethers into glycerol and the corresponding aldehyde. Despite many different characterisation and purification attempts, so far no gene and primary sequence have been assigned to this enzyme. The seven other tetrahydrobiopterin-dependent enzymes can be divided in the family of aromatic amino acid hydroxylases - comprising phenylalanine hydroxylase, tyrosine hydroxylase and the two tryptophan hydroxylases - and into the three nitric oxide synthases. We tested the influences of different metal ions and metal ion chelators on glyceryl ether monooxygenase, phenylalanine hydroxylase and nitric oxide synthase activity to elucidate the relationship of glyceryl ether monooxygenase to these two families. 1,10-Phenanthroline, an inhibitor of non-heme iron-dependent enzymes, was able to potently block glyceryl ether monooxygenase as well as phenylalanine hydroxylase, but had no effect on inducible nitric oxide synthase. Two tetrahydrobiopterin analogues, N(5)-methyltetrahydrobiopterin and 4-aminotetrahydrobiopterin, had a similar impact on glyceryl ether monooxygenase activity, as has already been shown for phenylalanine hydroxylase. These observations point to a close analogy of the role of tetrahydrobiopterin in glyceryl ether monooxygenase and in aromatic amino acid hydroxylases and suggest that glyceryl ether monooxygenase may require a non-heme iron for catalysis.

  15. Glyceryl trinitrate patches—An alternative treatment for shoulder impingement syndrome

    Yusuf Assem


    Full Text Available Transdermal glyceryl trinitrate patches have been investigated as an alternative therapeutic intervention for a range of tendinopathies, due to the ease of titration of dosage and the ease of their application. Glyceryl trinitrate has been inferred to reduce pain and inflammation secondary to their nitric oxide-producing action. Shoulder impingement syndrome is a soft tissue condition that manifests as anterior shoulder pain, weakness, and difficulty in daily activities. This review will evaluate the efficacy of glyceryl trinitrate patches in treating a variety of rotator cuff tendinopathies related to shoulder impingement, based on human and animal trials, and suggest its practical application in future trials and management.

  16. Intracranial hemodynamics during intravenous infusion of glyceryl trinitrate

    Iversen, H.K.; Holm, S.; Friberg, L.;


    The mechanisms of glyceryl trinitrate (GTN)-induced headache are not fully elucidated. In this study we administered GTN 0.5 microg/kg/min i.v. for 20 min in six healthy volunteers. Before, during and 60 min after the infusion, we investigated regional cerebral blood flow (rCBF), cerebral blood...... volume (CBV), both estimated with SPECT, and blood flow velocity (BFV) in the middle cerebral artery (MCA), measured with transcranial Doppler. Headache was scored on a numerical verbal rating (0-10) scale. rCBF was unchanged, CBV was slightly increased (13%) during GTN infusion, whereas BFV decreased...... both during (20%) and 60 min (15%) after GTN. Headache was short-lived and maximal during infusion. This discrepancy of time-effect curves for the effect of GTN on headache and dilatation of MCA indicates that MCA is most likely not the primary source of pain in GTN-induced headache. The time...

  17. States of Water in Hydrogels Containing with Glyceryl Methacrylate

    LI Qin-hua; LIU Li; HUANG Zhi-rong; LIN Dong-qing


    Hydrogel materials were prepared by thermopolymerization with different content of glyceryl methacrylate and hydroxyethyl methacrylate. The different states of water in swelling hydrogels were described and studied by differential scanning calorimetry (DSC). It was found that the hydrophilicity of GMA was stronger than HEMA, the water content and bound water of GMA hydrogel are higher than HEMA hydrogel. With the increase of GMA content, the content of free water in hydrogel increased. When GMA content was lower than 50%, the increase of GMA content also increased the content of bound water; but when GMA content was higher than 50%, the increase of GMA content decreased the content of bound water, which was caused by the chain hydrogen bond formed on the GMA chain with hydroxyl group each other.

  18. Clinical value of dual-isotope fat absorption test system (FATS) using glycerol (/sup 125/I)trioleate and glycerol (/sup 75/Se)triether

    Lembcke, B.; Loesler, A.C.; Caspary, W.F.; Schuernbrand, P.E.; Emrich, D.; Creutzfeldt, W.


    In order to delineate the clinical value of a dual-isotope fat absorption test system (FATS) using glycerol (/sup 75/Se)triether as lipid-phase marker and glycerol (/sup 125/I)trioleate as the test lipid, fecal isotope ratios from single stools (and a 72-hr stool homogenate) were compared to quantitative fecal fat excretion. The study included 11 patients without and 24 patients with steatorrhea. With a figure of 0.8% as the upper limit of normal, the test was a reliable indicator of steatorrhea with 87.5% sensitivity and 81.8% specificity; efficiency was 85.7%. Related to a prevalence of steatorrhea of 45.9% as the mean value of 1269 consecutive 72-hr specimens investigated for steatorrhea during 1978-1982, the positive (negative) predictive value of the FATS is 80.3% (87.2%). With 2% as the upper limit of normal, no false positive results ensued. It is concluded that a two-step interpretation of the FATS (0.8% limit and 2% limit) may be regarded a valid qualitative index for steatorrhea. The FATS isotope ratio using single stools correlated well with FATS ratios in the 72-hr stool homogenates (r = 0.97). FATS therefore allows a convenient estimate of steatorrhea from measuring single stools. As a quantitative measure of fecal fat excretion, the FATS is unreliable.

  19. Preparation and optimization of glyceryl behenate-based highly porous pellets containing cilostazol.

    Hwang, Kyu-Mok; Byun, Woojin; Cho, Cheol-Hee; Park, Eun-Seok


    The aim of this study was to prepare a highly porous multiparticulate dosage form containing cilostazol for gastroretentive drug delivery. The floating pellets were prepared with glyceryl behenate as a matrix former and camphor as a sublimating agent by extrusion/spheronization and sublimation under vacuum. Granules prepared with sublimation at 60 °C displayed a slower dissolution rate and smoother surface morphology than those prepared at lower temperatures. This was unexpected as the reported melting point of glyceryl behenate is higher than 69 °C. The DSC study revealed that melting began at a lower temperature owing to the multicomponent property of glyceryl behenate, which led to a sintering effect. The prepared pellets were spherical with unimodal size distribution. They also had porous structures with increased porosity, which led to immediate buoyancy. As cilostazol is a hydrophobic drug that has an erosion-based release mechanism, drug release profile was highly correlated with the percentage of disintegrated pellets. Various excipients were added to the glyceryl behenate-based formulation to increase the floating duration. When hydroxyethyl cellulose was added to the glyceryl behenate-based pellets, acceptable dissolution rate and buoyancy were acquired. This system could potentially be used for gastroretentive delivery of various hydrophobic drugs, which was generally considered difficult.

  20. Compressibility of tableting materials and properties of tablets with glyceryl behenate

    Mužíková Jitka


    Full Text Available The paper studies the compressibility of directly compressible tableting materials with dry binders, spray-dried lactose and microcrystalline cellulose, and glyceryl dibehenate at various concentrations. Compressibility was evaluated by means of the energy profile of compression and tensile strength of tablets. Release rate of the active ingredient, salicylic acid, from the tablets was also examined. In the case of microcrystalline cellulose, a higher concentration of glyceryl dibehenate increased the strength of tablets, while this did not occur in the case of spray-dried lactose. Increasing concentration of glyceryl dibehenate prolonged the release of salicylic acid; however, no statistically significant difference was found compared to the type of the dry binder used

  1. Determination of optimum processing temperature for transformation of glyceryl monostearate.

    Yajima, Toshio; Itai, Shigeru; Takeuchi, Hirofumi; Kawashima, Yoshiaki


    The purpose of this study was to clarify the mechanism of transformation from alpha-form to beta-form via beta'-form of glyceryl monostearate (GM) and to determine the optimum conditions of heat-treatment for physically stabilizing GM in a pharmaceutical formulation. Thermal analysis repeated twice using a differential scanning calorimeter (DSC) were performed on mixtures of two crystal forms. In the first run (enthalpy of melting: DeltaH1), two endothermic peaks of alpha-form and beta-form were observed. However, in the second run (enthalpy of melting: DeltaH2), only the endothermic peak of the alpha-form was observed. From a strong correlation observed between the beta-form content in the mixture of alpha-form and beta-form and the enthalpy change, (DeltaH1-DeltaH2)/DeltaH2, beta-form content was expressed as a function of the enthalpy change. Using this relation, the stable beta-form content during the heat-treatment could be determined, and the maximum beta-form content was obtained when the heat-treatment was carried out at 50 degrees C. An inflection point existed in the time course of transformation of alpha-form to beta-form. It was assumed that almost all of alpha-form transformed to beta'-form at this point, and that subsequently only transformation from beta'-form to beta-form occurred. Based on this aspect, the transformation rate equations were derived as consecutive reaction. Experimental data coincided well with the theoretical curve. In conclusion, GM was transformed in the consecutive reaction, and 50 degrees C was the optimum heat-treatment temperature for transforming GM from the alpha-form to the stable beta-form.

  2. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J


    : To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...... of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

  3. CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine

    Tvedskov, Jesper Filtenborg; Tfelt-Hansen, P; Petersen, K A;


    There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN.......There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN....

  4. Hemodynamic effect of avanafil and glyceryl trinitrate coadministration

    Dennis Swearingen


    Full Text Available A Phase I, double-blind, randomized, crossover study in healthy males (N=106 was conducted between March 21, 2004, and May 17, 2004, to determine the magnitude and duration of the hemodynamic interaction of avanafil (a phosphodiesterase type-5 inhibitor for treating males with erectile dysfunction when coadministered with glyceryl trinitrate (NTG compared with sildenafil and placebo. Subjects received avanafil (200 mg, sildenafil (100 mg, and placebo (on separate days via the oral route followed by NTG (0.4 mg 12, 8, 4, 1, or 0.5 hours post-dose via the sublingual route. Blood pressure (BP and heart rate (HR were assessed at defined intervals.Throughout the study (after administration of the study drug, and including the period after NTG administration, the effects of avanafil and sildenafil on BP and HR were significantly greatest overall, at the shortest (0.5-hour time interval compared with placebo. By the 8- and 12-hour time intervals, no significant difference in BP or HR was observed for avanafil (8 and 12 hours or sildenafil (12 hours (p>0.05, compared with placebo. Compared with avanafil, sildenafil had a significantly greater effect when dosed 0.5 hours before NTG on standing HR (p=0.05; 1 hour before NTG on standing systolic blood pressure (SBP (p<0.05, sitting SBP (p=0.01 and standing HR (p<0.01; and 12 hours before NTG on standing SBP (p=0.05. Throughout the study, symptomatic hypotension adverse events occurred in 27%, 29%, and 12%, and clinically significant reductions in standing SBP (≥30 mmHg occurred in 15%, 29%, and 12% of subjects dosed with avanafil, sildenafil, and placebo, respectively (overall treatment differences: p<0.01 and p<0.05,respectively.These data show that avanafil and sildenafil have no significant effect on BP and HR if administered to healthy males ≥8 hours (avanafil or ≥12 hours (sildenafil before a sublingual dose of NTG. However, results may differ in populations with known vascular disease

  5. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon;


    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how...

  6. Oral 2-oleyl glyceryl ether improves glucose tolerance in mice through the GPR119 receptor

    Hassing, H A; Engelstoft, M S; Sichlau, R M


    abolished the hormone release. Similarly, in isolated primary colonic crypt cultures from WT mice, GPR119 was required for 2-OG-stimulated GLP-1 release while there was no response in crypts from KO mice. In vivo, gavage with 2-oleyl glyceryl ether ((2-OG ether), a stable 2-OG analog with a potency of 5.3 µ...

  7. No effect of pure oxygen inhalation on headache induced by glyceryl trinitrate

    Daugaard, D.; Tfelt-Hansen, P.; Thomsen, L.L.


    Inhalation of hyperbaric oxygen has been used as an experimental treatment for migraine and pure oxygen is an established treatment for cluster headache. Intravenous glyceryl trinitrate (GTN) is an established headache model. In the present study the possibility of decreasing the headache...

  8. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon;


    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how pharm...... pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal....

  9. Ceratodictyols, 1-Glyceryl Ethers from the Red Alga-Sponge Association Ceratodictyon spongiosum/Haliclona cymaeformis

    Akiyama, T.; Ueoka, R.; van Soest, R.W.M.; Matsunaga, S.


    Six 1-glyceryl ethers (1−6) were isolated from the red alga−sponge assemblage Ceratodictyon spongiosum/Haliclona cymaeformis. Structural assignments were conducted by interpretation of spectroscopic data and the modified Mosher’s method. Four allylic alcohols were obtained as a pair of epimeric




    Full Text Available BACKGROUND: Preterm labour is onset of labour between 20 weeks and 37 completed weeks of gestation. Tocolytics are pharmacological agents that relax the uterine myometrium and inhibit uterine contractions leading to abolition of preterm labour. Many tocolytic drugs have been developed and used and several experimental drugs are being evaluated. Future research is needed for development of drugs with more utero - selectivity and fewer side effects. Ritodrine hydrochloride is now considered one of the most effective tocolytic drug . However, the use of nitroglycerine patch has shown comparable results and there is a need for further critical evaluation by well - planned and well monitored studies. AIM: To compare the efficacy of transdermal glyceryl trinitrate and intravenous ritodrin e as tocolytics. MATERIAL AND METHODS: The study was conducted on patients who attended Bapuji Hospital , Chigateri Hospital and women and child hospital, attached to J .J.M . Medical College, Davangere. One hundred patients who were admitted and clinically di agnosed with preterm labour were randomised either to group 1, treated with glyceryl trinitrate patch or group II, treated with ritodrine, with fifty patients in each group. ANALYSIS: Descriptive data that included mean, Standard deviation, percentages wer e determined and presented for each group. Difference between two groups was compared by Mann - Whitney test for continuous data and chi - square test for categorical data. P Valve of 0.05 or less was considered for statistical significance. RESULTS: mean per centage prolongation of gestation with glyceryl trinitrate was 58±45.9 and with Ritodrine , it was 62±44.6. Mean absolute prolongation of gestation with glyceryl trinitrate was 3.22 weeks and with Ritodrine it was 3.18 weeks. CONCLUSION: Both glyceryl trini trate and ritodrine were comparable in prolongation of gestation in patients in preterm labour, both in duration and in terms of success. The

  11. Biocompatible microemulsions for fabrication of glyceryl monostearate solid lipid nanoparticles (SLN) of tretinoin.

    Shah, Kumar A; Joshi, Medha D; Patravale, Vandana B


    The objective of the present investigation was to fabricate glyceryl monostearate SLN by employing a biocompatible microemulsion as a template. Biocompatible excipients such as Tween 20 (as a surfactant) and Transcutol P (a cosourfactant) (at different K(m) ratios) were selected for the fabrication of microemulsions. Pseudo-ternary phase diagrams were plotted to identify the area of the microemulsion existence. Glyceryl monostearate SLN were fabricated by dispersing the microemulsion (maintained at 65 degrees C) into cold water (maintained at 2-3 degrees C). The particle size of the SLN was determined by photon correlation spectroscopy. Tretinoin, a lipophilic anti-acne agent was incorporated into SLN as a model drug. The encapsulation efficiency of tretinoin in the SLN was determined by using Nanosep ultrafilteration device at different lipid loads viz. 1%, 1.5% and 2%. Glyceryl monostearate SLN fabricated from biocompatible microemulsion template exhibited average particle size of 175 nm and polydispersity index of 0.833. Tretinoin could be successfully incorporated into SLN and the encapsulation efficiency ranged from 37-48% at different lipid loads.

  12. Novel glyceryl glucoside is a low toxic alternative for cryopreservation agent

    Su, Cathy; Allum, Allison J. [Department of Environmental & Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523 (United States); Aizawa, Yasushi [Research and Development Group, Toyo Sugar Refining Co. Ltd., Tokyo 103-0046 (Japan); Kato, Takamitsu A., E-mail: [Department of Environmental & Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523 (United States)


    Glyceryl glucoside (GG, α-D-glucosyglycerol) is a natural glycerol derivative found in alcoholic drinks. Recently GG has been used as an alternative for glycerol in cosmetic products. However, the safety of using GG is still unclear. Currently, dimethyl sulfoxide (DMSO) and glycerol are wildly used in cryopreservation. Despite GG being a derivative of glycerol, the ability of GG in cryopreservation is still unknown. By using a system of Chinese Hamster Ovary cells (CHO), A549 cells and AG1522 cells, the study examined the cryoprotective effects of DMSO, glycerol and GG. Cytotoxic and genotoxic responses induced by the three chemicals were also investigated with CHO to determine the safety of GG for cosmetic products. Our data suggests that GG has great cryopresearvation ability in the concentration of 30%–40% (v/v). For cytotoxic studies, DMSO showed the highest cytotoxicity above 3% (v/v) in cell doubling time delay among three chemicals. For the acute cytotoxicity with trypan blue dye exclusion assay, GG showed stronger cell killing effect within 24 h above 4% (v/v). For the continuous cytotoxicity with colony formation assay for 7 days, DMSO showed significantly reduced clonogenic ability above 2%. In genotoxicity studies, CHO treated with glycerol at 2% concentration induced three times higher frequencies of sister chromatid exchange (SCE) than background levels. GG did not induce significant amounts of SCE compared to background. Micronuclei formation was equally observed in the 2% and above concentrations of glycerol and GG. Our data showed that GG has significant effects on cryopreservation compared to DMSO. Glycerol and GG have similar cytotoxicity effects to CHO, but glycerol induced genotoxic responses in the same concentration. Therefore, we conclude that GG may be a safer alternative compound to glycerol in cosmetic products and safer alternative to DMSO in cryopreservation. -- Highlights: •Glyceryl Glucoside is low cytotoxicity and genotoxicity

  13. Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis: A randomized placebo-controlled trial

    Jian-Yu Hao; Dong-Fang Wu; Yue-Zeng Wang; Ying-Xin Gao; Hai-Po Lang; Wei-Zhen Zhou


    AIM: To examine the prophy lacticef fect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasemia.METHODS: Patients scheduled for ERCP were randomly divided into study group and placebo group. Patients in study group and placebo group were treated with 5 mg glyceryl trinitrate and 100 mg vitamin C, respectively, 5 min before endoscopic maneuvers.RESULTS: A total of 74 patients were enrolled in the final analysis. Post-ERCP pancreatitis occurred in 3 patients (7.9%) of the study group and 9 patients (25%) in the placebo group ( P = 0.012).Hyperamylasemia occurred in 8 patients of the study group (21.1%) and 13 patients (36.1%) of the placebo group ( P = 0.037).CONCLUSION: Glyceryl trinitrate before ERCP can effectively prevent post-ERCP and hyperamylasemia.

  14. RNA sequencing of trigeminal ganglia in Rattus Norvegicus after glyceryl trinitrate infusion with relevance to migraine

    Pedersen, Sara Hougaard; Sørensen, Lasse Maretty; Ramachandran, Roshni


    transcriptional responses to GTN-infusion in the rat trigeminal ganglia. METHODS: Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed......INTRODUCTION: Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate...

  15. Influence of glyceryl guaiacolate ether on anesthetics in tilapia compared to benzocaine and eugenol

    Geovana R. Cosenza


    Full Text Available Objective. The study aimed to investigate the effectiveness of glyceryl guaiacolate ether (GGE and compare the times of induction, recovery, hematological changes, total protein and glycaemia among anesthetics in Nile tilapia, Oreochromis niloticus. Materials and methods. A total of 60 tilapia distributed in 3 aquariums (N=20 were used, which formed the group benzocaine (100 mg/L, eugenol (50 mg/L and guaiacol glyceryl ether (9.000 mg/L. After the induction of anesthesia fish blood samples were collected to determine the complete hemogram and glycemia. Then the animals were placed in aquariums with running water for assessing the anesthesia recovery. Results. It was verified that GGE showed longer induction and recovery times as well a significant increase (p0.05. An increase in the number of monocytes in the group treated with benzocaine (p <0.05 was observed in the analysis of the hematological parameters with no difference between groups for other variables. Conclusions. Eugenol and benzocaine allow rapid induction and recovery in Nile tilapia, without evidence of stress during handling and GGE showed high induction and recovery times, being inadequate for anesthetic use in Nile tilapia.

  16. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy : a randomised, double-blind, placebo-controlled clinical trial

    Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam


    Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN

  17. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy : a randomised, double-blind, placebo-controlled clinical trial

    Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

    Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN

  18. CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine

    Tvedskov, J F; Tfelt-Hansen, P; Petersen, K A


    and in nine of 13 with placebo (p=0.68). The headache scores were similar after the two treatments (p=0.58). Thus CGRP receptor blockade did not prevent GTN-induced migraine. CONCLUSIONS: The present study indicates that NO does not induce migraine by liberating CGRP. The most likely explanation for our......UNLABELLED: There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN. METHODS......: In a double-blind-cross-over study, 13 migraine without aura (MO) patients were administered GTN 0.5 µg/kg/minute for 20 minutes and subsequently BIBN4096BS (olcegepant) 10 mg or placebo. Headache scores and development of MO were followed for 24 hours. RESULTS: MO developed in seven of 13 with olcegepant...

  19. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    Hougaard Pedersen, Sara; Maretty, Lasse; Ramachandran, Roshni;


    INTRODUCTION: Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate...... transcriptional responses to GTN-infusion in the rat trigeminal ganglia. METHODS: Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed...... a novel method for Gene Set Analysis Of Variance (GSANOVA) to identify gene sets associated with transcriptional changes across time. RESULTS: 15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down...

  20. Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

    Daugaard, D.; Thomsen, L. L.; Iversen, H. K.;


    Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate...... cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14...... healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 mu g kg-1 min-1 for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity...

  1. No effect of pure oxygen inhalation on headache induced by glyceryl trinitrate

    Daugaard, D.; Tfelt-Hansen, P.; Thomsen, L.L.


    Inhalation of hyperbaric oxygen has been used as an experimental treatment for migraine and pure oxygen is an established treatment for cluster headache. Intravenous glyceryl trinitrate (GTN) is an established headache model. In the present study the possibility of decreasing the headache...... by inhalation of pure oxygen was explored in a double-blind crossover design in 18 healthy subjects. Inhalation of air served as placebo. The subjects received intravenous GTN (0.25 A mu g/kg/min) for 20 min. Headache was scored for 85 min. Sixteen of 18 (89%) subjects experienced GTN-induced headache after O-2......-inhalation and 17/18 (94%) experienced GTN-induced headache after air. The mean peak headache scores were 1.9 and 2.4, respectively, on a numerical scale of 0-10. Oxygen inhalation did not have effect on GTN-induced headache, most likely because the theoretical decrease in NO levels, due to faster metabolism...

  2. Transdermal glyceryl trinitrate (nitroglycerin in healthy persons: acute effects on skin temperature and hemodynamic orthostatic response

    Eva Maria Augusta Boeckh Haebisch

    Full Text Available In order to find an explanation for individual reactions to transdermal glyceryl trinitrate (GTN we studied the skin temperature and hemodynamic reactions in 63 healthy persons. The data were obtained before and after the application of GTN and Glycerin (GL placebo patches, during one hour. The skin temperature was measured on both forearms, the local (left sided and systemic (right sided reaction on GTN was related to the skin fold and the calculated body fat content. The bilateral rise of skin temperature and its duration was higher and longer in obese than in lean persons mainly in obese women. The UV induced thermo and the later photothermoreaction (Erythema was reduced on the left forearm after the application of GTN and GL patches. The observed hemodynamic GTN effect confirmed known postural reactions, such as decreased arterial pressure (ΔmAP = -2.9%, increased heart rate (ΔHR = +7,4% and QTc prolongation (ΔQTc = +4,9% in upright position. An adverse drug effect with increased mean blood pressure (ΔmAP = +12% and increased heart rate (ΔHR = + 10.4% mainly in supine position was observed in 11 % of the participants, but only in men. Such a reaction was already described by Murell, 1879. Individual GTN effects were analyzed and related to habits and family history. In male smokers and in persons with hypertensive and diabetic close relatives, the hypotensive GTN effect was accentuated in supine position. In the upright position the group with hypertensives in the family presented a moderate hypotensive reaction without secondary tachycardia and the smokers presented only a slightly increased heart rate. Our observations suggest that individual reactions to transdermal glyceryl trinitrate (GTN with its active component nitric oxide (NO depends on physiological conditions, related to endogenous vasoactive substances, mainly the interaction with EDRF (the endogenous NO and the activity of the Renin-Angiotensin System.

  3. Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: Rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053).

    Appleton, Jason P; Scutt, Polly; Dixon, Mark; Howard, Harriet; Haywood, Lee; Havard, Diane; Hepburn, Trish; England, Tim; Sprigg, Nikola; Woodhouse, Lisa J; Wardlaw, Joanna M; Montgomery, Alan A; Pocock, Stuart; Bath, Philip M


    Rationale Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim To test the safety and efficacy of four days of transdermal glyceryl trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (glyceryl trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (≤4 h of onset) FAST-positive presumed stroke and systolic blood pressure ≥120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status Trial is ongoing. Funding British Heart Foundation. Registration ISRCTN26986053.

  4. Rheology of oleogels based on sorbitan and glyceryl monostearates and vegetable oils for lubricating applications

    Sánchez, R.


    Full Text Available Oleogels based on sorbitan and glyceryl monostearates and different types of vegetable oils, potentially applicable as biodegradable alternatives to traditional lubricating greases, have been studied. In particular, the rheological behavior, by means of small-amplitude oscillatory shear (SAOS measurements, and some lubrication performance-related properties (mechanical stability and tribological response have been evaluated in this work. SAOS response and mechanical stability of these oleogels are significantly influenced by the type and concentration of the organogelator and the vegetable oil used in the formulations. Glyceryl monostearate (GMS generally produces stronger gels than sorbitan monostearate (SMS. The use of low-viscosity oils, such as rapeseed and soybean oils, yields gels with significantly higher values of the linear viscoelastic functions than oleogels prepared with high-viscosity oils, i.e. castor oil. The rheological behavior of SMS-based oleogels also depends on the cooling rate applied during the gelification process. On the other hand, the oleogels studied present low values of the friction coefficient obtained in a tribological contact, although only some GMS/castor oil-based oleogels exhibit a suitable mechanical stability.

    En el presente trabajo se han estudiado diferentes oleogeles, basados en monoestearatos de sorbitano y glicerilo y aceites vegetales, que podrían ser potencialmente empleados como alternativas biodegradables a las grasas lubricantes tradicionales. En concreto, se ha evaluado su comportamiento reológico, a través de ensayos en cizalla oscilatoria, y algunas propiedades relacionadas con su rendimiento en la lubricación, tales como su estabilidad mecánica y comportamiento tribológico. La respuesta reológica y la estabilidad mecánica de los oleogeles estudiados están significativamente influenciadas por el tipo y la concentración del agente gelificante y por el aceite vegetal empleado. As

  5. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine.

    Sara Hougaard Pedersen

    Full Text Available Infusion of glyceryl trinitrate (GTN, a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate transcriptional responses to GTN-infusion in the rat trigeminal ganglia.Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed a novel method for Gene Set Analysis Of Variance (GSANOVA to identify gene sets associated with transcriptional changes across time.15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down-regulation in the 90-minute period after infusion. The GSANOVA analysis demonstrate enrichment of pathways pointing towards an increase in immune response, signal transduction, and neuroplasticity in response to GTN-infusion. Future functional in-depth studies of these mechanisms are expected to increase our understanding of migraine pathogenesis.

  6. Steady-state maternal and fetal plasma concentrations of glyceryl trinitrate (GTN) in the preterm sheep.

    Bustard, Mark A; Farley, Anne E; Bennett, Brian M; Smith, Graeme N


    The administration of glyceryl trinitrate (GTN; nitroglycerin) is increasing during preterm pregnancies, yet its disposition and, importantly, the extent of fetal exposure remain to be elucidated. When used as a tocolytic (pharmacological agent that stops uterine contractions), it is administered transdermally (24-48 h). Here, we quantified the maternal and fetal steady-state plasma concentrations of maternal intravenous GTN in preterm sheep and continuously monitored maternal and fetal vascular parameters to observe possible dose-dependent vascular effects. Preterm (120 days gestation) pregnant sheep (n = 6) were instrumented with maternal femoral arterial (MA) and venous (MV) and fetal femoral arterial (FA) and umbilical venous (UV) polyethylene blood-sampling catheters. During maternal GTN infusion (3.0 micro, 60-min duration) the steady-state GTN concentrations ([GTN]) were as follows: MA, 98.6 +/- 9.0 nM; UV, 17.4 +/- 7.6 nM; and FA, GTN] was established by 5 min, and the UV/MA ratio of [GTN] was 0.18. The FA [GTN] (GTN in the UV, and the maternal and fetal heart rate and mean arterial pressure appear to be independent of maternal GTN infusion.

  7. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    Hougaard Pedersen, Sara; Maretty, Lasse; Ramachandran, Roshni; Sibbesen, Jonas Andreas; Yakimov, Victor; Elgaard-Christensen, Rikke; Hansen, Thomas Folkmann; Krogh, Anders; Olesen, Jes; Jansen-Olesen, Inger


    Introduction Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate transcriptional responses to GTN-infusion in the rat trigeminal ganglia. Methods Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed a novel method for Gene Set Analysis Of Variance (GSANOVA) to identify gene sets associated with transcriptional changes across time. Results 15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down-regulation in the 90-minute period after infusion. The GSANOVA analysis demonstrate enrichment of pathways pointing towards an increase in immune response, signal transduction, and neuroplasticity in response to GTN-infusion. Future functional in-depth studies of these mechanisms are expected to increase our understanding of migraine pathogenesis. PMID:27213950

  8. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    Jedrzkiewicz, Sean; Parker, John D


    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans.

  9. Systemic glyceryl trinitrate reduces anal sphincter tone: is there a therapeutic indication?

    Connolly, C; Tierney, S; Grace, P


    Nitric oxide (NO) has diverse roles as a biological messenger. [1] Topically applied nitrate donors cause relaxation of the internal anal sphincter (IAS) and facilitate healing of anal fissures [2,3]. Systemic nitrates are commonly used for the treatment of ischaemic heart disease, yet the effects of systemically administered nitrates on the smooth muscle of the IAS are unknown. Our aim was to test the hypothesis that systemically administered nitrates at a normal dose, cause inhibition of anal sphincter activity. With fully informed consent, anal manometry was performed on nine volunteers. Maximum and mean anal resting pressure (representing the IAS), maximum squeeze pressure (representing the external anal sphincter), heart rate and blood pressure were measured, before and after administration of a normal 400 μg dose of sublingual glyceryl trinitrate spray. Data are expressed as mean (± standard error of the mean (SEM)). In four females and five males ranging from 19 to 50 years of age, administration of GTN resulted in a significant reduction in systolic blood pressure from 138 ± 5 to 127 ± 4 mmHg, P anal sphincter function.

  10. Formation of "solvent-free" black lipid bilayer membranes from glyceryl monooleate dispersed in squalene.

    White, S H


    A simple technique for forming "black" lipid bilayer membranes containing negligible amounts of alkyl solvent is described. The membranes are formed by the method of Mueller et al (Circulation. 1962. 26:1167.) from glyceryl monooleate (GMO) dispersed in squalene. The squalene forms an annulus to satisfy the boundary conditions of the planar bilayer but does not appear to dissolve noticeably in the bilayer itself. The specific geometric capacitance (Cg) of the membranes at 20 degrees C formed by this technique is 0.7771 +/- 0.0048 muF/cm2. Theoretical estimates of Cg for solvent-free bilayers range from 0.75 to 0.81 muF/cm2. Alkane-free GMO bilayers formed from n-octadecane by the solvent freeze-out method of White (Biochim. Biophys. Acta. 1974. 356:8) have values of Cg = 0.7903 +/- 0.0013 muF/cm2 at 20.5 degrees C. The agreement between the various values of Cg strongly suggests that the bilayers are free of squalene. DC potentials applied to the bilayers have no detectable effect on the value of Cg, as expected for solvent-free films. The ability to form bilayers essentially free of the solvent used in the forming solution makes it possible to determine the area per molecule of the surface active lipid in the bilayer. The area per molecule of GMO at 20 degrees C is estimated to be 37.9 +/- 0.2 A2.

  11. Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats

    Christensen, Sarah Louise T; Petersen, Steffen; Sørensen, Dorte Bratbo


    Introduction: Glyceryl trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy....... In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. Methods: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl...... trinitrate on these behaviors in female rats was observed. Results: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None...

  12. Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact chest rat.

    Nossaman, Bobby D; Pankey, Edward A; Badejo, Adeleke R; Casey, David B; Uppu, Satvika; Murthy, Subramanyam N; Kadowitz, Philip J


    Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species.

  13. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

    Badejo, Adeleke M; Hodnette, Chris; Dhaliwal, Jasdeep S; Casey, David B; Pankey, Edward; Murthy, Subramanyam N; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J


    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

  14. Continuous twin screw melt granulation of glyceryl behenate: Development of controlled release tramadol hydrochloride tablets for improved safety.

    Keen, Justin M; Foley, Connor J; Hughey, Justin R; Bennett, Ryan C; Jannin, Vincent; Rosiaux, Yvonne; Marchaud, Delphine; McGinity, James W


    Interest in granulation processes using twin screw extrusion machines is rapidly growing. The primary objectives of this study were to develop a continuous granulation process for direct production of granules using this technique with glyceryl behenate as a binder, evaluate the properties of the resulting granules and develop controlled release tablets containing tramadol HCl. In addition, the granulation mechanism was probed and the polymorphic form of the lipid and drug release rate were evaluated on stability. Granules were prepared using a Leistritz NANO16 twin screw extruder operated without a constricting die. The solid state of the granules were characterized by differential scanning calorimetry and X-ray diffraction. Formulated tablets were studied in 0.1N HCl containing 0-40% ethanol to investigate propensity for alcohol induced dose dumping. The extrusion barrel temperature profile and feed rate were determined to be the primary factors influencing the particle size distribution. Granules were formed by a combination immersion/distribution mechanism, did not require subsequent milling, and were observed to contain desirable polymorphic forms of glyceryl behenate. Drug release from tablets was complete and controlled over 16 h and the tablets were determined to be resistant to alcohol induced dose dumping. The drug release rate from the tablets was found to be stable at 40°C and 75% relative humidity for the duration of a 3 month study.

  15. Rheology of oleo gels based on sorbitan and glyceryl mono stearates and vegetable oils for lubricating applications

    Sanchez, R.; Franco, J. M.; Delgado, M. A.; Valencia, C.; Gallegos, C.


    Oleo gels based on sorbitan and glyceryl mono stearates and different types of vegetable oils, potentially applicable as biodegradable alternatives to traditional lubricating greases, have been studied. In particular, the rheological behavior, by means of small-amplitude oscillatory shear (SAOS) measurements, and some lubrication performance-related properties (mechanical stability and tribological response) have been evaluated in this work. SAOS response and mechanical stability of these oleo gels are significantly influenced by the type and concentration of the organogelator and the vegetable oil used in the formulations. Glyceryl monostearate (GMS) generally produces stronger gels than sorbitan monostearate (SMS). The use of low-viscosity oils, such as rapeseed and soybean oils, yields gels with significantly higher values of the linear viscoelastic functions than oleo gels prepared with high-viscosity oils, i.e. castor oil. The rheological behavior of SMS-based oleo gels also depends on the cooling rate applied during the gelification process. On the other hand, the oleo gels studied present low values of the friction coefficient obtained in a tribological contact, although only some GMS/castor oil-based oleo gels exhibit a suitable mechanical stability. (Author) 28 refs.

  16. Side effects of glyceryl trinitrate ointment for primary dysmenorrhea: a randomized clinical trial

    Rahnama P.


    Full Text Available Background: Patch forms of glyceryl trinitrate (GTN, also known as nitroglyceril, have proved useful in the management of dysmenorrhea. Increased intrauterine pressure due to exaggerated myometrial contractions is an important factor in the pathogenesis of dysmenorrhea. In a recent study, it was found that GTN caused a significant reduction in the contraction frequency of human myometrial strips. The object of this study is to evaluate the efficacy of GTN ointment in treating primary dysmenorrhea.Methods: In this double-blind randomized placebo-controlled study, we enrolled 112 unmarried subjects with the complaint of moderate to severe primary dysmenorrhea. They were between 18-30 years of age with normal BMI (19-27 and all had normal results upon examination by pelvic ultrasound. None of these patients had a history anemia, previous pelvic surgery or cardiovascular diseases. Randomly divided in two groups using odd and even numbers, 56 of the subjects received 5 mg 1% GTN ointment and another 56 received a placebo. Before starting the treatment, severity of pain was recorded using a visual scale method. Ointment A (GTN 1% or ointment B (placebo was applied to special papers which were in turn applied to the skin of the abdomen below the umbilicus, and left there for the entire treatment period of four hours. The severity of pain and side effects of the treatment were recorded at intervals of 15 min, 30 min, 1 h, 2 h and 4 h after application the treatment. After four hours, the treatment was removed and the skin checked for erythema. Results: There was no difference in severity of pain 15 min after treatment, but pain was less severe in the GTN group from the 30-min interval through the 4-h interval, with the least pain felt at the 2-h interval. This decrease in pain lasted through the 4-h interval. Side effects, which were more common in the GTN group than the placebo group (P<0.05, included headache (48.3% vs. 19.5%, respectively, dizziness

  17. Synthesis of Monoalkyl Glyceryl Ethers by Ring Opening of Glycidol with Alcohols in the Presence of Lewis Acids.

    Cucciniello, Raffaele; Ricciardi, Maria; Vitiello, Rosa; Di Serio, Martino; Proto, Antonio; Capacchione, Carmine


    The present work deals with the production of monoalkyl glyceryl ethers (MAGEs) through a new reaction pathway based on the reaction of glycidol and alcohols catalyzed by Lewis acid-based catalysts. Glycidol is quantitatively converted with high selectivity (99 %) into MAGEs under very mild reaction conditions (80 °C and 0.01 mol % catalyst loading) in only 1 h using Al(OTf)3 or Bi(OTf)3 as catalyst. The proposed method enhances the choice of possible green synthetic approaches for the production of value-added products such as MAGEs. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles

    Jie Lai


    Full Text Available Jie Lai1,2, Yi Lu1, Zongning Yin2, Fuqiang Hu3, Wei Wu11School of Pharmacy, Fudan University, Shanghai, China, 2West China School of Pharmacy, Sichuan University, Chengdu, China, 3School of Pharmacy, Zhejiang University, Hangzhou, ChinaAbstract: Efforts to improve the oral bioavailability of cyclosporine A (CyA remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral®; higher Cmax (1371.18 ± 37.34 vs 969.68 ± 176.3 ng mL-1, higher AUC0–t (7757.21 ± 1093.64 vs 4739.52 ± 806.30 ng h mL-1 and AUC0–∞ (9004.77 ± 1090.38 vs 5462.31 ± 930.76 ng h mL-1. The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC0–∞ was about 178% as compared to Neoral®. The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.Keywords: nanoparticles, cubosomes, cyclosporine A, glyceryl monooleate, oral drug delivery, bioavailability, beagle dogs


    Madhu Lata


    Full Text Available OBJECTIVE: To compare the efficacy, associated side effects in short term as well as long term use of topical Diltiazem and topical GTN in the management of chronic anal fissure. MATERIAL AND METHODS: Out patients records of 231 patients with chronic anal fissure who reported to hospital from August 2011 to August 2014 and treated were randomly selected for both types of management of which 118 patients had received topical 2% diltiazem and 113 were treated with 0.2% glyceryl trinitrate topical ointment thrice daily for 6 weeks. They were assessed at the time of presentation, then at the end of 1st week, 3rd week and at the end of 6th week of treatment. Records of patients with anal fissure due to other diseases like inflammatory bowel disease, malignancy, sexually transmitted diseases, previous treatment with local ointment or surgery, patients who required anal surgery for any concurrent disease like hemorrhoids, pregnant women, patients with significant cardiovascular conditions and patients who did not turned up for follow up were excluded. Signs and symptoms and side-effects were noted at the given time. RESULTS: The study results are comparable to national figures and other studies. CONCLUSION: Topical application of both the ointments, 2% Diltiazem and 0.2% Glyceryl trinitrate observed to be quite effective in treatment of chronic fissure in Ano. However, topical Diltiazem is preferred to topical glyceryl trinitrate due to its lesser side effects and long term better control

  20. Synthesis and intravenous infusion into the rat of glyceryl bisacetoacetate, 1-acetoacetamido-2, 3-propane diol, and partially reduced glucosyl pentaacetoacetate.

    Birkhahn, R H; Clemens, R J; Hubbs, J C


    The efficacy of parenteral nutrition could be improved by finding a more effective energy source. Esters of short-chain fatty acids have exhibited some promise as alternatives to glucose. The present study reports on two new esters and one amide, each containing acetoacetate as the organic acid. The three compounds: glyceryl bisacetoacetate, N-2',3'-dihydroxypropyl-3-oxo-butanamide (1-acetoacetamido-2,3-propane diol), and partially reduced glucosyl pentaacetoacetate, were synthesized and then continuously infused into rats for 7 d. The infusion rate provided 50% of the rats' estimated metabolic energy requirements, and rats were fed with a reduced-energy oral diet that provided the remaining 50% of energy plus adequate protein. Rat groups for each compound were: (1) experimental-compound-infused and ad libitum-fed, (2) isoenergetic glucose-infused and pairfed, and (3) saline infused and pair-fed. Body-weight changes, N losses and N retention were measured daily. All rats died from partially reduced glucosyl pentaacetoacetate infusion at 100% and 50% of the intended rate. Rats infused with 1-acetoacetamido-2,3-propane diol failed to gain weight and to increase the plasma ketone-body concentration. Glyceryl bisacetoacetate produced hyperketonaemia, and weight gain and N variables that were similar to those for glucose-infused rats. It was concluded that only glyceryl bisacetoacetate would make a satisfactory parenteral nutrient.

  1. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.

    Kruuse, C; Iversen, H K; Jansen-Olesen, I; Edvinsson, L; Olesen, J


    The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.

  2. 三羟甲基丙烷高纯油酸酯的制备及其作为液压油基础油的抗氧化研究%Preparation of Trihydroxymethylpropyl Trioleate with High Purity Oleic Acid and Study on Its Antioxidant Propriety as a Lubricant Base Oil

    孔令杰; 张东恒; 李鹏; 魏观为; 张雪涛; 连玉双


    High purity oleic acid was prepared via Diels-Alder reaction with technical grade 80 oleic acid using maleic anhydride, methyl acrylate and acrylic acid as dienophile respectively. The contents of oleic acid was increased up to nearly 90%. With the high purity oleic ac-id and technical grade 80 oleic acid respectively, two different trihydroxymethylpropyl trioleates(TMPTOs) were prepared by esterification, and were purified by molecular distillation. PDSC and rotary oxygen bomb were employed to evaluate the oxidation stabilities of two diffi-dent TMPTOs as lubricant base oils with the same additives package. The results showed that the antioxidant performance of TMPTO syn-thesisd with high purity oleic acid is,significantly improved compared to TMPTO synthesisd with 80 oleic acid. PDSC oxidation induction period raise nearly 1 times, and rotary oxygenbomb oxidation time increase from 121min to 198min.%采用马来酸酐、丙烯酸甲酯以及丙烯酸为亲双烯体分别与工业级的80油酸中的多不饱和酸进行Diels-Alder反应,并通过分子蒸馏分离出纯度近90%的油酸。采用制备的高纯油酸与三羟甲基丙烷进行酯化反应,并通过分子蒸馏分离提纯,得到了三羟甲基丙烷高纯油酸酯。使用PDSC和旋转氧弹等方法对合成的三羟甲基丙烷高纯油酸酯在液压油配方中进行了氧化安定性的分析测试,发现其抗氧化性相比于直接使用80油酸合成的同类酯显著提升,PDSC氧化诱导期提升近1倍,旋转氧弹氧化时间由121min提升至198min。

  3. Study on preparation of niosomes with glyceryl dilaurate%二月桂酸甘油酯类脂囊泡的制备及研究

    常兰; 颜丽


    用自制的二月桂酸甘油酯为原料,制备了包裹亲水性药物抗坏血酸的类脂囊泡。通过正交设计优化类脂囊泡制备工艺,最优条件为:超声时间为15min,水相温度为0℃,m(脂质):m(药物)=10:1,m(脂质):m(胆固醇)=2:1,得到了药物包封率最高约为34.6%。结果表明,以自制的非离子表面活性剂为原料能够形成包封率和稳定性较好的纳米药物载体,为纳米类脂囊泡的合成提供一种价格低廉且可工业化生产的原料。%VC was encapsulated in niosomes formed by glyceryl dilaurate via a ultrasound method.The preparation process was optimized by orthogonal experiment.The optimal conditions were found to be the ultrasound time 15min,the water temperature 0℃,the material and cholesterol ratio 2:1,the material and drug ratio 10:1.The highest entrapmention efficiency was 34.6%.The results showed that with self-made nonionic surfactant as raw material,nano drug carrier with good entrapmention efficiency and stability was obtained.Glyceryl dilaurate was a cheaply raw material and can be used in industrial production.

  4. Investigations into the chemistry and insecticidal activity of euonymus europaeus seed oil and methanol extract

    Euonymus europaeus seeds and seed oil were investigated for their volatiles using GC-MS-FID, Headspace-SPME/GC-MS-FID, and derivative GC-MS-FID for their volatiles and HPLC-DAD-CAD/MS for their non-volatile compounds. The seeds contain about 30% of fatty oil, mainly glyceryl trioleate, small amounts...

  5. Study on the Melting Point Determination of Glyceryl Monostearate%单硬脂酸甘油酯熔点分析方法研究

    杨燕; 欧阳晓岳; 叶南飚


    通过不同的熔点测试方法:两端开口毛细管法和数字熔点仪测定了单硬脂酸甘油酯(单甘酯)的熔点。结果表明,两端开口毛细管法测得的数据精密度较高,而且此法操作方便、重复性强、结果准确、经济。同时还总结了两端开口毛细管法测定熔点的影响因素及注意事项。%The mehing point of glyceryl monostearate (monoglyeeride) can indirectly reflect its purity, In order to accurately measure the melting point, this article through different testing methods, capillary method and digital melting point tester, measured the melting point of monoglycerides . The results show that the date gained by the latter are precise and exact.And this method is convenient, repeatability, and economy. This pa- per also analysis the factors which effect on determination of melting point of monoglycerides.

  6. The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC-GTN Study.

    Hamarneh, Ashraf; Sivaraman, Vivek; Bulluck, Heerajnarain; Shanahan, Hilary; Kyle, Bonnie; Ramlall, Manish; Chung, Robin; Jarvis, Claire; Xenou, Maria; Ariti, Cono; Cordery, Roger; Yellon, Derek M; Hausenloy, Derek J


    Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial ( NCT01864252). The ERIC-GTN trial is a single-site, double-blind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting ± valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.

  7. Opposite reactivity of meningeal versus cortical microvessels to the nitric oxide donor glyceryl trinitrate evaluated in vivo with two-photon imaging.

    Evgeny Pryazhnikov

    Full Text Available Vascular changes underlying headache in migraine patients induced by Glyceryl trinitrate (GTN were previously studied with various imaging techniques. Despite the long history of medical and experimental use of GTN, its effects on the brain vasculature are still poorly understood presumably due to low spatial resolution of the imaging modalities used so far. We took advantage of the micrometer-scale vertical resolution of two-photon microscopy to differentiate between the vasodynamic effects of GTN on meningeal versus cortical vessels imaged simultaneously in anesthetized rats through either thinned skull or glass-sealed cranial window. Intermediate and small calibre vessels were visualized in vivo by imaging intravascular fluorescent dextran, and detection of blood flow direction allowed identification of individual arterioles and venules. We found that i.p.-injected GTN induced a transient constriction of meningeal arterioles, while their cortical counterparts were, in contrast, dilated. These opposing effects of GTN were restricted to arterioles, whereas the effects on venules were insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the diameter of meningeal vessels but induced a constriction of cortical vessels. The different cellular environment in cortex versus meninges as well as distinct vessel wall anatomical features probably play crucial role in the observed phenomena. These findings highlight differential region- and vessel-type-specific effects of GTN on cranial vessels, and may implicate new vascular mechanisms of NO-mediated primary headaches.

  8. Glyceryl trinitrate metabolism in the quail embryo by the glutathione S-transferases leads to a perturbation in redox status and embryotoxicity.

    Bardai, Ghalib K; Hales, Barbara F; Sunahara, Geoffrey I


    Exposure of stage 9 quail (Coturnix coturnix japonica) embryos to glyceryl trinitrate (GTN) induces malformations that were associated in previous studies with an increase in protein nitration. Increased nitration suggests metabolism of GTN by the embryo. The goals of this study were to characterize the enzymes and co-factors required for GTN metabolism by quail embryos, and to determine the effects of in ovo treatment with N-acetyl cysteine (NAC), a precursor of glutathione (GSH), on GTN embryotoxicity. GTN treatment of quail embryos resulted in an increase in nitrite, a decrease in total GSH, and an increase in the ratio of NADP(+)/NADPH, indicating that redox balance may be compromised in exposed embryos. Glutathione S-transferases (GSTs; EC purified from the whole embryo (K(m) 0.84 mM; V(max) 36 μM/min) and the embryonic eye (K(m) 0.20 mM; V(max) 30 μM/min) had GTN-metabolizing activity (1436 and 34 nmol/min/mg, respectively); the addition of ethacrynic acid, an inhibitor of GST activity, decreased GTN metabolism. Peptide sequencing of the GST isozymes indicated that alpha- or mu-type GSTs in the embryo and embryonic eye had GTN metabolizing activity. NAC co-treatment partially protected against the effects of GTN exposure. Thus, GTN denitration by quail embryo GSTs may represent a key initial step in the developmental toxicity of GTN.

  9. Stabilizing effect of cetostearyl alcohol and glyceryl monostearate as co-emulsifiers on hydrocarbon-free O/W glyceride creams.

    Ballmann, C; Mueller, B W


    The structure of a stable O/W cream is characterized by a more or less pronounced mixed crystal bilayer. The addition of co-emulsifiers in order to achieve a soft formulation often leads to a mixed crystal bilayer network of high viscosity and even phase separation. In order to ovoid this components of different chemical identities are used which often are not inert or harmless if they are absorbed. For this reason it seems to be interesting to use only components from one chemical family, e.g. to use only glycerides and their derivatives because in the case of absorption they are metabolized. The disadvantages of glyceride creams are, however, their low viscosity. The aim of this investigation was to find the optimum amount of co-emulsifier as consistency excipient for the basic formulation of an O/W glyceride cream. This was achieved by using differential scanning calorimetry; thermogravimetry, oscillation rheology and various stress tests. The amount of co-emulsifier used should not be too high, as it would crystallize increasingly during storage which gives the preparation an optical inhomogenity and a lack in softness which is needed for a suitable cosmetic acceptance. A slightly higher concentration than is necessary for the mixed emulsifier system can be advantageous, as the formation of a separate crystalline lipophilic network in the preparation increases its viscosity which will lead to a higher physico-chemical stability of the formulation. These results were obtained with the co-emulsifiers glyceryl monostearate (Imwitor 900), cetylstearyl alcohol (Lanette O), and PEG-20-glycerolstearate (Tagat S2) as O/W emulsifier. As oil phase a mixture of Miglyol 812 (caprylic/capric triglyceride) and Avocado oil was used.

  10. Protective effects of riboflavin and selenium on brain microsomal Ca2+-ATPase and oxidative damage caused by glyceryl trinitrate in a rat headache model.

    Nazıroğlu, Mustafa; Çelik, Ömer; Uğuz, Abdulhadi Cihangir; Bütün, Ayşe


    Migraine headaches are considered to be associated with increased mitochondrial energy metabolism. Mitochondrial oxidative stress is also important in migraine headache pathophysiology although riboflavin and selenium (Se) induced a modulator role on mitochondrial oxidative stress in the brain. The current study aimed to determine the effects of Se with/without riboflavin on the microsomal membrane Ca(2+)-ATPase (MMCA), lipid peroxidation, antioxidant, and electroencephalography (EEG) values in glyceryl trinitrate (GTN)-induced brain injury rats. Thirty-two rats were randomly divided into four groups. The first group was used as the control, and the second group was the GTN group. Se and Se plus oral riboflavin were administered to rats constituting the third and fourth groups for 10 days prior to GTN administration. The second, third, and fourth groups received GTN to induce headache. Ten hours after the administration of GTN, the EEG records and brain cortex samples were obtained for all groups. Brain cortex microsomes were obtained from the brain samples. The brain and microsomal lipid peroxidation levels were higher in the GTN group compared to the control group, whereas they were decreased by selenium and selenium + riboflavin treatments. Vitamin A, vitamin C, vitamin E, and reduced glutathione (GSH) concentrations of the brain and MMCA, GSH and glutathione peroxidase values of microsomes were decreased by the GTN administration, although the values and β-carotene concentrations were increased by Se and Se + riboflavin treatments. There was no significant change in EEG records of the four groups. In conclusion, Se with/without riboflavin administration protected against GTN-induced brain oxidative toxicity by inhibiting free radicals and the modulation of MMCA activity and supporting the antioxidant redox system.

  11. Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: a double-blind, placebo-controlled, cross-over study.

    Perrotta, Armando; Serrao, Mariano; Tassorelli, Cristina; Arce-Leal, Natalia; Guaschino, Elena; Sances, Grazia; Rossi, Paolo; Bartolo, Michelangelo; Pierelli, Francesco; Sandrini, Giorgio; Nappi, Giuseppe


    Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2 ± 8.2) migraine and 15 (11 F; 4M; mean age 35.9 ± 8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30', 60', 120', 180' and 240' after GTN (0.9 mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60', 120' and 180' after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60', 120' and 180' after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN.

  12. Selective anti-platelet aggregation synergism between a prostacyclin-mimetic, RS93427 and the nitrodilators sodium nitroprusside and glyceryl trinitrate.

    Willis, A L; Smith, D L; Loveday, M; Fulks, J; Lee, C H; Hedley, L; VanAntwerp, D


    1. Citrated platelet-rich plasma from human donors was used to examine turbidometrically the platelet aggregation response to collagen (2.5 micrograms ml-1) and ADP (1.6 microgram ml-1). 2. With collagen as an aggregating agent, the limited (35% maximal inhibition) inhibitory effects of glyceryl trinitrate (GTN, 0.78-50 micrograms ml-1) were markedly potentiated by threshold (3.3-10 ng ml-1) concentrations of RS93427, an orally active prostacyclin-mimetic. Almost complete inhibition of aggregation could then be produced. 3. A threshold concentration of RS93427 (3.3 ng ml-1) similarly potentiated the ability of sodium nitroprusside (NaNp, 0.78-10 micrograms ml-1) to inhibit collagen-induced platelet aggregation. There was an 8 fold reduction in the IC25 concentration of NaNp. 4. Threshold concentrations of the nitrodilators were also able to potentiate the anti-aggregatory effects of RS93427 (0.03-30 ng ml-1) on collagen-induced platelet aggregation. With threshold concentrations of either GTN (6.3-25 micrograms ml-1) or NaNp (0.3-1.3 microgram ml-1), the mean IC50 concentration of RS93427 was reduced 4 or 6 fold, respectively, while the IC25 concentration was reduced 6 or 10 fold, respectively. 5. No similar synergistic interactions were seen between RS93427 and the nitrodilators when ADP was used as an aggregating agent. 6. In spontaneously hypertensive rats, the dose-response for the hypotensive response to bolus doses of RS93427 was not altered by concomitant steady state infusion of a threshold dose (1 micrograms kg-1 min-1) of GTN. 7. Possible therapeutic implications of these findings are discussed.

  13. Direct demonstration of nitric oxide formation in organs of rabbits treated by transdermal glyceryl trinitrate using an in vivo spin trapping technique.

    Clermont, Gaëlle; Lecour, Sandrine; Vergely, Catherine; Zeller, Marianne; Perrin, Caroline; Maupoil, Véronique; Bouchot, Olivier; Rochette, Luc


    Glyceryl trinitrate (GTN) is commonly delivered by a patch for the treatment of angina pectoris. The idea is now generally accepted that GTN requires a biotransformation process that activates the drug, in particular through nitric oxide (NO) generation. However, the pharmacokinetics of NO delivery from GTN still remains obscure. The objective of this study was to assess GTN-derived NO formation in vascular tissues and organs in rabbit given GTN patches. NO levels were evaluated in rabbits after 3 h of treatment with a 10 mg GTN patch (GTN group; n = 7) or a placebo patch (CTL; n = 7). Nitrosylhaemoglobin (HbNO) was evaluated by electron spin resonance (ESR) spectroscopy in red cell suspension. In vivo spin trapping technique using FeMGD as a spin trap, associated with ESR was used to quantify NO in tissues. The NO-spin trap complex, which is a relatively stable product, has been measured in several tissues. The ESR spectrum corresponding to HbNO was not found in red cell of GTN or CTL rabbits. The spectrum corresponding to the NO-spin trap complex was observed in all analysed tissues of CTL rabbits. The signal was significantly increased in liver, renal medulla, heart left ventricle and spleen of GTN-treated rabbits, and to a lesser extent in right ventricle and lung. No difference was shown between NO-spin trap levels measured in aorta or inferior vena cava from GTN or CTL rabbits. These data suggest that GTN patch treatment induced NO release, and that tissue-specific differences in transdermal GTN-derived NO exist. The GTN-NO pathway appears to be largely involved in organs such as the liver, kidney and heart.

  14. Riboflavin and vitamin E increase brain calcium and antioxidants, and microsomal calcium-ATP-ase values in rat headache models induced by glyceryl trinitrate.

    Bütün, Ayşe; Nazıroğlu, Mustafa; Demirci, Serpil; Çelik, Ömer; Uğuz, Abdulhadi Cihangir


    The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, β-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin.

  15. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials.

    Jiexia Ding

    Full Text Available BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP. Several clinical trials used glyceryl trinitrate (GTN to prevent the incidence of post-ERCP pancreatitis (PEP. However, the results were still controversial. OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia. METHODS: Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials. RESULTS: Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87. Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15. Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90. No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06 attributable to GTN were observed. CONCLUSION: Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.

  16. Topical glyceryl trinitrate in the treatment of anal fissure Utilidad del gliceril trinitrato en el tratamiento tópico de la fisura anal

    F. Novell


    Full Text Available Aim: the aim of this study was to assess the effectiveness of topical glyceryl trinitrate (GTN in the treatment of anal fissure. Patients: eighty consecutive patients were randomized to receive 0.2% GTN gel twice a day during a minimum of 6 weeks. Of these 80 patients 34 were males and 46 female, with ages be-tween 20 and 78 years. All patients underwent a work-up that included gender, age, symptom duration, site, previous treatment attempts, pain score, associated diseases, and maximum anal resting pressure. These patients were followed at regular intervals of 4, 8, and 12 weeks to assess symptom outcome, rate of healing, adverse effects, and recurrence rate. Results: pain scores were significantly reduced during the treatment period in 65% of cases. After 4 weeks, 55% of patients had healed, and 78% after 9 weeks. In 18 patients (22%, anal fissures did not heal even with 6 additional weeks of treatment, and 12 of them (15% underwent lateral sphincterotomy. Sixty one percent of patients had flushing and 15% severe headaches. Conclusion: the results of this study have demonstrated the significant benefit of topical GTN when administered to patients suffering from anal fissures.Objetivo: el objetivo de este estudio era la valoración de la aplicación tópica de gliceril trinitrato en el tratamiento de las fisuras anales. Pacientes: un total de 80 consecutivos pacientes eran randomizados recibiendo gliceril trinitrato al 0,2% gel dos veces al día, durante un mínimo de 6 semanas. De los 80 pacientes, 34 eran varones y 46 mujeres, con edad comprendida entre 20 y 78 años. En los pacientes se controlaba sexo, edad, duración de síntomas, duración de tratamiento, localización, patología previa asociada, y valoración del dolor. Seguimiento a 4, 8 y 12 semanas, para controlar la sintomatología, el grado de curación, los efectos adversos y la relación de recidiva. Resultados: la disminución del dolor fue significativa en el 65% de los casos y

  17. Curative effect analysis of therapeutic ultrasonic in vitro on hyperlipemia%体外治疗性超声降脂效果分析

    董亚红; 雷革胜; 张宝华; 林宏; 宣力


    Objective To observe the effects of therapeutic ultrasound in vitro on hyperlipemia. Methods Comparing clinical effects of only ultrasound treatment, only administration of Geminifbrozip and combination of these two therapies. These patientswere divided into three groups and the follow up observation was 3 months. Result Curative effect of the ultrasound group was better than that of drug group (P< 0.05). Curative effect of the combined therapy group was the best(P< 0.01). Result of follow up suggested that serum glyceryl trioleate and cholesterol relapse rate of ultrasonic group was lower than that of drug group .Serum glyceryl trioleate and cholesterol relapse rate of combined therapy group was the lowest. Conclusion Combination of ultrasound treatment in vitro and administration of Geminifbrozip is the best way to treat hyperlipemia, and it is not easy to relapse.

  18. Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials

    Philip M. Bath


    Full Text Available Background. Nitric oxide (NO donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants were identified, all involving glyceryl trinitrate (GTN. Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR 0.52, 95% confidence interval (CI 0.34–0.78 and reduced death (OR 0.32, 95% CI 0.14–0.78. Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

  19. 硝酸甘油消化道吸收后在动物体内的代谢研究%Studies of Metabolic Glyceryl Trinitrate Absorbed through Alimentary Canal

    张阳东; 田亚平; 汪德清; 宋淑珍; 董矜; 姜辉


    目的观察硝酸甘油(glyceryl trinitrate, GTN)经消化道吸收后的分解代谢机理.方法以实验兔为动物模型,应用电生理监测仪动态检测血压,血气分析仪检测高铁血红蛋白(MetHb),全自动生化分析仪检测丙氨酸氨基转移酶(ALT),比色法检测硝酸盐、亚硝酸盐、还原型谷胱甘肽(GSH).结果 GTN经消化道吸收后代谢产生亚硝酸盐,实验动物血压、红细胞GSH降低,MetHb、ALT未见明显变化.结论机体内GTN分解代谢过程中可消耗还原性巯基和产生亚硝酸盐,对血红蛋白和肝脏功能无明显影响.

  20. Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials

    Bath, Philip M.; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A.; Robinson, Thompson G.; Saver, Jeffrey L.; Sprigg, Nikola; Wardlaw, Joanna M.; in Acute Stroke Collaboration (BASC), Blood pressure


    Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke. PMID:27190674

  1. Final report on the safety assessment of Ricinus Communis (Castor) Seed Oil, Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE, Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate, Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate, Methyl Ricinoleate, and Octyldodecyl Ricinoleate.


    The oil derived from the seed of the Ricinus communis plant and its primary constituent, Ricinoleic Acid, along with certain of its salts and esters function primarily as skin-conditioning agents, emulsion stabilizers, and surfactants in cosmetics, although other functions are described. Ricinus Communis (Castor) Seed Oil is the naming convention for castor oil used in cosmetics. It is produced by cold pressing the seeds and subsequent clarification of the oil by heat. Castor oil does not contain ricin because ricin does not partition into the oil. Castor oil and Glyceryl Ricinoleate absorb ultraviolet (UV) light, with a maximum absorbance at 270 nm. Castor oil and Hydrogenated Castor Oil reportedly were used in 769 and 202 cosmetic products, respectively, in 2002; fewer uses were reported for the other ingredients in this group. The highest reported use concentration (81%) for castor oil is associated with lipstick. Castor oil is classified by Food and Drug Administration (FDA) as generally recognized as safe and effective for use as a stimulant laxative. The Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives established an acceptable daily castor oil intake (for man) of 0 to 0.7 mg/kg body weight. Castor oil is hydrolyzed in the small intestine by pancreatic enzymes, leading to the release of glycerol and Ricinoleic Acid, although 3,6-epoxyoctanedioic acid, 3,6-epoxydecanedioic acid, and 3,6-epoxydodecanedioic acid also appear to be metabolites. Castor oil and Ricinoleic Acid can enhance the transdermal penetration of other chemicals. Although chemically similar to prostaglandin E(1), Ricinoleic Acid did not have the same physiological properties. These ingredients are not acute toxicants, and a National Toxicology Program (NTP) subchronic oral toxicity study using castor oil at concentrations up to 10% in the diet of rats was not toxic. Other subchronic studies of castor oil produced similar findings

  2. 月桂酸二聚甘油酯硫酸酯钠盐的制备与表面性能%Preparation and surface properties of sodium lauric dimerized glyceryl sulfate

    史鸿鑫; 张辉; 武宏科; 陈立军; 项菊萍


    Lauric dimerized glycerol ester was synthesized from lauric acid and glycerol dimer,and then the intermediate ester was sulfated by chlorosulfonic acid and neutralized by NaOH solution to get the product sodium lauric dimerized glyceryl sulfate (SLDGS). The intermediate and product were characterized by FTIR. The surface chemical properties were investigated at 298 K. The surface tensions of SLDGS aqueous solution increase with the increasing esterification degree of glycerol dimmer with lauric acid. When its esterification degree is 25% ,the cmc is 1.15 mmol · L-1 and γcwc is 28. 5 mN · m-1. When esterification degree is 30% , emulsifying property of SLDGS aqueous solution with kerosene and benzene is the best,and the emulsification time is 168 s. Foaming performance of SLPGS is not good.%以二聚甘油和月桂酸为原料进行酯化反应得到月桂酸二聚甘油酯,再与氯磺酸反应,经氢氧化钠中和制得月桂酸二聚甘油酯硫酸酯钠盐(SLDGS).对中问体和产物进行了红外光谱分析,测定了产物在298 K下的表面化学性能.发现SLDGS水溶液的表面张力随着月桂酸酯化度的升高而增大,酯化度为25%时,最低表面张力为28.5 mN·m-1,临界胶束浓度为1.15 mmol·L-1;在煤油和苯中,当酯化度为30%时,SLDGS水溶液的乳化性能达到最大值,乳化时间为168 s;SLDGS水溶液的泡沫性能不佳.

  3. 21 CFR 184.1329 - Glyceryl palmitostearate.


    ... palmitostearate is a mixture of mono-, di-, and triglyceryl esters of palmitic and stearic acids made from glycerin, palmitic acid, and stearic acid. (b) The ingredient meets the following specifications: (1) The substance is a mixture of mono-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy...

  4. Glyceryl 1,3-Dipalmitate Produced from Lactobacillus paracasei subspecies. paracasei NTU 101 Inhibits Oxygen-Glucose Deprivation and Reperfusion-Induced Oxidative Stress via Upregulation of Peroxisome Proliferator-Activated Receptor γ in Neuronal SH-SY5Y Cells.

    Cheng, Meng-Chun; Pan, Tzu-Ming


    Glyceryl 1,3-dipalmitate (GD) purified from Lactobacillus paracasei subsp. paracasei NTU 101-fermented products has been demonstrated to possess neuroprotective properties. We determined the effect of GD on oxygen-glucose deprivation and reperfusion (OGD/R)-induced SH-SY5Y neuroblastoma cell death. GD ameliorated OGD/R-induced apoptosis by elevating the protein expression of nuclear peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), thereby attenuating reactive oxygen species (ROS) generation. Pretreatment with GD reduced nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) expression from 1.54 ± 0.27 to 0.84 ± 0.46, thereby attenuating the induction of pro-inflammatory mediators, and increased the plasma membrane Ca(2+) ATPase (PMCA) levels from 0.81 ± 0.02 to 1.08 ± 0.06, thus reducing the levels of cytosolic Ca(2+); this also correlated with reduced cell death. We conclude that GD prevents SH-SY5Y cells from injury after OGD/R insult, possibly by modulating oxidative stress and inflammatory response.

  5. Deactivation of Cu/Zn catalyst for hydrogenation of fatty acid methyl ester to fatty alcohol:effects of glycerine and glyceryl triacetate%月桂酸甲酯加氢制月桂醇Cu/Zn催化剂的失活:甘油和三乙酸甘油酯的影响

    黄辉; 王劭泓; 范春玲; 王余杰; 赵旭东; 曹贵平


    Natural fatty alcohols have become the important base feedstock of fine chemical industry. The lifetime of the commercial Cu/Zn catalyst was shortened· due to its deaetivation. Deactivation of Cu/Zn catalyst caused by glycerine and glyceryl triaeetate in hydrogenation of methyl lanrate to lanryl alcohol was studied. The catalysts were characterized by XRD, BET, TG-DTA, and the product was analyzed by GC-MS. The results indicated that glycerine and glyeeryl triacetate, in the presence of Cu/Zn catalyst,could be decomposed to oleophobic 1,2-propanediol and insoluble cross-linked solids, respoetively, which caused surface area decrement and deactivation of the catalyst by adsorption and then active site occlusion.%脂肪醇是精细化工的重要原料,工业Cu/Zn催化剂易失活,使用寿命较短.在间歇釜高压反应器中考察了甘油和三乙酸甘油酯对Cu/Zn催化剂上月桂酸甲酯加氢制月桂醇催化活性的影响,采用XRD、BET、GC-MS和TG-DTA等分析和表征方法对失活催化剂和反应产物进行了分析.结果表明,甘油和三乙酸甘油酯在催化剂作用下分别得到强疏油性的1,2-丙二醇和难溶的交联物,并吸附在催化剂上,导致催化剂活性中心被覆盖,催化剂比表面积减小,引起催化剂失活.

  6. Glyceryl trinitrate is a novel inhibitor of quorum sensing in ...

    cein, water saturated butanol (900 µl) was added followed by vortexing and ..... and even if systemic absorption occurs, GTN has a very short half-life (1 to 3 .... ruginosa sodA and sodB mutants defective in manganese- and iron cofactored ...

  7. Hemodynamic changes study of common carotid artery in migraine rat model induced by glyceryl trinitrate%硝酸甘油型实验性偏头痛大鼠模型颈总动脉血流动力学初探

    章正祥; 曹克刚; 范吉平


    Objective To study hemodynamic changes of common carotid artery in migraine rat model induced by glyc-eryl trinitrate (GTN). Methods Migraine rat model was established with GTN (10mg/kg,sc). Hemodynamic changes of blank group,normal saline group and GTN group after stable blood pressure for 10 minutes were monitored continuously by CBI pulsed Doppler flowmeter and BIOPAC multiplying channel physiological signal recorder for 6 hours, blood flow velocity, heart rate, sys-tolic blood pressure, diastolic blood pressure and mean arterial pressure were extracted at 1,2,3,4,5,6 hours with NOTOCORD-Hem 3.5 soft system. Results Blood flow velocity descended (-8.35±3.41)cm/s and(-7.84±3.90)cm/s after 1h and 2h of GTN sc, At 1h, 2h, 4h blood flow velocity change rate had decreased compared with normal saline group and blank group (P<0.05). Systolic blood pressure change Rate, diastolic blood pressure change rate and mean arterial blood pressure change rate in GTN group were lower more than normal saline group and blank group in the three time points of 1h, 2h, 4h (P<0.05). Conclusion Blood flow velocity of common carotid artery has continued to decline induced by GTN for the further study of migraine rat model provides experimental evidence.%  目的观察硝酸甘油(GTN)偏头痛大鼠模型颈总动脉血流动力变化.方法采用皮下注射 GTN 法建立偏头痛大鼠模型,应用 CBI 脉冲多普勒血流计、BIOPAC 多导生理信号记录仪对空白组、生理盐水组、硝酸甘油组血压稳定10min 后连续6h 监测血流动力变化,运用 NOTOCORD-Hem 3.5系统提取1、2、3、4、5、6h 等时间点的血流速度、心率、收缩压、舒张压、平均动脉压.结果 GTN 皮下注射后1h 及2h 血流速度分别降低(-8.35±3.41)cm/s 和(-7.84±3.90)cm/s,而1、2、4h 硝酸甘油组血流速度变化率与生理盐水组和空白组相比均下降(P<0.05).GTN sc 后收缩压变化率、舒张压变化率、平均动脉压变化率在1、2

  8. Emulsification at the Liquid/Liquid Interface: Effects of Potential, Electrolytes and Surfactants.

    Chowdhury, Mehrin; Kataky, Ritu


    Emulsification of oils at liquid/liquid interfaces is of fundamental importance across a range of applications, including detergency. Adsorption and partitioning of the anionic surface active ions at the interface between two immiscible solutions is known to cause predictable chaos at the transfer potential region of the surfactant. In this work, the phenomenon that leads to the chaotic behaviour shown by sodium dodecylbenzene sulfonate (SDBS) at the water/1,2-dichloroethane interface is applied to commercial surfactants and aqueous/glyceryl trioleate interface. Electrochemical methods, electrocapillary curves, optical microscopy and conductivity measurements demonstrated that at 1.5 mm of SDBS, surfactants are adsorbed at the interface and assemble into micelles, leading to interfacial instability. As the concentration of the anionic surfactant was enhanced to 8 and 13.4 mm, the Marangoni effect and the interfacial emulsification became more prominent. The chaotic behaviour was found to be dependent on the surfactant concentration and the electrolytes present.

  9. Characterization of an Alkaline Family I.4 Lipase from Bacillus sp. W130-35 Isolated from a Tidal Mud Flat with Broad Substrate Specificity.

    Kim, Hee Jung; Jung, Won Kyeong; Lee, Hyun Woo; Yoo, Wanki; Kim, T Doohun; Kim, Hoon


    A gene encoding lipolytic enzyme, lip7-3, was isolated from Bacillus sp. W130-35 isolated from a tidal mud flat. The gene encoded a protein of 215 amino acids with a signal peptide composed of 34 amino acid residues. Lip7-3 belonged to the family I.4 lipase and showed its maximal activity at pH 9.0 and 60°C. Its activity increased in the presence of 30% methanol and, remarkably, increased as well to 154.6% in the presence of Ca(2+). Lip7-3 preferred pnitrophenyl octanoate (C8) as a substrate and exhibited broad specificity for short- to longchain fatty acid esters. Additionally, Lip7-3 showed a low degree of enantioselectivity for an S-enantiomer (e.g., (S)-methyl-3-hydroxy-2-methylpropionate). It efficiently hydrolyzed glyceryl tributyrate, but did not hydrolyze glyceryl trioleate, fish oil, or olive oil. Its substrate specificity and activation by the solvent might offer a merit to the biotechnological enzyme applications like transesterification in the production of biodiesel.

  10. Delayed migraine-like headache in healthy volunteers after a combination of acetazolamide and glyceryl trinitrate

    Daugaard, D.; Iversen, H. K.; Olesen, Jes;


    cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14...

  11. Citrem Modulates Internal Nanostructure of Glyceryl Monooleate Dispersions and Bypasses Complement Activation

    Wibroe, Peter P; Mat Azmi, Intan Diana Binti; Nilsson, Christa;


    Lyotropic non-lamellar liquid crystalline (LLC) aqueous nanodispersions hold a great promise in drug solubilization and delivery, but these nanosystems often induce severe hemolysis and complement activation, which limit their applications for safe intravenous administration. Here, we engineer an...

  12. In-vivo evaluation of clindamycin release from glyceryl monooleate-alginate microspheres by NIR spectroscopy.

    Mohamed, Amir Ibrahim; Ahmed, Osama A A; Amin, Suzan; Elkadi, Omar Anwar; Kassem, Mohamed A


    The purpose of this study was to use near-infrared (NIR) transmission spectroscopic technique to determine clindamycin plasma concentration after oral administration of clindamycin loaded GMO-alginate microspheres using rabbits as animal models. Lyophilized clindamycin-plasma standard samples at a concentration range of 0.001-10 μg/ml were prepared and analyzed by NIR and HPLC as a reference method. NIR calibration model was developed with partial least square (PLS) regression analysis. Then, a single dose in-vivo evaluation was carried out and clindamycin-plasma concentration was estimated by NIR. Over 24 h time period, the pharmacokinetic parameters of clindamycin were calculated for the clindamycin loaded GMO-alginate microspheres (F3) and alginate microspheres (F2), and compared with the plain drug (F1). PLS calibration model with 7-principal components (PC), and 8000-9200 cm(-1) spectral range shows a good correlation between HPLC and NIR values with root mean square error of cross validation (RMSECV), root mean square error of prediction (RMSEP), and calibration coefficient (R(2)) values of 0.245, 1.164, and 0.9753, respectively, which suggests that NIR transmission technique can be used for drug-plasma analysis without any extraction procedure. F3 microspheres exhibited controlled and prolonged absorption Tmax of 4.0 vs. 1.0 and 0.5 h; Cmax of 2.37±0.3 vs. 3.81±0.8 and 5.43±0.7 μg/ml for F2 and F1, respectively. These results suggest that the combination of GMO and alginate (1:4 w/w) could be successfully employed for once daily clindamycin microspheres formulation which confirmed by low Cmax and high Tmax values.

  13. Effect of a nitric oxide donor (glyceryl trinitrate) on nociceptive thresholds in man

    Thomsen, L L; Brennum, J; Iversen, Helle Klingenberg


    thresholds in man. On two different study days separated by at least a week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min, 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each...

  14. Characterization of a Novel Alkaline Family VIII Esterase with S-Enantiomer Preference from a Compost Metagenomic Library.

    Lee, Hyun Woo; Jung, Won Kyeong; Kim, Yong Ho; Ryu, Bum Han; Kim, T Doohun; Kim, Jungho; Kim, Hoon


    A novel esterase gene, est7K, was isolated from a compost metagenomic library. The gene encoded a protein of 411 amino acids and the molecular mass of the Est7K was estimated to be 44,969 Da with no signal peptide. Est7K showed the highest identity of 57% to EstA3, which is an esterase from a drinking water metagenome, when compared with the enzymes with reported properties. Est7K had three motifs, SMTK, YSV, and WGG, which correspond to the typical motifs of family VIII esterases, SxxK, Yxx, and WGG, respectively. Est7K did not have the GxSxG motif in most lipolytic enzymes. Three additional motifs, LxxxPGxxW, PLGMxDTxF, and GGxG, were found to be conserved in family VIII enzymes. The results of the phylogenetic analysis and the alignment study suggest that family VIII enzymes could be classified into two subfamilies, VIII.1 and VIII.2. The purified Est7K was optimally active at 40°C and pH 10.0. It was activated to exhibit a 2.1-fold higher activity by the presence of 30% methanol. It preferred short-length p-nitrophenyl esters, particularly p-nitrophenyl butyrate, and efficiently hydrolyzed glyceryl tributyrate. It did not hydrolyze β-lactamase substrates, tertiary alcohol esters, glyceryl trioleate, fish oil, and olive oil. Est7K preferred an Senantiomer, such as (S)-methyl-3-hydroxy-2-methylpropionate, as the substrate. The tolerance to methanol and the substrate specificity may provide potential advantage in the use of the enzyme in pharmaceutical and other biotechnological processes.

  15. Study on the clinical application of /sup 125/I-triolein/glycerol-/sup 75/Se-triether fat assimilation test for the detection of steatorrhea. Untersuchung zur klinischen Verwendbarkeit des /sup 125/J-Triolein/Glycerol-/sup 75/Se-Triether-Fettassimilationstests zur Erfassung einer Steatorrhoe

    Loesler, A.


    The principle of the fat assimilation test system (FATS) depends on the measurement of fecal radionuclide excretion after an oral administration of glyceryl-125I-trioleate (=125I-triolein) as a fat marker and glycerol-75Se-triether as a non-resorbable marker of the fat phase and on the relationship of the activities of both markers in a small stool sample to a titrimetrically determinable stool fat excretion. A complete stool collection over several days as in the chemical stool fat analysis is not necessary. The FATS test was carried out on 35 patients thought to be suffering from malassimilation syndrome and these results were compared to the chemically determined stool fat excretion as a reference method with the following results: The sensitivity of the FATS test for the detection of steatorrhea was 70.8%, the specificity 100%. The test has the same clinical value as other tests using radionuclide-marked bonds. As a quantitative parameter of fat excretion it is too inexact. Because of its low sensitivity it is no clinical alternative for chemical stool fat analysis. (TRV).

  16. Nanoassemblies containing a fluorouracil/zidovudine glyceryl prodrug with phospholipase A2-triggered drug release for cancer treatment.

    Jin, Yiguang; Yang, Fang; Du, Lina


    Secretory phospholipase A2 (sPLA2), which is overexpressed in many tumors, cleaves ester bonds at the sn-2 position of phospholipids. A PLA2-sensitive amphiphilic prodrug, 1-O-octadecyl-2-(5-fluorouracil)-N-acetyl-3-zidovudine-phosphorylglycerol (OFZG), was synthesized and used to prepare nanoassemblies through the injection of a mixture of OFZG/cholesterol/Tween 80 (2:1:0.1, mol:mol:mol) into water. Cholesterol and Tween 80 was incorporated into the OFZG monolayers at the air/water interface to yield nanoassemblies. The resulting nanoassemblies exhibited a narrow size distribution with a mean size of 77.8nm and were stable due to their high surface charges. The in vitro experiments showed that PLA2 degraded OFZG. The nanoassemblies exhibited higher anticancer activity than the parent drug 5-fluorouracil (5-FU) in COLO205, HT-28, and HCT-116 cells. The intravenous (i.v.) administration of the nanoassemblies into mice resulted in the rapid elimination of OFZG from the circulation and its distribution mainly in the liver, lung, spleen, and kidney. After their injection into tumor-bearing mice, the nanoassemblies exhibited anticancer efficiency comparable to that of 5-FU, even though the nanoassemblies contained concentrations of only 1/10 of the molar amount of 5-FU. The lessons learned from the study and methods for the design of PLA2-sensitive amphiphilic prodrugs are also discussed. Enzyme-sensitive amphiphilic combinatorial prodrugs and prodrug-loaded nanoassemblies may represent a new strategy for anticancer drug design.

  17. Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial

    Nøjgaard, Camilla; Hornum, Mads; Elkjaer, Margarita


    with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P

  18. A Prospective Randomized Trial of Diltiazem Gel and Glyceryl Trinitrate Ointment on Treatment of Chronic Anal Fissure

    M Akhondi-Meybodi


    Methods: This semi-experimental study consisted of sixty six outpatients (34 females and 32 males with chronic anal fissure, who referred to the gastroenterology clinic. Patients were randomly classified into two groups. Group A received GTN ointment (0.03%, whereas group B was treated with Diltiazem gel (2%. The treatment was administered twice daily for 8 weeks. Healing and side-effects were recorded to be compared after 8 weeks. Results: In group A, the anal fissure was thoroughly healed within 53.3% of patients, moderately healed for 6.7% of patients and not healed in 25.8% of patients. Moreover, side-effects were noted in 15(46.9% patients (P= 0.482. Two (6.2% patients had intolerable headache and discontinued the study, 11 (34.3% patients suffered from headache and 2 patients (6.2% were reported to have orthostatic hypotension. In group B, healing occurred in 21(67.7% out of 31 patients and 1 (3.2% case of headache was noted(P= 0.0001. Conclusion: The present study has demonstrated that topical diltiazem can be preferable to GTN owing to the absence of side-effects.

  19. Effect of ethylcellulose and propylene glycol on the controlled-release performance of glyceryl monooleate-mertronidazole periodontal gel.

    Sallam, Al-Sayed; Hamudi, Firas Falih; Khalil, Enam Ayoub


    Controlled-release metronidazole, mucoadhesive gel proposed as a drug-delivery system for periodontal application was developed and characterized. The system was based on a mixture of glycerylmonooleate (GMO) and ethylcellulose (EC). The mechanism of release depends: firstly, on the ability of GMO to form a viscous liquid crystalline mesophases and secondly on the solubilized EC to form a hydrophobic network when the mixture comes into contact with water resulting in sustaining the release of the drug. Ethylcellulose dissolved in GMO had a profound influence on the rate of drug release, reduced the initial drug release and prolonged the sustained release of metronidazole. Propylene glycol (PG) was added to increase the solubility of the drug and water was added with PG to control the viscosity. A controlled release formulation containing w/w, 20% metronidazole, 10% PG, 5% water and 65% GMO that contains 7% EC was found to be mucoadhesive, easily injectable at room temperature, and to follow Fickian diffusion release mechanism. When the drug loading was increased the drug release was accelerated, and the mechanism followed anomalous controlled-release mechanism. Stability studies indicated that the formulation should be stored at 4 °C in a dark place.

  20. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers

    Kruuse, C; Iversen, Helle Klingenberg; Jansen-Olesen, I


    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...

  1. Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7-36)) amide in C57BL/6J mice.

    Fujii, Yoshie; Osaki, Noriko; Hase, Tadashi; Shimotoyodome, Akira


    The widespread prevalence of diabetes, caused by impaired insulin secretion and insulin resistance, is now a worldwide health problem. Glucagon-like peptide 1 (GLP-1) is a major intestinal hormone that stimulates glucose-induced insulin secretion from β cells. Prolonged activation of the GLP-1 signal has been shown to attenuate diabetes in animals and human subjects. Therefore, GLP-1 secretagogues are attractive targets for the treatment of diabetes. Recent epidemiological studies have reported that an increase in daily coffee consumption lowers diabetes risk. The present study examined the hypothesis that the reduction in diabetes risk associated with coffee consumption may be mediated by the stimulation of GLP-1 release by coffee polyphenol extract (CPE). GLP-1 secretion by human enteroendocrine NCI-H716 cells was augmented in a dose-dependent manner by the addition of CPE, and was compatible with the increase in observed active GLP-1(7-36) amide levels in the portal blood after administration with CPE alone in mice. CPE increased intracellular cyclic AMP (cAMP) levels in a dose-dependent manner, but this was not mediated by G protein-coupled receptor 119 (GPR119). The oral administration of CPE increased diet (starch and glyceryl trioleate)-induced active GLP-1 secretion and decreased glucose-dependent insulinotropic polypeptide release. Although CPE administration did not affect diet-induced insulin secretion, it decreased postprandial hyperglycaemia, which indicates that higher GLP-1 levels after the ingestion of CPE may improve insulin sensitivity. We conclude that dietary coffee polyphenols augment gut-derived active GLP-1 secretion via the cAMP-dependent pathway, which may contribute to the reduced risk of type 2 diabetes associated with daily coffee consumption.

  2. Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function.

    Mack Correa, Mary Catherine; Mao, Guangru; Saad, Peter; Flach, Carol R; Mendelsohn, Richard; Walters, Russel M


    Plant-derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA-d34 ). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA-d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose-dependent manner, with the highest increase from treatment with pure OA. OA-d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA-d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions. © 2013. Johnson & Johnson Consumer Companies Inc.. Experimental Dermatology published by John Wiley & Sons Ltd.

  3. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enhancing agent.

    Traini, Enea; Bramanti, Vincenzo; Amenta, Francesco


    Cholinergic precursors have represented the first approach to counter cognitive impairment occurring in adultonset dementia disorders. These compounds were early leaved because their clinical efficacy was not clearly demonstrated. This is probably not true for some choline-containing phospholipids including choline alphoscerate. Choline alphoscerate increases the release of acetylcholine in rat hippocampus, facilitates learning and memory in experimental animals, improves brain transduction mechanisms and decreases age-dependent structural changes occurring in rat brain areas involved in learning and memory. The compound exerts neuroprotective effects in models of altered cholinergic neurotransmission and of brain vascular injury. In clinical studies choline alphoscerate improved memory and attention impairment, as well as affective and somatic symptoms in dementia disorders. An ongoing trial indicates that association between the acetylcholinesterase inhibitor donepezil and choline alphoscerate is accompanied by an improvement in several cognitive tests superior to that induced by donepezil alone. It is suggested that this association may represent a therapeutic option to prolong beneficial effects of cholinergic therapies in Alzheimer's disease patients with concomitant ischemic cerebrovascular disorders. In summary, choline alphoscerate has significant effects on cognitive function with a good safety profile and tolerability. Although limited both in terms of size of the samples investigated and of the length of treatment, preclinical and clinical results presented suggest that cognitive enhancing capabilities of choline alphoscerate merit of being further investigated in appropriate trials.

  4. Stable isotope-assisted LC-MS/MS monitoring of glyceryl trinitrate bioactivation in a cell culture model of nitrate tolerance.

    Axton, Elizabeth R; Hardardt, Elizabeth A; Stevens, Jan F


    The nitric oxide (NO) metabolites nitrite (NO2(-)) and nitrate (NO3(-)) can be quantified as an endpoint of endothelial function. We developed a LC-MS/MS method of measuring nitrite and nitrate isotopologues, which has a lower limit of quantification (LLOQ) of 1 nM. This method allows for isotopic labeling to differentiate newly formed nitrite and nitrate from nanomolar to micromolar background levels of nitrite and nitrate in biological matrices. This method utilizes 2,3-diaminonaphthalene (DAN) derivatization, which reacts with nitrite under acidic conditions to produce 2,3-naphthotriazole (NAT). NAT was chromatographically separated on a Shimadzu LC System with an Agilent Extend-C18 5 μm 2.1 × 150 mm column and detected using a multiple reaction monitoring (MRM) method on an ABSciex 3200 QTRAP mass spectrometer operated in positive mode. Mass spectrometry allows for the quantification of (14)N-NAT (m/z 170.1) and (15)N-NAT (m/z 171.1). Both nitrite and nitrate demonstrated a linear detector response (1 nM - 10 μM, 1 nM - 100 nM, respectively), and were unaffected by common interferences (Dulbecco's Modified Eagle Medium (DMEM), fetal bovine serum (FBS), phenol red, and NADPH). This method requires minimal sample preparation, making it ideal for most biological applications. We applied this method to develop a cell culture model to study the development of nitrate tolerance in human endothelial cells (EA.hy926).

  5. Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

    Asghar, Mohammed Sohail; Ashina, Messoud


    of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological......Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way...

  6. 亚硝酸盐是硝酸甘油在血中代谢的中间产物%Nitrite is an intermediate of glyceryl trinitrate metabolism in blood

    周和平; 田亚平; 贾兴旺



  7. Effects of glyceryl trinitrate on canine Oddi sphincter function after pancreas transplantation%三硝酸甘油对胰腺移植犬Oddi括约肌运动的影响

    李桂臣; 原春辉; 程颖; 刘永锋


    目的研究三硝酸甘油(GTN)对膀胱引流式犬胰腺移植后移植物Oddi括约肌(SO)功能的影响.方法对正常犬和膀胱引流式胰腺移植后犬应用GTN前后进行SO测压,并检测犬SO中环磷酸鸟苷(CGMP)水平.结果正常犬SO基础压为(18.5±2.8)mmHg(1 mmHg=1.33kPa),收缩频率为(9.7±1.5)次/分,收缩幅度为(47.1±5.5)mm Hg,动力指数为235.6±56.1.应用GTN后SO基础压、收缩频率、收缩幅度和动力指数分别显著降低为(8.1±2.4)mm Hg,(6.2±1.0)次/分,(21.1±4.0)mmHg和66.5±22.7,与用药前相比,差异有极显著性(P均<0.01).移植物SO基础压和收缩频率分别升高为(27.8±2.8)mmHg和(13.1±1.9)次/分,收缩幅度缩小为(8.3±1.8)mm Hg.移植犬应用GTN后,基础压、收缩频率和动力指数分别降低为(20.2±2.7)mm Hg,(7.5±1.4)次/分和98.8±28.5,与用药前相比,差异有显著性(P均<0.05).应用GTN后,正常犬和移植犬SO中CGMP水平分别为(86.5±15.5)pmol/g和(62.6±12.6)pmol/g,显著高于应用GTN前(P<0.01).结论GTN可能通过提高SO组织中CGMP水平抑制正常和移植后犬的SO运动.

  8. Effects and mechanisms of glyceryl trinitrate on alleviation of acetaminophen hepatotoxicity%硝酸甘油减轻对乙酰氨基酚肝毒性的作用与机制

    任利君; 弥曼; 宁养红; 李汾; 李新华


    目的:研究硝酸甘油(GTN)对对乙酰氨基酚(AP)肝毒性的影响与机制.方法:小鼠ip GTN 0.1~1.6 mg/kg.15 min后ip AP 300 mg/kg,6 h后测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST);GTN(1.6 mg/kg)预处理小鼠,测定AP半数致死量(LD50);荧光法测定肝蛋白S-亚硝基化水平;分光光度法测定肝谷氨酸脱氢酶(GDH)活性;S-亚硝基谷胱甘肽(GSNO)处理GDH纯酶,Saville-Griess法测定其S-亚硝基化水平,并观察对N-乙酰-P-苯醌亚胺(NAPQI)灭活GDH效应的影响.结果:GTN降低AP导致的ALT,AST升高,使AP对小鼠LD50由321 mg/kg上升至762 mg/kg;GTN引起肝蛋白S-亚硝基化水平升高,使AP对肝GDH的抑制作用完全消失;GSNO诱发GDH纯酶发生S-亚硝基化,且不影响酶活性,但修饰后的GDH不被NAPQI灭活.结论:GTN可减轻AP肝毒性,其机制与诱发肝蛋白巯基S-亚硝基化,减少NAPQI与蛋白(如GDH)巯基的共价结合有关.

  9. The character and mechanism of glyceryl trinatrate inhibiting coxsackievirus%硝酸甘油抗B组柯萨奇病毒的作用特点和机制

    李晓波; 曾明; 孙艳影; 史巧云; 钟照华; 田野; 谷鸿喜; 张凤民; 周昌伟


    目的研究硝酸甘油(GTN)抗柯萨奇B组3型病毒(CVB3)的作用特点和机制.方法比较先经GTN预处理及与GTN同时加入的两种处理方法相同滴度的病毒所引起的CPE抑制率的差异;分别测定并比较多次给予GTN及不同时间点给予GTN对CVB3感染的HeLa细胞组间的细胞病变效应抑制效果;测定GTN在HeLa细胞中不同时间点代谢产生的NO浓度, 并做NO浓度与不同时间点给予GTN的细胞病变效应抑制结果的相关性分析.结果预加GTN组与同时加GTN组经等量病毒攻击所引起的CPE无显著性差异(P>0.05);多次给药的组间CPE抑制率无显著性差异(P>0.05),但不同时间点给药的组间CPE抑制率具有显著差异(P<0.05),NO浓度与不同时间点给予GTN的细胞病变效应抑制结果呈正相关(r=0.97,P<0.01).结论 GTN是通过其代谢产物NO来发挥抗CVB3作用的.

  10. 硝酸甘油抑制Hela细胞生长繁殖机制研究%The studies on the inhibitory effect and mechanism of glyceryl trinitrate on Hela cells proliferation

    张阳东; 田亚平; 董矜; 汪德清


    目的研究硝酸甘油(GTN)对肿瘤细胞生长繁殖的影响及机制.方法以人宫颈癌细胞系(Hela细胞)为研究对象,用四甲基偶氮唑(MTT)法检测Hela细胞的活性;流式细胞仪检测bcl-2蛋白,细胞周期,细胞凋亡指数;比色法检测亚硝酸盐、还原型谷胱甘肽(GSH).结果 GTN代谢产生一氧化氮(NO)及亚硝酸盐,MTT试验显示Hela细胞活性明显降低;经0.175 mmol/L GTN处理后,Hela内GSH由(43.97±2.80) nmol/106降至(36.46±2.32) nmol/106细胞,细胞培养体系GSH由(71.68 ± 3.02) μmmol/L降至(58.38±0.81) μmol/L;bcl-2蛋白表达下降,细胞凋亡指数由1.47±0.03提高到2.72±0.089,使Hela细胞G2~M期所占比例由3.47±1.09增加至12.71±1.45,S期所占比例由45.955±4.66降至34.867±3.92.结论 GTN可抑制肿瘤细胞的生长繁殖,其机制与GTN代谢消耗GSH和产生NO有关.

  11. Studies on the inhibitory effects of glyceryl trinitrate on murine transplanted S180 tumors%硝酸甘油对移植性S180肿瘤的抑制作用及机制探索

    田亚平; 张阳东; 董矜; 姜辉


    目的:观察硝酸甘油(GTN)对小鼠移植性肿瘤的生长抑制作用及对动物代谢的影响.方法:将肉瘤180细胞接种到昆明小鼠腋窝皮下,分别用0.32 mg和0.16 mg的GTN灌胃,1/d,连续10 d,对照组给以生理盐水.10 d后处死动物,观察抑瘤率并眼眶取血计数白细胞,测定GSH、ALT、AST、Glu和Urea的变化.结果:GTN灌胃组能明显抑制小鼠S180实体瘤的生长,血液GSH和Urea明显降低,而Glu和AST水平明显升高,ALT未见明显变化.结论:GTN能够明显抑制小鼠移植性S180实体瘤的生长,并能改善荷瘤小鼠的生存质量.

  12. Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate.


    Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.

  13. Stability enhancement of curcumin by glyceryl monooleate/TPGS/chitosan lipid nanoparticles%单油酸甘油酯/TPGS/壳聚糖脂质纳米粒提高姜黄素稳定性的研究

    李来存; 付萌; 陈娟; 张建军; 高缘


    目的 制备载有姜黄素的单油酸甘油酯(GMO)/聚乙二醇1000维生素E琥珀酸酯(TPGS)/壳聚糖(CS)脂质纳米粒,考察该脂质纳米粒在提高药物稳定性方面的潜能.方法 采用乳化-高压均质法制备载有姜黄素的GMO/TPGS/CS脂质纳米粒,对该纳米粒进行粒径及分布、zeta电位、微观形态、物理稳定性、UV-Vis光谱学及体外释放动力学等表征.并以姜黄素水溶液为对照,测定该脂质纳米粒在高温、光照、强碱等条件下的稳定性.结果 该纳米粒为球形或类球形,平均粒径为(93.8±2.80)nm,多分散系数为(0.156±0.063),zeta电位为+(16.76±1.52) mV;有良好的物理稳定性;UV-Vis光谱显示,姜黄素可能通过疏水作用结合在纳米粒上,这使得药物产生缓释效果,符合Weibull方程.相比姜黄素水溶液,在高温、光照及强碱等强条件下,包封在纳米粒中的姜黄素降解程度显著减小.结论 本试验证明了结合使用GMO/TPGS/CS制备姜黄素脂质纳米粒,可显著提高姜黄素的稳定性.

  14. Encapsulation and retention of chelated-copper inside hydrophobic nanoparticles: Liquid cored nanoparticles show better retention than a solid core formulation.

    Hervella, Pablo; Parra, Elisa; Needham, David


    In the field of imaging, (18)F-fluorodeoxyglucose (FDG) PET imaging allows evaluation of glucose metabolism and is the most widely used imaging agent clinically for metastatic cancer. While it can certainly detect the metastatic disease, in order to provide a more fully "individualized medicine" strategy of detection and pharmaceutical treatment, what is needed are additional imaging nanoparticles that resemble the subsequently-administered nanoparticle drug delivery system itself. Both of these nanoparticles must also be able to take advantage of what may well be a limited EPR effect in human tumors, which in and of itself still needs to be characterized in the clinic. Administration of FDG, followed by a nanoparticle imaging agent, followed by a therapeutic nanoparticle would constitute such an "individualized medicine strategy", especially for anti-metastasis approaches. It is here that our endogenous-inspired nanoparticle strategies for imaging and therapeutics are focused on encapsulating and retaining imaging ions such as copper inside novel hydrophobic nanoparticles. In this paper, we describe a new approach to label the core of hydrophobic nanoparticles composed of Glyceryl Trioleate (Triolein) with copper using the hydrophobic chelator Octaethyl porphyrin (OEP). The research plan for this study was to (1) Formulate nanoparticles and control nanoparticle size using a modification of the solvent injection technique, named fast ethanol injection; (2) Chelate copper into the octaethyl porphyrin; (3) Encapsulate OEP-Cu in nanoparticles: the encapsulation efficiency of copper into liquid nanoparticles (LNP), solid nanoparticles (SNP) and phospholipid liposomes (PL) was evaluated by UV-Vis and atomic absorption spectroscopy; (4) Retain the encapsulated OEP-Cu in the liquid or solid cores of the nanoparticles in the presence of a lipid sink. (1) The size of the nanoparticles was found to be strongly dependent on the Reynolds number and the initial concentration of

  15. Characterization of lipase in reversed micelles formulated by Cibacron Blue F-3GA modified Span 85

    Zhang, Dong Hao; Guo, Zheng; Sun, Yan


    Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil...

  16. Medium- and long-chain triglycerides labeled with 13C: a comparison of oxidation after oral or parenteral administration in humans.

    Metges, C C; Wolfram, G


    The special physical properties of medium-chain triglycerides (MCT) result in some substantial differences in their metabolism compared to that of long-chain triglycerides (LCT). Administering MCT is of importance in enteral nutrition of patients with disturbances of fat digestion or lipoprotein lipase deficiency. Their use in parenteral nutrition is also of interest. The purpose of this study was to compare the rate of conversion of MCT and LCT to CO2 after parenteral or oral administration in humans. At 1-wk intervals, a liquid formula diet (418 kJ/h for 8 h) was given to five healthy volunteers following an overnight fast. Two hours after starting this, they were given either 100 mg [13C]trioctanoate or [13C]trioleate orally or parenterally. Excess 13C in breath carbon dioxide was analyzed by mass-spectrometry, and oxidation rates over 7.5 h were calculated. Oxidation rates for [13C]trioctanoate were on the average 34.7% after enteral and 31.0% after parenteral administration, and for [13C]trioleate, 25.3 and 24.9%, respectively (p less than 0.05, trioctanoate vs. trioleate). The results show that the oxidation of trioctanoate in healthy humans is greater both after oral and parenteral administration and increases more rapidly than that of [13C]trioleate.

  17. Advanced Design Linear Noise-Attenuating Earphone-Earcup System.


    were coated with each of the contaminants listed below. After the periods of time listed, they were again attached and the new "droop" measured. A...contains water, glycerin, glycol, stearate, beeswax , lanolin oil, sesame oil, glyceryl oleate, glyceryl stearate, isopropyl myristate, myristyl

  18. Solid lipid extrusion of sustained release dosage forms.

    Reitz, Claudia; Kleinebudde, Peter


    The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5) and glyceryl trimyristate (Dynasan 114), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 degrees C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 degrees C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.

  19. Catalytic performance of acidic ionic liquid-functionalized silica in biodiesel production

    Bin; Zhen; Qingze; Jiao; Qin; Wu; Hansheng; Li


    Acidic ionic liquid([BsAIm][OTf]) was immobilized on sulfhydryl-group-modified SiO2(MPS-SiO2) via free radical addition reaction. The[BsAIm][OTf] loading on acidic ionic liquid-functionalized silica([BsAIm][OTf]/SiO2) was controlled through tuning the sulfydryl(SH)content of MPS-SiO2. All the samples were characterized by FT-IR, elemental analysis, N2adsorption-desorption measurements and TGDTA. The catalytic performance of [BsAIm][OTf]/SiO2in the esterification of oleic acid and the transesterification of glycerol trioleate for biodiesel production was investigated. The results showed that with the increase of [BsAIm][OTf] loading on SiO2the specific surface area and pore volume of [BsAIm][OTf]/SiO2decreased, and the pore diameter of [BsAIm][OTf]/SiO2narrowed. In the esterificaiton of oleic acid, the oleic acid conversion increased with the increasing [BsAIm][OTf] loading. In the transesterification of glycerol trioleate, with the increasing[BsAIm][OTf] loading the glycerol trioleate conversion decreased and the selectivities to glycerol monooleate and methyl oleate increased.

  20. Inhibition of Listeria monocytogenes by fatty acids and monoglycerides.

    Wang, L. L.; Johnson, E. A.


    Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl m...

  1. 硝酸甘油对大鼠缺氧心肌细胞乙醛脱氢酶2 表达的影响%Effect of glyceryl trinitrate on expression of aldehyde dehydrogenase 2 in hypoxia-exposed rat cardiomyocytes

    张应花; 孙爱军; 文小军; 王克强; 邹云增; 葛均波


    目的 探讨硝酸甘油(GTN)对大鼠缺氧心肌细胞凋亡的影响及其相关机制,为阐明长期使用GTN导致心脏不良事件的发病机制提供依据.方法 利用心肌细胞缺氧模型,将缺氧的正常细胞作为对照组,测定GTN作用1~3 d时心肌细胞的凋亡率以及乙醛脱氢酶2(ALDH2)基因和蛋白的表达.结果 ①1、10、100μmol/L的GTN作用1 d的心肌细胞凋亡均显著少于对照组(P值均<0.05),作用2、3 d的细胞凋亡数均显著高于作用1 d时(P值均<0.05).由此确定GTN的作用浓度是1μmol/L,作用时间是2 d.②不同浓度GTN作用1~3 d,ALDH2基因表达与心肌细胞凋亡率呈负相关(r=-0.658,P=0.028).③1μmol/LGTN作用2 d时的ALDH2蛋白表达为1.35±0.16,显著低于对照组的1.66±0.22(P<0.05);作用2、3 d时的ALDH2蛋白表达分别为1.35±0.16和0.33±0.27,均较作用1 d时显著下降(P值均<0.05).结论 ①GTN作用不同时间所起的作用不同:作用1 d,为心肌保护作用;作用2~3 d能引起心肌细胞凋亡增加,缺乏心肌保护作用.②GTN使用后ALDH2基因表达变化与心肌细胞凋亡呈负相关,可能与ALDH2对缺氧心肌细胞有保护作用有关.③GTN作用2~3 d时缺氧心肌细胞ALDH2 mRNA和蛋白水平下调,可能与ALDH2消耗有关.

  2. Effect of Glyceryl Trinatrate and Isosorbide Dinitrate Against Replication of Coxsackievirus B3 in viva%硝酸甘油和硝酸异山梨酯抗柯萨奇B组3型病毒感染的体内实验研究

    孙艳影; 杜凤霞; 夏美玲; 孙艳; 钟照华


    目的 研究硝酸甘油(glyeeryl trinatrate,GTN)和硝酸异山梨酯(isosorbide dinitrate,ISDN)抗柯萨奇B组3型病毒(CVB3)的作用,为GTN和ISDN今后在抗CVB性心肌疾病的临床应用提供实验依据.方法 用HeLa细胞扩增并收获CVB3后,测定CVB3的半数组织培养感染剂量(TCID50),BALB/c小鼠腹腔注射5000 TCID50的CVB3,同时给予GTN和ISDN,14天后处死小鼠,取心脏做常规组织病理学检查.结果 用GTN、ISDN保护的小鼠心肌病理标本每视野(x100)病灶数明显低于病毒 对照组,GTN组为0.89±0.18,ISDN组为1.25±0.22.与病毒对照组差异显著(P<0.05).结论 GTN、ISDN等临床常用于抗心绞痛的硝酸酯类药物具有明确的抗CVB3感染BALB/c小鼠心肌细胞的作用.

  3. 油酸及单硝酸异山梨酯载入量对单油酸甘油酯液晶体系相图及体外释放的影响%Effect of oleic acid and isosorbide mononitrate loading on the phase diagrams and in vitro release profiles of glyceryl monooleate liquid crystalline system

    张星一; 马迪; 郑亚真; 许梁; 高缘


    考察油酸(OA)及单硝酸异山梨酯(ISMN)载入量对单油酸甘油酯(GMO)液晶体系相图及药物释放的影响.制备GMO/H2O,GMO/H2O/ISMN和GMO/H2O/OA 3种液晶体系的相图,考察了GMO的吸水行为及ISMN从GMO液晶载药体系的释药特性.结果表明,药物从GMO中的释放属于扩散释放,ISMN载入量的升高加快液晶体系的释药速率,而油酸载入量的增加使释药减慢.本研究为GMO液晶体系的载药及附加剂的使用提供了理论基础.

  4. Lipstick dermatitis due to C18 aliphatic compounds.

    Hayakawa, R; Matsunaga, K; Suzuki, M; Arima, Y; Ohkido, Y


    An 18-year-old girl developed cheilitis. She had a past history of lip cream dermatitis, but the cause was not found. Patch tests with 2 lipsticks were strongly positive. Tests with the ingredients were positive to 2 aliphatic compounds, glyceryl diisostearate and diisostearyl malate. Impurities in the materials were suspected as the cause. Analysis by gas chromatography detected 3 chemicals in glyceryl diisostearate and 1 in diisostearyl malate as impurities. Patch testing with the impurities and glyceryl monoisostearate 0.01% pet in glyceryl diisostearate and isostearyl alcohol 0.25% pet in diisostearyl malate were strongly positive. The characteristics common to the 2 chemicals were liquidity at room temperature, branched C18 aliphatic compound and primary alcohol. Chemicals lacking any of the above 3 features did not react.

  5. Shouldering the blame for impingement: the rotator cuff continuum

    dFaculty of Health Sciences, University of the Witwatersrand. *Corresponding author: Jarrad .... glyceryl trinitrate patches to the site of maximal tenderness is also supported by level 2 ... Omer Ilahi, MD [homepage on the. Internet]. 2011. c2014.

  6. 21 CFR 172.832 - Monoglyceride citrate.


    ... monooleate and its citric acid monoester manufactured by the reaction of glyceryl monooleate with citric acid... additive meets the following specifications: Acid number, 70-100. Total citric acid (free and combined),...

  7. Pharmacology of reflex blinks in the rat: a novel model for headache research.

    Jones, M G; Andreou, A P; McMahon, S B; Spanswick, D


    Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents. In anaesthetised rats the electromyogram associated with the reflex blink evoked by corneal airpuff was recorded. Rats were infused with glyceryl trinitrate, sumatriptan plus glyceryl trinitrate or vehicle control. Changes in the magnitude of the reflex blink-associated electromyogram following these treatments were measured. Glyceryl trinitrate potentiated the evoked reflex blink-associated EMG response from 2 h after infusion. That effect was abolished by simultaneous infusion of sumatriptan with glyceryl trinitrate. These results show that simple skin surface measurements of evoked electromyographic activity in the rat can reliably detect the evoked blink reflex that can be potentiated by nitric oxide donors. This novel model may be an effective tool for evaluating putative anti-migraine therapeutic agents.

  8. Preparation of Hemoglobin-Containing Microcapsules.


    was used in early work with the lecithin complexes, and in all the tests with EC and HESA. This procedure consists of emulsifying the aqueous Hb...mineral oil containing 0.4% lecithin (soybean) and 0.4% Span 85 (sorbitan trioleate, Atlas Chemicals) a W/O emulsifier . " Cool the emulsion in an ice...solution, pH 7 mixed with 0.l-mL Ringer Locke solution. The GA solution was either emulsified by * sonication in the lecithin solution and the emulsion

  9. A comprehensive model of anaerobic bioconversion of complex substrates to biogas

    Angelidaki, Irini; Ellegaard, Lars; Ahring, Birgitte Kiær


    .e., carbohydrates, lipids, and proteins, the concentration of intermediates such as volatile fatty acids and long-chain fatty acids, and important inorganic components, i.e., ammonia, phosphate, cations, and anions. This allows dynamic changes of the process during a shift of substrate composition to be simulated......) constitute the primary modulating factors in the model. The model was rested with success in lab-scale reactors codigesting manure with glycerol trioleate or manure with gelatin. Finally, the model was validated using results from a full-scale biogas plant codigesting manure together with a proteinous...

  10. Encapsulation and retention of chelated-copper inside hydrophobic nanoparticles

    Hervella, Pablo; Ortiz, Elisa Parra; Needham, David


    MOTIVATION: In the field of imaging, (18)F-fluorodeoxyglucose (FDG) PET imaging allows evaluation of glucose metabolism and is the most widely used imaging agent clinically for metastatic cancer. While it can certainly detect the metastatic disease, in order to provide a more fully "individualized...... Trioleate (Triolein) with copper using the hydrophobic chelator Octaethyl porphyrin (OEP). RESEARCH PLAN AND METHODS: The research plan for this study was to (1) Formulate nanoparticles and control nanoparticle size using a modification of the solvent injection technique, named fast ethanol injection; (2...

  11. Drug: D00515 [KEGG MEDICUS

    Full Text Available D00515 Drug Nitroglycerin (JP16/USP); Glyceryl trinitrate; Minitran (TN); Nitro-bid... affecting individual organs 21 Cardiovascular agents 214 Antihypertensives 2149 Others D00515 Nitroglycerin... (JP16/USP) 217 Vasodilators 2171 Coronary dilators D00515 Nitroglycerin (JP16/USP) Anatomical Therapeutic C...RAPY C01D VASODILATORS USED IN CARDIAC DISEASES C01DA Organic nitrates C01DA02 Glyceryl trinitrate D00515 Nitroglycerin...PICAL USE C05AE Muscle relaxants C05AE01 Glyceryl trinitrate D00515 Nitroglycerin (JP16/USP) USP drug classification [BR:br08302] Cardiovascular Agents Vasodilators, Direct-acting Arterial/Venous Nitroglycerin D00515 Nitroglycerin (JP16/USP) CAS: 55-63-0 PubChem: 7847581 DrugBank: DB00727 PDB-CCD: TNG LigandBox: D00515 NIKKAJI: J4.491A ATOM 15 1 C1c C 25.0868 -17.7109 2 C1b C

  12. Cluster headache: transcranial Doppler ultrasound and regional cerebral blood flow studies

    Dahl, A.; Russell, D.; Nyberg-Hansen, R.; Rootwelt, K. (Rikshospitalet, Oslo (Norway))


    Transcranial Doppler and rCBF examinations were carried out in 25 cluster headache patients. Spontaneous glyceryl trinitrate (nitroglycerin) provoked attacks were accompanied by a bilateral decrease in middle cerebral artery blood flow velocities. This decrease was more pronounced on the symptomatic side, but the difference did not reach statistical significance. Mean hemispheric blood flow and rCBF were within normal limits during provoked attacks and similar to those found when patients were attack-free. During cluster periods middle cerebral artery velocities were significantly higher on the symptomatic side. Glyceryl trinitrate caused a bilateral middle cerebral artery velocity decrease which was significantly greater on the symptomatic side. Attacks provoked by glyceryl trinitrate appeared to begin when the vasodilatory effect of this substance was received. 17 refs., 2 figs., 5 tabs.

  13. NO donors. Part 18: Bioactive metabolites of GTN and PETN--synthesis and vasorelaxant properties.

    Lange, Kathrin; Koenig, Andreas; Roegler, Carolin; Seeling, Andreas; Lehmann, Jochen


    The vasodilators glyceryl trinitrate (GTN) and pentaerythrityl tetranitrate (PETN) are supposed to be degraded in vivo to the lower nitrates PETriN, PEDN, PEMN, 1,2-GDN, 1,3-GDN, 1-GMN, and 2-GMN. We synthesized these bioactive metabolites as reference compounds for pharmacokinetic studies. The use of HPLC-methods for monitoring the stepwise reduction of PETN to lower nitrates and the syntheses of the glyceryl dinitrates proved advantageous. Furthermore, we measured the vasorelaxant properties of all metabolites by performing organ bath experiments with porcine pulmonary arteries. In general, the vasodilator potency increases with the number of nitrate moieties in the compound.

  14. Nitroglycerin-induced headache is not dependent on histamine release

    Iversen, Helle Klingenberg; Olesen, J


    The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric...

  15. Role of Ser102 and Ser104 as Regulators of cGMP Hydrolysis by PDE5A

    Carøe Nordgaard, Julie; Kruse, Lars Schack; Gammeltoft, Steen;


    -N-AS neuroblastoma cells as C-terminal fusions with green fluorescent protein. Transfected cells were treated with sildenafil, cilostazol, glyceryl trinitrate, calcitonin gene-related peptide (CGRP) or sumatriptan. PDE5A-GFP fusion proteins were localized in fixed cells by immunofluorescence and PDE activity...

  16. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies.

    Gaspar, Diana P; Faria, Vasco; Gonçalves, Lídia M D; Taboada, Pablo; Remuñán-López, Carmen; Almeida, António J


    Systemic administration of antitubercular drugs can be complicated by off-target toxicity to cells and tissues that are not infected by Mycobacterium tuberculosis . Delivery of antitubercular drugs via nanoparticles directly to the infected cells has the potential to maximize efficacy and minimize toxicity. The present work demonstrates the potential of solid lipid nanoparticles (SLN) as a delivery platform for rifabutin (RFB). Two different RFB-containing SLN formulations were produced using glyceryl dibehenate or glyceryl tristearate as lipid components. Full characterization was performed in terms of particle size, encapsulation and loading efficiency, morphology by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies. Physical stability was evaluated when formulations were stored at 5 ± 3°C and in the freeze-dried form. Formulations were stable throughout lyophilization without significant variations on physicochemical properties and RFB losses. The SLN showed to be able to endure harsh temperature conditions as demonstrated by dynamic light scattering (DLS). Release studies revealed that RFB was almost completely released from SLN. In vitro studies with THP1 cells differentiated in macrophages showing a nanoparticle uptake of 46 ± 3% and 26 ± 9% for glyceryl dibehenate and glyceryl tristearate SLN, respectively. Cell viability studies using relevant lung cell lines (A549 and Calu-3) revealed low cytotoxicity for the SLN, suggesting these could be new potential vehicles for pulmonary delivery of antitubercular drugs.

  17. Effekten af nitrogenoxiddonoren glyceryltrinitrat på humane smertetaerskler for tryk

    Thomsen, L L; Brennum, J; Iversen, Helle Klingenberg;


    The purpose of the present study was to examine the effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) on nociceptive thresholds in man. On two different study days twelve healthy subjects received a stair case infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min 20 min each dose...

  18. The effect of sodium nitroprusside on cerebral hemodynamics and headache in healthy subjects

    Guo, Song; Ashina, Messoud; Olesen, Jes;


    InvestigationSodium nitroprusside (SNP) is a powerful vasodilatory agent that, similarly to glyceryl trinitrate (GTN), releases nitric oxide (NO) but in contrast does not pass the blood-brain barrier. Nevertheless, it has already been used in animal models without any knowledge of its headache......-inducing agent with close similarities to headaches induced by GTN and probably without effect on intracerebral arteries....

  19. 46 CFR Table II to Part 150 - Grouping of Cargoes


    ... Kraft black liquor Kraft pulping liquors Mercaptobenzothiazol, sodium salt solution Potassium hydroxide... (C10-C20, saturated and unsaturated) phosphite Alkyl sulfonic acid ester of phenol Alkylaryl phosphate... Fatty acids (saturated, C14+) Glycerol polyalkoxylate Glyceryl triacetate Glycidyl ester of C10...

  20. Inconspicamide, New N-Acylated Serinol from the Marine Sponge Stelletta inconspicuqa

    Ueoka, R.; Fujita, T.; Iwashita, T.; van Soest, R.W.M.; Matsunaga, S.


    A new N-acylated serinol, inconspicamide (1), was isolated from the marine sponge, Stelletta inconspicua, together with a glyceryl ether (2). Their structures were determined on the basis of spectroscopic data and the modified Mosher analysis. They exhibited moderate cytotoxic activity against HeLa

  1. Nitroglycerin kan give hypertension

    Mørup, Peter; Levinsen, Tine Holbæk; Hovind, Peter


    Hg. The conclusion was that her response was a paradoxical response to glycerylnitrate, orthostatism and a pathological response to massage of the carotid artery. This is the third reported case on paradoxical hypertension induced by glyceryl nitrates. It is speculated that dysfunction of the cerebral bloodflow...

  2. Nitric oxide is a key molecule in migraine and other vascular headaches

    Olesen, J; Thomsen, L L; Iversen, Helle Klingenberg


    Nitric oxide (NO) may play a key role in migraine and other vascular headaches since glyceryl trinitrate (a donor of NO) and histamine (which probably activates endothelial NO formation) both cause a pulsating dose-dependent headache with several migrainous characteristics. At relatively high doses...

  3. Optimization of biomethanation focusing on high ammonia loaded processes

    Wang, Han

    , could theoretically mitigate the ammonia inhibition problem (Angelidaki et al., 1999). Therefore, the effect of co-digestion of cattle manure with lipids (i.e. glycerol trioleate (GTO)) under high ammonia levels (5 g NH4+-N·L-1) in anaerobic continuous stirred tank (CSTR) reactors (RGTO) was assessed....... Additionally, for comparison purposes, a soluble carbohydrate (i.e. glucose) was also used as a co-substrate in an identical CSTR reactor (RGLU). At 5 g NH4+-N·L-1, relative methane production of RGTO and RGLU, was 10.5% and 41% compared to the expected uninhibited production, respectively. At the same time...... control reactor (RCTL), only fed with manure, reached 32.7% compared to the uninhibited basis production. Therefore, the hypothesis that the co-digestion of manure with lipids could alleviate the ammonia inhibition was not supported by the results. However, an “ammonia-LCFA synergetic inhibitory effect...

  4. Anaerobic digestion of manure and mixture of manure with lipids: biogas reactor performance and microbial community analysis

    Mladenovska, Zuzana; Dabrowski, Slawomir; Ahring, Birgitte Kiær


    the activity of acetotrophic methanogens was uniformly distributed in all fractions. When digesting manure and lipids, an enhanced methanogenesis was detected both for particles > 200 mum and the 50-200 mum fraction. The molecular methods -temperature gradient gel electrophoresis (TGGE), cloning library......Anaerobic digestion of cattle manure and a mixture of cattle manure with glycerol trioleate (GTO) was studied in lab-scale, continuously stirred tank reactors (CSTR) operated at 37degreesC. The reactor. codigesting manure and lipids exhibited a significantly higher specific methane yield...... and a higher removal of VS than the reactor treating manure. Microbial population analysis done by cultivation - most probable number (MPN) test and specific methanogenic activity (SMA) measurement, revealed higher MPN and increased SMA of methanogenic populations of biomass from the reactor codigesting manure...

  5. Ammonia - LCFA synergetic co-inhibition effect in manure-based continuous biomethanation process

    Wang, Han; Fotidis, Ioannis; Angelidaki, Irini


    uninhibited production, respectively. At the same time control reactor (RCTL), only fed with manure, reached 32.7% compared to the uninhibited basis production. Therefore, it seems that using lipids to counteract the ammonia effect in CSTR reactors creates an “ammonia–LCFA (long chain fatty acids) synergetic......In the current study it has been hypothesized that, when organic loading of an anaerobic reactor is increased, the additional cell biomass biosynthesis would capture more ammonia nitrogen and thereby reduce the ammonia toxicity. Therefore, the alleviation of the toxicity of high ammonia levels...... using lipids (glycerol trioleate-GTO) or carbohydrates (glucose-GLU) as co-substrates in manure-based thermophilic continuous stirred-tank reactors (RGTO and RGLU, respectively) was tested. At 5 g NH4+-N L−1, relative methane production of RGTO and RGLU, was 10.5% and 41% compared to the expected...

  6. Novel Neolignan from Penthorum chinense


    A new neolignan(7'E)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one(1)was isolated from the whole plants of Penthorum chinense Pursh,along with lupeol (2), betulinic acid(3),glyceryl monopalmitate(4),β-sitosterol(5),palmitic acid(6),ursolic acid(7),2β,3β,23-trihydroxy-urs-12-ene-28-oic acid(8),glyceryl monolaurate(9),scopoletin(10).luteolin(16),β-daucosterol(17),quercetin(18),1-O-(β-D-glucopyranosyl)-(2S,2'R,3R,4E,8E)-2-(2'-hydroxyhexadecanoy-lamino)-4,8-octdecadiene-1,3-dool (19),gallic acid (20),pinocembrin-7-O-β-D-glucoside(21),and quercetin-3-O-β-D-glucoside(22).The structures of these compounds ware elucidated on the basis of chemical and spectral evidence.

  7. Meta-analysis: Nitroglycerin for prevention of post-ERCP pancreatitis

    Bang, Ulrich Christian; Nøjgaard, C; Andersen, P K


    BACKGROUND: Acute pancreatitis after ERCP is a severe side effect. AIM: To evaluate the preventive effect of nitroglycerin on post-ERCP pancreatitis by a meta-analysis of randomized clinical studies. METHODS: We searched on Pubmed, Embase, Cochrane Library and all abstracts presented at Digestive...... Disease Week and United European Gastrointestinal Week from 2004 to 2008. We used the MeSH terms 'pancreatitis' together (AND) with the terms: 'glyceryl trinitrate', 'glyceryl dinitrate', 'isosorbide dinitrate' or 'nitroglycerin'. RESULTS: Five clinical studies evaluating the incidence of post......-ERCP pancreatitis after administration of nitroglycerin were identified. Meta-analysis including all five studies showed a relative risk (RR) of 0.61 (95% CI; 0.44, 0.86) with the number needed to treat (NNT) of 26 (95% CI: 16, 82). Three studies evaluated nitroglycerin administered by a dermal patch reaching...

  8. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS)

    Bath, Philip M W; Woodhouse, Lisa; Scutt, Polly


    BACKGROUND: High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs......·91-1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90-1·22; p=0·55). INTERPRETATION: In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show...... to lower their blood pressure. METHODS: In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140-220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day...

  9. 布洛芬固体脂质微颗粒的制备及其晶体构型研究%Preparation and Crystal Modification of Ibuprofen-Loaded Solid Lipid Microparticles

    龙春霞; 章莉娟; 钱宇


    An emulsion-congealing technique is used to prepare solid lipid microparticles (SLM) containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% (relative to lipid only). Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.

  10. Transesterification of triglycerides using nitrogen-functionalized carbon nanotubes.

    Villa, Alberto; Tessonnier, Jean-Philippe; Majoulet, Olivier; Su, Dang Sheng; Schlögl, Robert


    Nitrogen-functionalized carbon nanotubes were synthesized by grafting amino groups to the surface of the nanotubes. The nanotubes exhibited promising results in the base-catalyzed liquid phase transesterification of glyceryl tributyrate with methanol, which is a model reaction for the production of biodiesel. The concentration of the active sites and the reaction parameters, such as temperature and glyceryl tributyrate to methanol ratio, were shown to significantly affect catalytic performance. The grafting technique employed allowed for design and control of the active sites. As a consequence, it was possible to design a nitrogen-functionalized carbon nanotube catalyst with a few strong, basic groups. This might be of interest for carbohydrate conversion reactions where strong basic sites are required but the pH of the solution should remain mild to avoid the degradation of the reactants and/or products.

  11. Scent gland constituents of the Middle American burrowing python, Loxocemus bicolor (Serpentes: Loxocemidae).

    Schulze, Thies; Weldon, Paul J; Schulz, Stefan


    Analysis by gas chromatography/mass spectrometry of the scent gland secretions of male and female Middle American burrowing pythons (Loxocemus bicolor) revealed the presence of over 300 components including cholesterol, fatty acids, glyceryl monoalkyl ethers, and alcohols. The fatty acids, over 100 of which were identified, constitute most of the compounds in the secretions and show the greatest structural diversity. They include saturated and unsaturated, unbranched and mono-, di-, and trimethyl-branched compounds ranging in carbon-chain length from 13 to 24. The glyceryl monoethers possess saturated or unsaturated, straight or methyl-branched alkyl chains ranging in carbon-chain length from 13 to 24. Alcohols, which have not previously been reported from the scent glands, possess straight, chiefly saturated carbon chains ranging in length from 13 to 24. Sex or individual differences in secretion composition were not observed. Compounds in the scent gland secretions of L. bicolor may deter offending arthropods, such as ants.

  12. Identification de filtres solaires dérivés de l'acide para-aminobenzoique par spectroscopie RMN et par CPG/SM.

    Masse, M O; Delporte, C; Bervelt, E


    Gas chromatography coupled with mass spectrometry and protonic nuclear magnetic resonance used directly or on fractions obtained by preparative thin layer chromatography, allow identification of the main molecule in commercial samples of PABA (Cas RN 150-13-0), PEG-25 PABA (Cas RN 116242-27-4), glyceryl PABA (Cas RN136-44-7), ethyl dihydroxypropyl PABA (Cas RN 58882-17-0) or octyl dimethyl PABA (Cas RN 21245-02-3).

  13. Alternate Sources for Propellant Ingredients.


    ricinoleates (castor oil) Cobalt naphthenate Shellac Elba solvent Ni troform Ammonium oxalate Sodium barbiturate Cateqory 6: Materials with...with the compound. MAPO: Category 1, P, K. Triz(2- methyl -l-aziridinyl) phosphine oxide (MAPO) is used as a crosslinking agent for polymers containing...elements, ranging from 0.001% tin to 0.03% for molybdenum. Glyceryl Mono-and Tri- ricinoleates : Category 5, S, F. These esters are found in castor oil

  14. Investigation of Different Lipid Based Materials as Matrices Designed to Control the Release of a Hydrophobic Drug

    Inderbir Singh; Pradeep Kumar; Nisha Rani; Vikas Rana


    The present study was designed to evaluate the effect of different hydrophobic materials and their loading level on the release profile of etoricoxib, a model lipophilic drug, from matrix systems. Matrix tablets of the drug were prepared using compritol, precirol, glyceryl monostearate, cetostearyl alcohol and eudragit as release retarding agents by direct compression process. The resulting monolithic tablets were found to have optimum hardness, uniform thickness, high content uniformity and ...

  15. Direct Synthesis of ESBO Derivatives-18O Labelled with Dioxirane

    Stefano La Tegola


    Full Text Available This work addresses a new approach developed in our laboratory, consisting in the application of isolated dimethyldioxirane (DDO, 1a labelled with 18O for synthesis of epoxidized glyceryl linoleate (Gly-LLL, 2. We expect that this work could contribute in improving analytical methods for the determination of epoxidized soybean oil (ESBO in complex food matrices by adopting an 18O-labelled-epoxidized triacylglycerol as an internal standard.

  16. Impact of Anti-tacking Agents on Properties of Gas-Entrapped Membrane and Effervescent Floating Tablets


    Tackiness caused by the gas-entrapped membrane (Eudragit®RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the...

  17. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin


    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a...

  18. Preparation and characterization of loperamide-loaded Dynasan 114 solid lipid nanoparticles for increased oral absorption in the treatment of diarrhea

    Lili Wei; Yunfang Yang; Kun Shi; Jun Wu; Wei Zhao; Jingxin Mo


    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a...

  19. Towards a reliable animal model of migraine

    Olesen, Jes; Jansen-Olesen, Inger


    The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

  20. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    J. Sedef Göçmen


    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  1. In vitro study on sustained release capsule formulation of acetazolamide.

    Pandey, V P; Kannan, K; Manavalan, R; Desai, N


    In the present study formulation of sustained release capsule of acetazolamide 250 mg was tried using nonpareil seeds. Nonpareil seeds were coated with drug, polyvinylpyrrolidone, glyceryl monostearate, microcrystalline wax, and glyceryl distearate either individually or in combination to achieve sustained release capsule 250 mg. In successful formulation 20% drug coated pellets and 80% wax coated pellets were taken. Wax coated pellets for successful formulation contained coating of microcrystalline wax and glyceryl distearate on drug coated pellets of the same concentration of 1.6% w/w. Successful formulated sustained release capsule 250 mg of acetazolamide was compared in in vitro study with theoretical sustained release formulation suggested by wagner and one marketed sustained release capsule 250 mg. Formulated capsule showed result superior to or on par with marketed capsule. For successful formulation pellets were filled in '1' size hard gelatin capsule and stability study was carried out in hot air over at room temperature and 45 degrees C for 5 weeks. The formulation was found stable in respect of drug content and release rate.

  2. Inhibition of Listeria monocytogenes by fatty acids and monoglycerides.

    Wang, L L; Johnson, E A


    Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl monopalmitate were not inhibitory at 200 micrograms/ml. The bactericidal activity in brain heart infusion broth was higher at pH 5 than at pH 6. In whole milk and skim milk, K-conjugated linoleic acid was bacteriostatic and prolonged the lag phase especially at 4 degrees C. Monolaurin inactivated L. monocytogenes in skim milk at 4 degrees C, but was less inhibitory at 23 degrees C. Monolaurin did not inhibit L. monocytogenes in whole milk because of the higher fat content. Other fatty acids tested were not effective in whole or skim milk. Our results suggest that K-conjugated linoleic acids or monolaurin could be used as an inhibitory agent against L. monocytogenes in dairy foods.

  3. The development of Cutina lipogels and gel microemulsion for topical administration of fluconazole.

    El Laithy, H M; El-Shaboury, K M F


    The influence of the vehicle on the release and permeation of fluconazole, a topical antifungal drug dissolved in Jojoba oil was evaluated. Series of Cutina lipogels (Cutina CPA [cetyl palmitate], CBS [mixture of glyceryl stearate, cetearyl alcohol, cetyl palmitate, and cocoglycerides], MD [glyceryl stearate], and GMS [glyceryl monostearate]) in different concentrations as well as gel microemulsion were prepared. In-vitro drug release in Sorensen's citrate buffer (pH 5.5) and permeation through the excised skin of hairless mice, using a modified Franz diffusion cell, were performed. The rheological behavior and the apparent viscosity values for different gel bases were measured before and after storage under freezing conditions at -4 degrees C and were taken as measures for stability of network structure. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved. The results of in vitro drug release and its percutaneous absorption showed that the highest values from gel microemulsion were assured. The rheological behavior of the prepared systems showed pseudoplastic (shear-thinning) flow indicating structural breakdown of the existing intermolecular interactions between polymeric chains. Moreover, the stability study revealed no significant difference between viscosity before and after storage for different formulae except for CPA Cutina lipogel (using analysis of variance [ANOVA] test at level of significance.05). The antifungal activity of fluconazole showed the widest zone of inhibition with gel microemulsion. The gel microemulsion is an excellent vehicle for fluconazole topical drug delivery.

  4. Uptake, transport and peroral absorption of fatty glyceride grafted chitosan copolymer-enoxaparin nanocomplexes: influence of glyceride chain length.

    Wang, Linlin; Sun, Yujiao; Shi, Chenjun; Li, Liang; Guan, Jian; Zhang, Xin; Ni, Rui; Duan, Xiaopin; Li, Yaping; Mao, Shirui


    The objective of this paper is to elucidate the influence of fatty glyceride chain length in chitosan copolymers on the peroral absorption of enoxaparin. First of all, a series of chitosan copolymers with glyceryl monocaprylate (GM8), glyceryl monolaurate (GM12) and glyceryl monostearate (GM18) as the hydrophobic part were synthesized. The structure of the copolymers was characterized using proton nuclear magnetic resonance. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that all the copolymers were non-toxic. Enoxaparin nanocomplexes were prepared by self-assembly. Mucoadhesion of the nanocomplexes was characterized using the mucin particle method. Nanocomplex uptake and transport were quantified in Caco-2 cells and cellular localization was visualized by confocal laser scanning microscopy. Enoxaparin uptake was enhanced by nanocomplex formation, and was dependent on incubation time, concentration, temperature and glyceride chain length. The GM8 grafted chitosan-enoxaparin nanocomplex exhibited the strongest bioadhesion and the best uptake and transport in both cell culture and in vivo absorption in rats. The uptake mechanism was assumed to be adsorptive endocytosis via clathrin- and caveolae-mediated processes. In conclusion, oral absorption of enoxaparin can be further enhanced by using GM8 grafted chitosan copolymer as the carrier to form nanocomplexes.

  5. Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants.

    Shamma, Rehab Nabil; Basalious, Emad B; Shoukri, Raguia


    Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, beeswax, glyceryl tripalmitate (GTP) and glyceryl tristearate) were evaluated for the preparation of matrix pellets. A D-optimal design was employed for the optimization and to explore the effect of drug loading (X(1)), concentration of lipophilic surfactant (X(2)), concentration of co-surfactant (X(3)) and wax type (X(4)) on the release extent of the drug from matrix pellets. The entrapment efficiency (Y(1)), pellet diameter (Y(2)), and the percentage drug released at given times were selected as dependent variables. Results revealed a significant impact of all independent variables on drug release from the formulated pellets. The lipophilic surfactant significantly increased both the entrapment efficiency and the in vitro drug release and significantly decreased the pellet size. The optimized BH-loaded pellets were composed of 19.95% drug loading, 9.95% Span(®) 80 (surfactant), 0.25% Capmul(®) (co-surfactant) using glyceryl tripalmitate as a matrix former. The release profiles of the drug from hard gelatin capsule containing optimized pellets equivalent to 32 mg BH was similar to that of target release model for once-daily administration based on similarity factor. It could be concluded that a promising once-daily capsule containing sustained release pellets of BH was successfully designed.

  6. Endocannabinoids and their oxygenation by cyclo-oxygenases, lipoxygenases and other oxygenases.

    Urquhart, P; Nicolaou, A; Woodward, D F


    The naturally occurring mammalian endocannabinoids possess biological attributes that extend beyond interaction with cannabinoid receptors. These extended biological properties are the result of oxidative metabolism of the principal mammalian endocannabinoids arachidonoyl ethanolamide (anandamide; A-EA) and 2-arachidonoylglycerol (2-AG). Both endocannabinoids are oxidized by cyclo-oxygenase-2 (COX-2), but not by COX-1, to a series of prostaglandin derivatives (PGs) with quite different biological properties from those of the parent substrates. PG ethanolamides (prostamides, PG-EAs) and PG glyceryl esters (PG-Gs) are not only pharmacologically distinct from their parent endocannabinoids, they are distinct from the corresponding acidic PGs, and are differentiated from each other. Ethanolamides and glyceryl esters of the major prostanoids PGD2, PGE2, PGF2α, and PGI2 are formed by the various PG synthases, and thromboxane ethanolamides and glyceryl esters are not similarly produced. COX-2 is also of interest by virtue of its corollary central role in modulating endocannabinoid tone, providing a new therapeutic approach for treating pain and anxiety. Other major oxidative conversion pathways are provided for both A-EA and 2-AG by several lipoxygenases (LOXs), resulting in the formation of numerous hydroxyl metabolites. These do not necessarily represent inactivation pathways for endocannabinoids but may mimic or modulate the endocannabinoids or even display alternative pharmacology. Similarly, A-EA and 2-AG may be oxidized by P450 enzymes. Again a very diverse number of metabolites are formed, with either cannabinoid-like biological properties or an introduction of disparate pharmacology. The biological activity of epoxy and hydroxyl derivatives of the endocannabinoids remains to be fully elucidated. This review attempts to consolidate and compare the findings obtained to date in an increasingly important research area. This article is part of a Special Issue entitled

  7. Short-chain flavor ester synthesis in organic media by an E. coli whole-cell biocatalyst expressing a newly characterized heterologous lipase.

    Guillaume Brault

    Full Text Available Short-chain aliphatic esters are small volatile molecules that produce fruity and pleasant aromas and flavors. Most of these esters are artificially produced or extracted from natural sources at high cost. It is, however, possible to 'naturally' produce these molecules using biocatalysts such as lipases and esterases. A gene coding for a newly uncovered lipase was isolated from a previous metagenomic study and cloned into E. coli BL21 (DE3 for overexpression using the pET16b plasmid. Using this recombinant strain as a whole-cell biocatalyst, short chain esters were efficiently synthesized by transesterification and esterification reactions in organic media. The recombinant lipase (LipIAF5-2 showed good affinity toward glyceryl trioctanoate and the highest conversion yields were obtained for the transesterification of glyceryl triacetate with methanol. Using a simple cetyl-trimethylammonium bromide pretreatment increased the synthetic activity by a six-fold factor and the whole-cell biocatalyst showed the highest activity at 40°C with a relatively high water content of 10% (w/w. The whole-cell biocatalyst showed excellent tolerance to alcohol and short-chain fatty acid denaturation. Substrate affinity was equally effective with all primary alcohols tested as acyl acceptors, with a slight preference for methanol. The best transesterification conversion of 50 mmol glyceryl triacetate into isoamyl acetate (banana fragrance provided near 100% yield after 24 hours using 10% biocatalyst loading (w/w in a fluidized bed reactor, allowing recycling of the biocatalyst up to five times. These results show promising potential for an industrial approach aimed at the biosynthesis of short-chain esters, namely for natural flavor and fragrance production in micro-aqueous media.

  8. Effects of Zhengtian Pills on Migraine Headache in Rats via Transient Receptor Potential Vanilloid 1

    Jun-hua Sun; Ke-zhu Wang; Hui Fu; Zhi Dai; Fei-fei Pu; Song Yin; Tian-xiu Qian; Xin-min Liu; Xiao-ying Wang


    Objective To investigate the effects and molecular mechanism of Zhengtian Pills(ZTP) on migraine headache. Methods All rats were randomly divided into control, positive control, migraine model, low- and high-dose ZTP groups, and glyceryl trinitrate was injected to induce migraine headache. The time of ears turning red, frequency of scratching head, climbing the cage, and head-twitching were used to evaluate rat behaviors. After 10 d administration of ZTP, the expression levels of transient receptor potential vanilloid 1(TRPV1) both in cortex and hippocampus were determined by Western blotting. Results After 2 min of glyceryl trinitrate injection, rats showed headache phenomena that parallels the clinical symptoms of migraine, which peaked in 30 min, and lasted for 60 min. Frequency of head-twitching and numbers of scratching head in glyceryl trinitrate(GTN) group were significantly increased. In contrast, after ZTP(1.08 g/kg, ig) treatment, the numbers of scratching head with fore-limb, hind-limb and the frequency of head-twitching were significantly decreased. Flunarizine(FLU) and low-dose ZTP(0.54 g/kg) also showed a trend to decrease the numbers of scratching head and head-twitching frequency, but no significant difference. Besides, ZTP significantly decreased the up-regulated TRPV1 protein expression level both in cortex and hippocampus. Conclusion The present study shows that ZTP could significantly improve the migraine symptoms of headache in rats and TRPV1 might be one of the important molecular mechanisms. This is the first report about the effect of ZTP on TRPV1 protein expression level both in cortex and hippocampus of rats.

  9. Short-chain flavor ester synthesis in organic media by an E. coli whole-cell biocatalyst expressing a newly characterized heterologous lipase.

    Brault, Guillaume; Shareck, François; Hurtubise, Yves; Lépine, François; Doucet, Nicolas


    Short-chain aliphatic esters are small volatile molecules that produce fruity and pleasant aromas and flavors. Most of these esters are artificially produced or extracted from natural sources at high cost. It is, however, possible to 'naturally' produce these molecules using biocatalysts such as lipases and esterases. A gene coding for a newly uncovered lipase was isolated from a previous metagenomic study and cloned into E. coli BL21 (DE3) for overexpression using the pET16b plasmid. Using this recombinant strain as a whole-cell biocatalyst, short chain esters were efficiently synthesized by transesterification and esterification reactions in organic media. The recombinant lipase (LipIAF5-2) showed good affinity toward glyceryl trioctanoate and the highest conversion yields were obtained for the transesterification of glyceryl triacetate with methanol. Using a simple cetyl-trimethylammonium bromide pretreatment increased the synthetic activity by a six-fold factor and the whole-cell biocatalyst showed the highest activity at 40°C with a relatively high water content of 10% (w/w). The whole-cell biocatalyst showed excellent tolerance to alcohol and short-chain fatty acid denaturation. Substrate affinity was equally effective with all primary alcohols tested as acyl acceptors, with a slight preference for methanol. The best transesterification conversion of 50 mmol glyceryl triacetate into isoamyl acetate (banana fragrance) provided near 100% yield after 24 hours using 10% biocatalyst loading (w/w) in a fluidized bed reactor, allowing recycling of the biocatalyst up to five times. These results show promising potential for an industrial approach aimed at the biosynthesis of short-chain esters, namely for natural flavor and fragrance production in micro-aqueous media.

  10. Optimized mixed oils remarkably reduce the amount of surfactants in microemulsions without affecting oral bioavailability of ibuprofen by simultaneously enlarging microemulsion areas and enhancing drug solubility.

    Chen, Yizhen; Tuo, Jue; Huang, Huizhi; Liu, Dan; You, Xiuhua; Mai, Jialuo; Song, Jiaqi; Xie, Yanqi; Wu, Chuanbin; Hu, Haiyan


    The toxicity and irritation associated with high amounts of surfactants restrict the extensive utilization of microemulsions. To address these shortcomings, employing mixed oils to enlarge microemulsion areas therefore reducing surfactant contents is a promising strategy. However, what kinds of mixed oils are more efficient in enlarging microemulsion areas still remains unclear. In this research, we found that the chain length and degree of unsaturation of oils play a key role in enlarging microemulsion areas. The combination of moderate chain saturated oil caprylic/capric triglyceride (GTCC) with long chain unsaturated oil glycerol trioleate significantly increased the microemulsion areas. Solubility of ibuprofen in the mixed oils was unexpectedly and remarkably increased (almost 300mg/mL) compared with that (around 100mg/mL) of the single oil (GTCC), which also resulted in greatly increased solubility of ibuprofen in mixed oils-containing microemulsions. By optimizing the mixed oil formulation, the absolute amount of surfactant in drug-loaded microemulsions was reduced but increased drug oral bioavailability in rats was maintained. It could be concluded that the combined use of moderate chain oils and long chain unsaturated oils could not only acquire enlarged microemulsion areas but also enhanced drug solubility, therefore doubly reducing surfactant amount, which is extremely beneficial for developing safe microemulsions.

  11. Crystallization kinetics of cocoa butter in the presence of sorbitan esters.

    Sonwai, Sopark; Podchong, Pawitchaya; Rousseau, Dérick


    Cocoa butter crystallization in the presence of sorbitan mono- and triesters or canola oil was investigated. Solid-state surfactant esters accelerated early-stage cocoa butter solidification while suppressing later growth. Sorbitan tristearate showed the strongest effect, followed by sorbitan monostearate and sorbitan monopalmitate. Liquid-state surfactants suppressed cocoa butter crystallization at all time points, with sorbitan trioleate showing a stronger effect than sorbitan monooleate, which behaved in a similar fashion to canola oil. Via DSC, the palmitic and stearic-based surfactants only associated with cocoa butter's high-melting fraction, with the oleic acid-based surfactants and canola oil showing little influence. All sorbitan esters had little effect on polymorphism, whereas canola oil accelerated the form II-to-III-to-IV transition. The palmitic and stearic-based surfactants greatly reduced cocoa butter crystal size whereas the oleic acid-based surfactants and canola showed no notable effect. Overall, sorbitan esters impacted cocoa butter crystallization kinetics, though this depended on surfactant structure and concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Palm oil derived trimethylolpropane triesters synthetic lubricants and usage in industrial metalworking fluid.

    Chang, Teck-Sin; Yunus, Robiah; Rashid, Umer; Choong, Thomas S Y; Awang Biak, Dayang Radiah; Syam, Azhari M


    Trimethylolpropane triesters are biodegradable synthetic lubricant base oil alternative to mineral oils, polyalphaolefins and diesters. These oils can be produced from trimethylolpropane (TMP) and fatty acid methyl esters via chemical or enzymatic catalyzed synthesis methods. In the present study, a commercial palm oil derived winter grade biodiesel (ME18) was evaluated as a viable and sustainable methyl ester source for the synthesis of high oleic trimethylolpropane triesters (HO-TMPTE). ME18 has fatty acid profile containing 86.8% oleic acid, 8.7% linoleic acid with the remaining minor concentration of palmitic acid, stearic acid and linolenic acid. It's high oleic property makes it superior to produce synthetic lubricant base oil that fulfills both the good low temperature property as well as good oxidative stability. The synthetic base oil produced had a viscosity of 44.3 mm(2)/s at 40°C meeting the needs for ISO 46 oils. It also exhibited an excellent viscosity index of 219 that is higher than some other commercial brands of trimethylolpropane trioleate. Properties of base oil such as cloud point, density, acid value, demulsibility and soap content were also examined. The oil was then used in the formulation of tapping oil and appraised in term of adaptability, stability and field test performance.

  13. Physicochemical Properties and Evaluation of Microemulsion Systems for Transdermal Delivery of Meloxicam


    Microemulsion systems, composed of water, isopropyl myristate (IPM), polyoxyethylene sorbitan trioleate (Tween 85 ), and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug( meloxicam). The purpose of this study was to investigate the physicochemical properties of the tested microemulsion and to find the correlation between the physicochemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio (Km =1:1) was constructed by titration at 20℃, and the five formulations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85, 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.

  14. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar


    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.

  15. Secondary oil recovery process. [two separate surfactant slugs

    Fallgatter, W.S.


    Oil recovery by two separate surfactant slugs is greater than for either one alone. One slug contains a surfactant(s) in either oil or water. The other slug contains surfactant(s) in thickened water. The surfactants are sodium petroleum sulfonate (Promor SS20), polyoxyethylene sorbitan trioleate (Tween 85), lauric acid diethanolamide (Trepoline L), and sodium tridecyl sulfate polyglycol ether (Trepenol S30T). The thickener is carboxymethyl cellulose (Hercules CMC 70-S Medium thickener) or polyvinyl alcohol (Du Pont Elvanol 50-42). Consolidated sandstone cores were flooded with water, followed with Hawes crude, and finally salt water (5 percent sodium chloride) which recovered about 67 percent of the crude. A maximum of 27.5 percent of the residual oil was recovered by surfactant(s) in oil or water followed by fresh water, then surfactant(s) plus thickener in water followed by fresh water. Either surfactant slug may be injected first. Individually, each of the surfactant slugs can recover from about 3 to 11 percent less residual oil than their total recovery when used consecutively.

  16. New Enzyme Inhibitory Constituents from Tribulus longipetalus

    Muhammad Akram Naveed


    Full Text Available Normal and reversed phasechromatographic purification of the chloroform soluble fraction of the methanolic extract of Tribulus longipetalus led to the isolation of a new tyramine amide, longipetalamide (1, two new benzocoumarins, longipetalasin A (8-n-propyl-threo-1 ¢ S ,2 ¢ S -dihydroxy-5-methoxy-5a,9a-benzocoumarin; 2 and B (8-n-propyl-threo-1 ¢ S ,2 ¢ S -dihydroxy-5,10-dimethoxy-5a,9a-benzocoumarin; 3 together with 1,2,3-propantriyl trioleate (4, crotamide A (5, stigmasterol (6, (25S-5α-furustan-22-methoxy-3β,26-diol (7, neotigogenin (8, tigogenin (9, methyl 4-hydroxyphenyl acetate (10 and 2-O-methylinositol (11. All the isolates (1-11 were characterized by using UV, IR, 1D- ( 1H and 13C, 2D-NMR (HSQC, HMBC, COSY spectroscopy, mass spectrometry (EI-MS, HR-EI-MS, FAB-MS, HR-FAB-MS and in comparison with the data reported in literature. The compounds 1-11 were evaluated for their enzyme inhibition studies against α-glucosidase, lipoxygenase (LOX, acetylcholinesterase (AChE and butyrylcholinesterase (BChE enzymes and found that 2 and 3 were the significant inhibitors of enzyme α-glucosidase with IC 50 values 94.17 ± 0.09 and 85.65 ± 0.08 µM, respectively.

  17. The role of lipids in activated sludge floc formation

    Anna Liza Kretzschmar


    Full Text Available Activated sludge is widely used to treat municipal and industrial wastewater globally and the formation of activated sludge flocculates (flocs underpins the ability to separate sludge from treated water. Despite the importance of activated sludge flocs to human civilization there have been precious few attempts to rationally design fit for purpose flocs using a bottom-up approach based on a solid scientific foundation. Recently we have been developing experimental models for activated sludge floc formation based on the colonization and consumption of particulate organic matter (chitin and cellulose. In this study we lay the foundation for investigation of activated sludge floc formation based on biofilm formation around spheres of the lipid glycerol trioleate (GT that form spontaneously when GT is introduced into activated sludge incubations. Sludge biomass was observed to associate tightly with the lipid spheres. An increase in extracellular lipase activity was associated with a decrease in size of the colonized lipid spheres over a 25 day incubation. Bacterial community composition shifted from predominantly Betaproteobacteria to Alphaproteobacteria in GT treated sludge. Four activated sludge bacteria were isolated from lipid spheres and two of them were shown to produce AHL like quorum sensing signal activity, suggesting quorum sensing may play a role in lipid spheres colonization and biodegradation in activated sludge. The development of this experimental model of activated sludge floc formation lays the foundation for rational production of flocs for wastewater treatment using lipids as floc nuclei and further development of the flocculate life-cycle concept.

  18. Ammonia-LCFA synergetic co-inhibition effect in manure-based continuous biomethanation process.

    Wang, Han; Fotidis, Ioannis A; Angelidaki, Irini


    In the current study it has been hypothesized that, when organic loading of an anaerobic reactor is increased, the additional cell biomass biosynthesis would capture more ammonia nitrogen and thereby reduce the ammonia toxicity. Therefore, the alleviation of the toxicity of high ammonia levels using lipids (glycerol trioleate-GTO) or carbohydrates (glucose-GLU) as co-substrates in manure-based thermophilic continuous stirred-tank reactors (R(GTO) and R(GLU), respectively) was tested. At 5gNH4(+)-NL(-1), relative methane production of R(GTO) and R(GLU), was 10.5% and 41% compared to the expected uninhibited production, respectively. At the same time control reactor (R(CTL)), only fed with manure, reached 32.7% compared to the uninhibited basis production. Therefore, it seems that using lipids to counteract the ammonia effect in CSTR reactors creates an "ammonia-LCFA (long chain fatty acids) synergetic co-inhibition" effect. Moreover, co-digestion with glucose in R(GLU) was more robust to ammonia toxicity compared to R(CTL). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects

    Kruuse, Christina; Thomsen, Lars Lykke; Jacobsen, Torsten Bjørn


    , and regional cerebral blood flow in the perfusion area of the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and xenon inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasound. Blood pressure and heart rate were recorded......Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics...

  20. Prolonged release matrix pellets prepared by melt pelletization. I. Process variables

    Thomsen, L.J.; Schaefer, T.; Sonnergaard, Jørn


    A melt pelletization process was investigated in an 8 litre laboratory scale high shear mixer using a formulation with paracetamol, glyceryl monostearate 40-50, and microcrystalline wax. The effects of jacket temperature, product temperature during massing, product load, massing time and impeller...... speed were investigated by means of factorially designed experiments. The maximum yield of pellets in the range of 500-1400 μm was found to approx. 90%. For process conditions preventing deposition of moist mass, the process was found to be reproducible. Impeller speed and massing time were found...

  1. Coexisting typical migraine in familial hemiplegic migraine

    Hansen, Jakob Møller; Olesen, Jes; Ashina, Messoud


    In contrast to patients with migraine with aura (MA) and migraine without aura (MO), most patients with familial hemiplegic migraine (FHM) do not report migraine-like attacks after pharmacologic provocation with glyceryl trinitrate (GTN), a donor of nitric oxide. In the present study, we examined...... patients with FHM without known gene mutations and hypothesized that 1) GTN would cause more migraine-like attacks in patients with FHM compared to controls, and 2) GTN would cause more migraine attacks in patients with FHM with coexisting MA or MO compared to the pure FHM phenotype....

  2. Aquivion Perfluorosulfonic Superacid as an Efficient Pickering Interfacial Catalyst for the Hydrolysis of Triglycerides.

    Shi, Hui; Fan, Zhaoyu; Hong, Bing; Pera-Titus, Marc


    Rational design of the surface properties of heterogeneous catalysts can boost the interfacial activity in biphasic reactions through the generation of Pickering emulsions. This concept, termed Pickering interfacial catalysis (PIC), has shown promising credentials in acid-catalyzed transesterification, ester hydrolysis, acetalization, etherification, and alkylation reactions. PIC has now been applied to the efficient, solvent-free hydrolysis of the triglyceride glyceryl trilaurate to lauric acid, catalyzed by Aquivion perfluorosulfonic superacid at mild conditions (100 °C and ambient pressure). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Renal cortical and medullary blood flow responses to altered NO-availability in humans

    Damkjaer, Mads; Vafaee, Manoucher; Møller, Michael Lehd;


    of one voxel were eliminated stepwise from the external surface of the VOI ('voxel peeling'), and the blood flow subsequently determined in each new, reduced VOI. Blood flow in the shrinking volumes of interest (VOIs) decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood...... flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ±0.17 ml·(g·min)(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ±0.18 ml·(g·min)(-1) (p...

  4. Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach.

    Patil, Ganesh B; Patil, Nandkishor D; Deshmukh, Prashant K; Patil, Pravin O; Bari, Sanjay B


    Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR.

  5. Index to FAA Office of Aerospace Medicine Reports


    pyrogen-induced hyperpyrexia in man. 64-9 Freud SL: Duration of spiral aftereffect as a function of retinal size, retinal place, and hemiretinal transfer...AD618588 64-10 Freud SL: Duration as a measure of the spiral aftereffect. AD618589 64-11 Pinkerson AL, Kot PA, Knowlan DM: Effect of glyceryl...mate- rial. II. AD456670 64-17 Freud SL: The physiological locus of the spiral aftereffect. AD611881 64-18 Melton CE Jr: Physiological recordings from

  6. Coexisting typical migraine in familial hemiplegic migraine

    Hansen, Jakob Møller; Thomsen, Lise Lykke; Olesen, Jes


    In contrast to patients with migraine with aura (MA) and migraine without aura (MO), most patients with familial hemiplegic migraine (FHM) do not report migraine-like attacks after pharmacologic provocation with glyceryl trinitrate (GTN), a donor of nitric oxide. In the present study, we examined...... patients with FHM without known gene mutations and hypothesized that 1) GTN would cause more migraine-like attacks in patients with FHM compared to controls, and 2) GTN would cause more migraine attacks in patients with FHM with coexisting MA or MO compared to the pure FHM phenotype....

  7. Nitric Oxide Modulation of Low-Frequency Oscillations in Cortical Vessels in FHM - a NIRS Study

    Schytz, Henrik W; Hansen, Jakob M; Phillip, Dorte


    Background.- The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical...... of the GTN infusion. Results.- GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P...

  8. An evaluation of acute hydrogen sulfide poisoning in rats through serum metabolomics based on gas chromatography-mass spectrometry.

    Zhang, Meiling; Deng, Mingjie; Ma, Jianshe; Wang, Xianqin


    Hydrogen sulfide (H2S) is the second leading cause of toxin-related deaths in the operational site. Its main target organs of toxic effects are the central nervous system and respiratory system. In this study, we developed a serum metabonomic method, based on gas chromatography-mass spectrometry (GC/MS), to evaluate the effect of acute poisoning by hydrogen sulfide on rats. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA), revealed that acute hydrogen sulfide poisoning induced metabolic perturbations. Compared to the control group, the level of urea, glucose, glyceryl stearate in rat serum of the poisoning group increased after two hours, and the level of glucose, docosahexaenoic acid, glyceryl stearate and arachidonic acid in rat serum of the poisoning group increased after 48 h, while the L-valine, galactose, L-tyrosine levels decreased. Our results indicate that metabonomic methods based on GC/MS may be useful to elucidate acute hydrogen sulfide poisoning through the exploration of biomarkers.

  9. Mycosporine-like Amino Acids and Other Phytochemicals Directly Detected by High-Resolution NMR on Klamath (Aphanizomenon flos-aquae) Blue-Green Algae.

    Righi, Valeria; Parenti, Francesca; Schenetti, Luisa; Mucci, Adele


    This study describes for the first time the use of high-resolution nuclear magnetic resonance (NMR) on Klamath (Aphanizomenon flos-aquae, AFA) blue-green algae directly on powder suspension. These algae are considered to be a "superfood", due to their complete nutritional profile that has proved to have important therapeutic effects. The main advantage of NMR spectroscopy is that it permits the detection of a number of metabolites all at once. The Klamath alga metabolome was revealed to be quite complex, and the most peculiar phytochemicals that can be detected directly on algae by NMR are mycosporine-like amino acids (porphyra-334, P334; shinorine, Shi) and low molecular weight glycosides (glyceryl β-d-galactopyranoside, GalpG; glyceryl 6-amino-6-deoxy-α-d-glucopyranoside, ADG), all compounds with a high nutraceutical value. The presence of cis-3,4-DhLys was revealed for the first time. This molecule could be involved in the anticancer properties ascribed to AFA.

  10. Identification of an emulsifier and conditions for preparing stable nanoemulsions containing the antioxidant astaxanthin.

    Kim, D-M; Hyun, S-S; Yun, P; Lee, C-H; Byun, S-Y


    In this study, oil-in-water nanoemulsions of astaxanthin were prepared by high-pressure homogenization. The influence of emulsifying conditions including emulsifier type, concentration, passing time, astaxanthin concentration and coantioxidants were optimized. The stabilities of nanoemulsions were measured using zetasizer, FF-SEM, TEM, colorimeter and particle size analyzer. The mean diameter of the dispersed particles containing astaxanthin ranged from 160 to 190 nm. The size distribution was unimodal and extended from 100 to 200 nm. The nanoemulsions prepared with glyceryl citrate/lactate/linoleate/oleate (glyceryl ester) had smaller particle size and narrower size distribution than the emulsion prepared with hydrogenated lecithin. Stable incorporation of astaxanthin in nanoemulsion was performed and checked using HPLC, FF-SEM and TEM. The nanoemulsion was not significantly affected during storage under light and thermal condition for one month indicating that the nanoemulsion had a zeta potential of less than -41 mV, indicating a stable colloid. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  11. Formulation of ranitidine pellets by extrusion-spheronization with little or no microcrystalline cellulose.

    Basit, A W; Newton, J M; Lacey, L F


    The present study was concerned with the feasibility of formulating ranitidine into pellets with a range of alternative excipients in place of microcrystalline cellulose (MCC). Eight ranitidine formulations employing two or more of the excipients lactose, barium sulfate, glyceryl monostearate, and MCC were processed by extrusion-spheronization, and characterized according to a series of physico-mechanical and dissolution criteria. Formulations containing lactose produced unsatisfactory pellets of wide size distribution and irregular shape, whereas formulations incorporating barium sulfate and glyceryl monostearate with or without MCC resulted in relatively spherical pellets of narrow size distribution and good mechanical properties. Ranitidine release was found to be rapid and virtually complete within 15 min, regardless of the pellet formulation. A direct relationship was observed between the concentration of MCC in the formulation and the properties of the pellets. In general, the higher the concentration of MCC, the rounder, stronger, and less friable the pellets. However, even pellets without MCC were also successfully prepared with a superior size distribution and shape over those with MCC. Overall, these results confirm that ranitidine can be formulated into pellet dosage forms with little or no MCC by the extrusion-spheronization process.

  12. Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: Biophysical characterization and inclusion of lipophilic dietary supplements

    Koynova, Rumiana; Tihova, Mariana (OSU); (Biopharma)


    Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipid liposome formulations can encapsulate up to 20-30 wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.

  13. Release of Methane from Bering Sea Sediments During the Last Glacial Period

    Mea Cook; Lloyd Keigwin


    Several lines of evidence suggest that during times of elevated methane flux the sulfate-methane transition zone (SMTZ) was positioned near the sediment-water interface. We studied two cores (from 700 m and 1457 m water depth) from the Umnak Plateau region. Anomalously low d13C and high d18O in benthic and planktonic foraminifera in these cores are the consequence of diagenetic overgrowths of authigenic carbonates. There are multiple layers of authigenic-carbonate-rich sediment in these cores, and the stable isotope compositions of the carbonates are consistent with those formed during anaerobic oxidation of methane (AOM). The carbonate-rich layers are associated with biomarkers produced by methane-oxidizing archaea, archaeol and glyceryl dibiphytanyl glyceryl tetraether (GDGT). The d13C of the archaeol and certain GDGTs are isotopically depleted. These carbonate- and AOM-biomarker-rich layers were emplaced in the SMTZ during episodes when there was a high flux of methane or methane-rich fluids upward in the sediment column. The sediment methane in the Umnak Plateau region appears to have been very dynamic during the glacial period, and interacted with the ocean-atmosphere system at millennial time scales. The upper-most carbonate-rich layers are in radiocarbon-dated sediment deposited during interstitials 2 and 3, 28-20 ka, and may be associated with the climate warming during this time.

  14. Dissimilarities between methylene blue and cyanide on relaxation and cyclic GMP formation in endothelium-intact intrapulmonary artery caused by nitrogen oxide-containing vasodilators and acetylcholine

    Ignarro, L.J.; Harbison, R.G.; Wood, K.S.; Kadowitz, P.J.


    The objective of the present study was to ascertain whether cyanide shares the properties of methylene blue as a selective inhibitor of vascular smooth muscle relaxation elicited by agents that stimulate the formation of cyclic GMP. Experiments were performed with endothelium-intact rings prepared from bovine intrapulmonary artery. Methylene blue, a good inhibitor of soluble guanylate cyclase, antagonized both arterial relaxation and cyclic GMP accumulation in response to sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine and acetylcholine. In contrast, cyanide inhibited only the responses to sodium nitroprusside. Increasing concentrations of methylene blue depressed resting arterial levels of cyclic GMP and caused slowly developing but marked contractions whereas cyanide was without effect. Contractile responses to phenylephrine, potassium and U46619 were potentiated by methylene blue but not by cyanide. Preincubation of dilute solutions of cyanide containing sodium nitroprusside in oxygenated Krebs' buffer at 37 degrees C for 15 min before addition to bath chambers depressed relaxation and cyclic GMP accumulation caused by sodium nitroprusside markedly. Similar treatment of glyceryl trinitrate, however, failed to alter its effects in arterial rings. A chemical inactivation of sodium nitroprusside by cyanide appears to account for the specific inhibitory action of cyanide on arterial responses to sodium nitroprusside. This study indicates clearly that cyanide does not share the properties of methylene blue as an inhibitor of arterial relaxation elicited by vasodilators that stimulate cyclic GMP formation.

  15. Nitric oxide-related drug targets in headache

    Olesen, Jes


    SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called del......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so......-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human...

  16. Development and characterization of lipid microparticles as a drug carrier for somatostatin.

    Reithmeier, H; Herrmann, J; Göpferich, A


    Somatostatin, a therapeutic peptide with a high therapeutical potential but a very short biological half-live was encapsulated within microparticles by a modified solvent evaporation method and a melt dispersion method without the use of organic solvent. As the use of synthetic polymer matrix materials often goes along with detrimental effects on incorporated peptides, we investigated the potential of physiological lipids such as glyceryl tripalmitate (Dynasan 116) as an alternative matrix material. The two preparation methods were evaluated with respect to surface topography, particle size distribution, encapsulation efficiency, in-vitro release behavior and modification of the resulting microparticles. Microparticles with a suitable particle size distribution for i.m. or s.c. injection could be prepared with both methods. The encapsulation efficiency of the peptide into glyceryl tripalmitate microparticles was substantially influenced by the preparation method and the physical state of the peptide to be incorporated. The melt dispersion technique and the incorporation of the drug as an aqueous solution gave the best results with actual drug loadings up to 9% and an encapsulation efficiency of approximately 90%. Microparticles prepared by the melt dispersion technique crystallized in the unstable alpha-modification. The peptide was released almost continuously over 10 days with no burst effect, 20-30% of the incorporated somatostatin was not released in the monitored time period.

  17. Microbial diversity of cold-seep sediments in Sagami Bay, Japan, as determined by 16S rRNA gene and lipid analyses.

    Fang, Jiasong; Shizuka, Arakawa; Kato, Chiaki; Schouten, Stefan


    Microbial communities in Calyptogena sediment and microbial mats of Sagami Bay, Japan, were characterized using 16S rRNA gene sequencing and lipid biomarker analysis. Characterization of 16S rRNA gene isolated from these samples suggested a predominance of bacterial phylotypes related to Gammaproteobacteria (57-64%) and Deltaproteobacteria (27-29%). The Epsilonproteobacteria commonly found in cold seeps and hydrothermal vents were only detected in the microbial mat sample. Significantly different archaeal phylotypes were found in Calyptogena sediment and microbial mats; the former contained only Crenarchaeota clones (100% of the total archaeal clones) and the latter exclusively Euryarchaeota clones, including the anaerobic oxidation of methane archaeal groups ANME-2a and ANME-2c. Many of these lineages are as yet uncultured and undescribed groups of bacteria and archaea. Phospholipid fatty acid analysis suggested the presence of sulphate-reducing and sulphur-oxidizing bacteria. Results of intact glyceryl dialkyl glyceryl tetraether lipid analysis indicated the presence of nonthermophilic marine planktonic archaea. These results suggest that the microbial community in the Sagami Bay seep site is distinct from previously characterized cold-seep environments.

  18. Effects of different nonionic surfactants on in vitro fermentation characteristics of cereal straws.

    Cong, Z H; Tang, S X; Tan, Z L; Sun, Z H; Zhou, C S; Han, X F; Wang, M; Ren, G P


    The effects of 3 nonionic surfactants (NIS), including alkyl polyglucoside (APG), sorbitan trioleate (Span85), and polyoxyethylene sorbitan monostearate (Tween80), on in vitro fermentation characteristics of maize stover, rice straw, and wheat straw were examined using an in vitro gas production technique. Four levels each of APG, Span85, and Tween80 [0, 0.02, 0.05, and 0.1% (vol/vol) of incubation solution] were tested in a 4 x 4 x 4 factorial arrangement. The NIS generally increased the in vitro maximal gas production (A), but decreased the lag time of cereal straws. The effects of NIS on the rate of gas production (B) were related to the surfactant type and fermented substrate. The NIS generally increased IVDMD and in vitro OM disappearance (IVOMD) of cereal straws, but responses were dose dependent. The NIS increased total VFA concentration of in vitro fermentation supernatant for maize stover and wheat straw, but decreased total VFA concentration for rice straw. The effects of NIS on the molar proportions of acetate, propionate, and butyrate were dependent on the dose and type of NIS and on fermented substrate. Several interactive effects were noted between or among 3 surfactants (APG, Span85, and Tween80) on in vitro gas production variables, IVD-MD, IVOMD, and VFA for each straw; the optimal combinations of 2 or 3 types of NIS were determined according to the responses of IVDMD and IVOMD to NIS addition. The results of this study suggest that NIS may improve in vitro fermentation of low quality roughages and have potential application as feed additives in ruminant production.

  19. Pterodon emarginatus oleoresin-based nanoemulsion as a promising tool for Culex quinquefasciatus (Diptera: Culicidae) control.

    Oliveira, Anna E M F M; Duarte, Jonatas L; Cruz, Rodrigo A S; Souto, Raimundo N P; Ferreira, Ricardo M A; Peniche, Taires; da Conceição, Edemilson C; de Oliveira, Leandra A R; Faustino, Silvia M M; Florentino, Alexandro C; Carvalho, José C T; Fernandes, Caio P


    Preparation of nanoformulations using natural products as bioactive substances is considered very promising for innovative larvicidal agents. On this context, oil in water nanoemulsions develop a main role, since they satisfactorily disperse poor-water soluble substances, such as herbal oils, in aqueous media. Pterodon emarginatus, popularly known as sucupira, has a promising bioactive oleoresin. However, to our knowledge, no previous studies were carried out to evaluate its potential against Culex quinquefasciatus, the main vector of the tropical neglected disease called lymphatic filariasis or elephantiasis. Thus, we aimed to investigate influence of different pairs of surfactants in nanoemulsion formation and investigate if a sucupira oleoresin-based nanoemulsion has promising larvicidal activity against this C. quinquefasciatus. We also evaluated morphological alteration, possible mechanism of insecticidal action and ecotoxicity of the nanoemulsion against a non-target organism. Among the different pairs of surfactants that were tested, nanoemulsions obtained with polysorbate 80/sorbitan monooleate and polysorbate 80/sorbitan trioleate presented smallest mean droplet size just afterwards preparation, respectively 151.0 ± 2.252 and 160.7 ± 1.493 nm. They presented high negative zeta potential values, low polydispersity index (algae Chlorella vulgaris at low concentration (25 mg/L). Our results suggest that optimal nanoemulsions may be prepared with different surfactants using a low cost and low energy simple method. Moreover, this prototype proved to be effective against C. quinquefasciatus, being considered an ecofriendly novel nanoproduct that can be useful in integrated control programs of vector control.

  20. Development of terbinafine solid lipid nanoparticles as a topical delivery system

    Chen Y-C


    Full Text Available Ying-Chen Chen,1* Der-Zen Liu,2* Jun-Jen Liu,3 Tsung-Wei Chang,1 Hsiu-O Ho,1 Ming-Thau Sheu,1,4 1School of Pharmacy, College of Pharmacy, 2Graduate Institute of Biomedical Materials and Engineering, 3School of Medical Laboratory Science and Biotechnology, 4Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*Ying-Chen Chen and Der-Zen Liu contributed equally in the preparation of this manuscript.Abstract: To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB, solid lipid nanoparticles (SLNs with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS, glyceryl behenate (Compritol® 888; Gattefossé, and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® OnceTM (Novartis Pharmaceuticals, in the stratum corneum (SC, viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a <5% lipid phase and >50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1 formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® OnceTM, whereas the amount of TB of the dermis

  1. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation

    Soliman Mahmoud L


    Full Text Available Abstract Background Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression. Methods In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively. Results We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9, histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein

  2. Liquid Crystalline Nanoparticles as an Ophthalmic Delivery System for Tetrandrine: Development, Characterization, and In Vitro and In Vivo Evaluation

    Liu, Rui; Wang, Shuangshuang; Fang, Shiming; Wang, Jialu; Chen, Jingjing; Huang, Xingguo; He, Xin; Liu, Changxiao


    The purpose of this study was to develop novel liquid crystalline nanoparticles (LCNPs) that display improved pre-ocular residence time and ocular bioavailability and that can be used as an ophthalmic delivery system for tetrandrine (TET). The delivery system consisted of three primary components, including glyceryl monoolein, poloxamer 407, and water, and two secondary components, including Gelucire 44/14 and amphipathic octadecyl-quaternized carboxymethyl chitosan. The amount of TET, the amount of glyceryl monoolein, and the ratio of poloxamer 407 to glyceryl monoolein were selected as the factors that were used to optimize the dependent variables, which included encapsulation efficiency and drug loading. A three-factor, five-level central composite design was constructed to optimize the formulation. TET-loaded LCNPs (TET-LCNPs) were characterized to determine their particle size, zeta potential, entrapment efficiency, drug loading capacity, particle morphology, inner crystalline structure, and in vitro drug release profile. Corneal permeation in excised rabbit corneas was evaluated. Pre-ocular retention was determined using a noninvasive fluorescence imaging system. Finally, pharmacokinetic study in the aqueous humor was performed by microdialysis technique. The optimal formulation had a mean particle size of 170.0 ± 13.34 nm, a homogeneous distribution with polydispersity index of 0.166 ± 0.02, a positive surface charge with a zeta potential of 29.3 ± 1.25 mV, a high entrapment efficiency of 95.46 ± 4.13 %, and a drug loading rate of 1.63 ± 0.07 %. Transmission electron microscopy showed spherical particles that had smooth surfaces. Small-angle X-ray scattering profiles revealed an inverted hexagonal phase. The in vitro release assays showed a sustained drug release profile. A corneal permeation study showed that the apparent permeability coefficient of the optimal formulation was 2.03-fold higher than that of the TET solution. Pre-ocular retention

  3. The Japan Flavour and Fragrance Materials Association's (JFFMA) safety assessment of acetal food flavouring substances uniquely used in Japan.

    Okamura, Hiroyuki; Abe, Hajime; Hasegawa-Baba, Yasuko; Saito, Kenji; Sekiya, Fumiko; Hayashi, Shim-Mo; Mirokuji, Yoshiharu; Maruyama, Shinpei; Ono, Atsushi; Nakajima, Madoka; Degawa, Masakuni; Ozawa, Shogo; Shibutani, Makoto; Maitani, Tamio


    Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on five acetal flavouring substances uniquely used in Japan: acetaldehyde 2,3-butanediol acetal, acetoin dimethyl acetal, hexanal dibutyl acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal. As no genotoxicity study data were available in the literature, all five substances had no chemical structural alerts predicting genotoxicity. Using Cramer's classification, acetoin dimethyl acetal and hexanal dibutyl acetal were categorised as class I, and acetaldehyde 2,3-butanediol acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal as class III. The estimated daily intakes for all five substances were within the range of 1.45-6.53 µg/person/day using the method of maximised survey-derived intake based on the annual production data in Japan from 2001, 2005, 2008 and 2010, and 156-720 µg/person/day using the single-portion exposure technique (SPET), based on the average use levels in standard portion sizes of flavoured foods. The daily intakes of the two class I substances were below the threshold of toxicological concern (TTC) - 1800 μg/person/day. The daily intakes of the three class III substances exceeded the TTC (90 μg/person/day). Two of these, acetaldehyde 2,3-butanediol acetal and hexanal glyceryl acetal, were expected to be metabolised into endogenous products after ingestion. For 4-methyl-2-pentanone propyleneglycol acetal, one of its metabolites was not expected to be metabolised into endogenous products. However, its daily intake level, based on the estimated intake calculated by the SPET method, was about 1/15 000th of the no observed effect level. It was thus concluded that all five substances raised no safety concerns when used for flavouring foods at the currently estimated intake levels. While no information on in vitro and in vivo toxicity for all five substances was available

  4. Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

    El-Salamouni, Noha S; Farid, Ragwa M; El-Kamel, Amal H; El-Gamal, Safaa S


    Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations.

  5. Prednisolone reduces nitric oxide-induced migraine

    Tfelt-Hansen, P; Daugaard, D; Lassen, L H


    BACKGROUND AND PURPOSE: Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN. METHODS: In this double-blind, randomized and placebo-controlled, crossover...... study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN (0.5 ug/kg/min). One hour after the GTN-infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out...... a headache diary every hour for 12 h. There were two equal primary efficacy end-points: frequency of delayed migraine and intensity of delayed headache. RESULTS: Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four...

  6. A new natural naphtho[1,2-b]furan from the leaves of Cassia fistula.

    Wang, Li-Qin; Tang, Zheng-Rong; Mu, Wei-Hua; Kou, Jun-Feng; He, Dong-Yang


    A new naphtho[1,2-b]furan, 2,9-dihydroxy-7-methoxy-4-methylnaphtha[1,2-b]furan-3(2H)-one (1), along with 10 known compounds vanillic acid (2), naringenin (3), glyceryl-1-tetracosanoate (4), moracin J (5), 1,3,8-trihydroxyanthraquinone (6), esculetin (7), mauritianin (8), kaempferol 3-neohesperidoside (9), β-sitosterol (10), and β-daucosterol (11), was isolated from the leaves of Cassia fistula. The structure of the new compound was determined by NMR and X-ray analysis. Compounds 1, 3, 5-9 were isolated from this plant for the first time. The naphtha[1,2-b]furan was firstly isolated from the natural resources.

  7. Reaksi Antara Gliserol dan o-Metoksi Fenol Dalam Suasana Basa dan Asam Sebagai Upaya Pendahuluan Pemanfaatan Gliserol dari Produk Samping Produksi Biodiesel Untuk Pembuatan Obat Batuk Gliseril Guaiakolat

    Ritmaleni Ritmaleni


    Full Text Available Berbagai kondisi reaksi basa dan asam termasuk penggunaan asam Lewis telah diaplikasikan pada reaksi antara gliserol dan o-metoksi fenol sebagai upaya dalam pemanfaatan gliserol dari hasil samping produksi biodiesel berbahan dasar minyak jelantah. Reaksi ini nantinya akan digunakan pada pembuatan obat batuk gliseril guaiakolat. Kondisi reaksi yang dilakukan belum menghasilkan suatu reaksi yang berjalan secara optimal sehingga masih diperlukan penelitian berikutnya.   Some reaction conditions in basic and acid including Lewis acid have been applied on the reaction between glycerol and o-methoxy phenol. This study is an attempt to use glycerol as by-product of waste cooking oil-based biodiesel production. This reaction will be applied for synthesizing of cough medicine named glyceryl guaiacolate. Based on the results obtained, the reaction conditions applied were still not fit yet for optimum reactionand need to be found in the further study.

  8. Guaifenesin in rhinitis.

    Storms, William; Farrar, Judith R


    Mucus in the airways is a complex mixture of water, lipids, glycoproteins, sugars, and electrolytes that serves as a lubricant for the epithelium. The efficient flow of respiratory mucus is a first level of immune defense that requires an appropriate viscosity and elasticity for optimal barrier and ciliary functions. Thickening and drying of airway mucus by respiratory tract infections, allergies, and drugs can impair evacuation. Tenacious, bothersome mucus is an annoying and frequent symptom of rhinitis that is difficult to manage. Common remedies include adequate hydration through fluid intake and nasal washes. The use of mucoactive agents is controversial due to limited data and equivocal efficacy in available studies. Nonetheless, some patients benefit. This review examines the use of guaifenesin (glyceryl guaiacolate) on bothersome nasal mucus associated with rhinitis, including the available published data and clinical experience.

  9. A dramatic drop in blood pressure following prehospital GTN administration.

    Boyle, Malcolm J


    A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient's observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient's condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold-Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold-Jarisch reflex as the cause and manage the patient accordingly.

  10. Histamine-1 receptor blockade does not prevent nitroglycerin induced migraine. Support for the NO-hypothesis of migraine

    Lassen, L H; Thomsen, L L; Kruuse, C;


    It has previously been shown that in migraine sufferers infusion of glyceryl trinitrate (GTN) and histamine causes an immediate headache during the infusion and a genuine migraine attack one to several hours after the infusion. This identical time profile indicates a common mechanism of action....... To evaluate whether GTN causes headache via liberation of histamine, we studied the effect of GTN 0.5 for 20 min in seven migraine sufferers, once after pretreatment with the histamine-1 (H1)-receptor blocker mepyramine (0.5 and once without pretreatment. This mepyramine dose...... with transcranial Doppler, were also unaffected by the mepyramine pretreatment. Our results demonstrate that neither headache nor arterial dilatation due to GTN infusion is caused by histamine release. In all likelihood the common mediator of migraine induction by GTN and histamine is nitric oxide....


    L. K. Omray


    Full Text Available Present study deals with the formulation and characterization of testosterone bearing solid lipid nanoparticles for transdermal drug delivery. Solid lipid nanoparticles of testosterone were prepared by ether injection method. Solid lipid nanoparticles were prepared by testosterone, glyceryl mono stearate, brij 35, propylene glycol and double distilled water. Four different formulations i.e. F1 to F4 were prepared in different quantity of brij 35. All the solid lipid nanoparticles formulations were characterized on the basis of electron microscopy, particle size by zeta sizer, polydispersity index, encapsulation efficiency, viscosity and in vitro drug release study. Average size and polydispersity index of developed formulation F3 found to have 298 nm and 0.328 respectively, determined by zeta sizer. Encapsulation efficiency of formulation F3 was found to have 54.16%. Viscosity of formulation was also enough to handle for transdermal application. All the formulations followed zero order release profile.

  12. Design and evaluation of an oral multiparticulate system for dual delivery of amoxicillin and Lactobacillus acidophilus.

    Govender, Mershen; Choonara, Yahya E; van Vuuren, Sandy; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness


    A delayed-release dual delivery system for amoxicillin and the probiotic Lactobacillus acidophilus was developed and evaluated. Statistical optimization of a cross-linked denatured ovalbumin protective matrix was first synthesized using a Box-Behnken experimental design prior to encapsulation with glyceryl monostereate. The encapsulated ovalbumin matrix was thereafter incorporated with amoxicillin in a gastro-resistant capsule. In vitro characterization and stability analysis of the ovalbumin and encapsulated components were also performed Results: Protection of L. acidophilus probiotic against the bactericidal effects of amoxicillin within the dual formulation was determined. The dual formulation in this study proved effective and provides insight into current microbiome research to identify, classify and use functional healthy bacteria to develop novel probiotic delivery technologies.

  13. Kinetically controlled synthesis of monoglyceryl esters from chiral and prochiral acids methyl esters catalyzed by immobilized Rhizomucor miehei lipase.

    Acosta, Andreina; Filice, Marco; Fernandez-Lorente, Gloria; Palomo, Jose M; Guisan, Jose M


    Partial acylation of only one primary hydroxyl group of glycerol generates a chiral center at position 2. Rhizomucor miehei lipase (RML) catalyzes the kinetically controlled transesterification of different aromatic carboxylic acids methyl esters with glycerol. High synthetic yields of glyceryl esters (around 70-80%) were obtained even in the presence of significant concentrations of water (from 5% to 20%). After a long incubation of the reaction mixture in the presence of the biocatalyst only pure free acid was obtained. Other lipases (from Geobacillus thermocatenulatus and from Thermomyces lanuginose) also catalyzed similar kinetically controlled transesterifications although less efficiently. RML immobilized on Sepharose-Q showed a high activity and specificity, compared to the immobilization by other techniques, only producing monoglyceryl esters with all substrates. In particular, monoglyceryl-phenylmalonate product was synthesized in 82% overall yield and >99% diastereomeric excess at pH 7.0 and 37°C and 90% glycerol.

  14. An empirical model for dissolution profile and its application to floating dosage forms.

    Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul


    A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes.

  15. Three-dimensional solubility parameters and their use in characterising the permeation of drugs through the skin.

    Groning, R; Braun, F J


    The physico-chemical properties of drug substances are major determinants of their transdermal absorption. In the present study the concept of the three-dimensional solubility parameters of Hansen was applied in conjunction with the Bagley projection to describe the permeation of drugs and model substances through the skin. Drug permeation data from the literature were compared with the calculated solubility parameters of the drugs. It was demonstrated that the permeation of drugs can be estimated by their position in the Bagley diagram. There is a linear correlation between the logarithm of the skin permeation of drugs and the exchange cohesive energy for the steroids testosterone, progesterone, hydrocortisone acetate, corticosterone, cortisone, and dexamethasone. A linear correlation can be confirmed for the permeation of glyceryl trinitrate, digitoxin, oestradiol, scopolamine, atropine, diethylcarbamazine, fentanyl, and chlorpheniramine. In the case of morphine, codeine, sufentanil, meperidine and hydromorphone there is a linear relationship, too.

  16. Nitric oxide-related drug targets in headache

    Olesen, Jes


    -called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so...

  17. Sphincter of Oddi Function and Risk Factors for Dysfunction

    Afghani, Elham; Lo, Simon K.; Covington, Paul S.; Cash, Brooks D.; Pandol, Stephen J.


    The sphincter of Oddi (SO) is a smooth muscle valve regulating the flow of biliary and pancreatic secretions into the duodenum, initially described in 1887 by the Italian anatomist, Ruggero Oddi. SO dysfunction (SOD) is a broad term referring to numerous biliary, pancreatic, and hepatic disorders resulting from spasms, strictures, and relaxation of this valve at inappropriate times. This review brings attention to various factors that may increase the risk of SOD, including but not limited to: cholecystectomy, opiates, and alcohol. Lack of proper recognition and treatment of SOD may be associated with clinical events, including pancreatitis and biliary symptoms with hepatic enzyme elevation. Pharmacologic and non-pharmacologic approaches are discussed to help recognize, prevent, and treat SOD. Future studies are needed to assess the treatment benefit of agents such as calcium-channel blockers, glyceryl trinitrate, or tricyclic antidepressants in patients with SOD. PMID:28194398

  18. Management of Raynaud's phenomenon and digital ischemia.

    Herrick, Ariane L


    This review focuses on new findings and developments relevant to the clinician caring for patients with primary and secondary [especially systemic sclerosis (SSc)-related] Raynaud phenomenon (RP). In the last 18 months, several clinical trials and observational studies of RP and of SSc-related digital ulceration have been published, reflecting increased awareness of disease burden and increased interest by pharmaceutical companies: new insights into pathophysiology are driving new approaches to treatment. Key developments are the increased use of phosphodiesterase type V inhibitors in severe RP, and of bosentan (an endothelin-1 receptor antagonist) for prevention of recurrent SSc-related digital ulcers. Other treatments being researched include topical glyceryl trinitrate (applied locally to the digits), botulinum toxin (for severe digital ischemia/ulceration), and several other drugs including oral prostanoids. Increased availability and interest in nailfold capillaroscopy, by facilitating early diagnosis of SSc, should pave the way for studies of early intervention and vascular protection.

  19. Permanent-wave dermatitis: contact allergy to cysteamine hydrochloride.

    Landers, Maeran C; Law, Sandra; Storrs, Frances J


    Cysteamine hydrochloride (CHC) is a newly recognized sensitizer found in permanent-wave solutions. We report the case of a hairdresser who was found to be allergic to CHC. Our allergic patient was patch-tested to various chemicals found in permanent-wave solutions, including CHC (1.0% in petrolatum). Patch-test reactions were positive to CHC, glyceryl thioglycolate, diglyceryl thioglycolate, p-phenylenediamine (PPD), and PPD through a piece of latex glove. Sixty-four controls to CHC (1.0% in petrolatum) had negative results. Household-weight latex gloves were protective against CHC allergy. Persons with CHC-waved hair were not allergic. CHC contained in "neutral" permanent-wave preparations has been used in American beauty salons since 1993. We briefly discuss the introduction and significance of CHC in permanent waves.

  20. Assessment of Gasoline Additive Containing Ditert-butoxypropanol

    West, Brian H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Connatser, Raynella M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lewis, Samuel Arthur [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)


    The Fuels, Engines, and Emissions Research Center completed analysis and testing of the CPS Powershot gasoline additive under the auspices of the Department of Energy’s Technical Assistance for US Small Businesses in Vehicle Technologies. Gas chromatography-mass spectrometry (GC-MS) was used to quantify the makeup of the additive, finding a predominance of 2,3-Ditert-Butoxypropanol, also known as Glyceryl Di-Tert-Butyl Ether (GTBE). Blends of the additive at 2 and 4 volume percent were subjected to a number of standard ASTM tests, including Research Octane Number, Motor Octane Number, distillation, and vapor pressure. Results show a high boiling range and low vapor pressure for the additive, and a very modest octane boosting effect in gasoline with and without ethanol.

  1. Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery.

    Wavikar, Preeti R; Vavia, Pradeep R


    In the current research work, rivastigmine (RV)-loaded in situ gelling nanostructured lipid carriers (NLCs) were developed for nose to brain delivery. NLCs were fabricated by ethanol injection method using glyceryl monosterate, Capmul MCM C8, Lecithin and Tween 80. NLCs showed average particle size of 123.2 ± 2.3 nm with entrapment efficiency of 68.34 ± 3.4%. DSC, XRD and IR studies showed complete amorphization and incorporation of the drug into nanoparticles. NLCs were incorporated into an in situ gelling system using 0.8% gellan gum and 15% Lutrol F 127. RV in situ gel showed excellent elasticity, rheology, mucoadhesion and adhesiveness to facilitate its adhesion to the upper nasal mucosa. NLC-based in situ gel showed a 2-fold increase in nasal permeation of the drug over plain RV solution. In situ gelling NLCs showed a 3-fold increase in enzyme inhibition efficacy.

  2. [Occupational contact dermatitis in hairdressers].

    Kieć-Swierczyńska, Marta; Krycisz, Beata; Chomiczewska, Dorota


    Numerous data from the medical literature show that working as a hairdresser is associated with the highest risk of occupational contact dermatitis. In Europe, hairdressers rank first of all occupation groups with the highest prevalence of occupational dermatitis. It is estimated that 10-20% and even 50% of hairdressers are affected with skin disorders. Skin problems occur soon after commencing hairdressing, in the first 2 years of work, sometimes during vocational training. The most common factors contributing to skin damage include water, shampoos, detergents, conditioners, hair dyes, bleaches, permanent wave solutions and components of gloves. Water and wet work are prime skin irritants - causal factors of irritant contact dermatitis while p-phenylenediamine, glyceryl monothioglycolate, ammonium persulfate and also fragrances, preservatives, disinfectants and metals are the most important allergens, which induce allergic contact dermatitis.

  3. Composition of the silk lipids of the spider Nephila clavipes.

    Schulz, S


    A detailed analysis of the lipids of spider silk is given for the first time. Extracts of the silk from the golden orb weaver, Nephila clavipes, were studied by gas chromatography, mass spectrometry, and chemical derivatizations. The major group of the lipids consisted of methyl-branched 1-methoxyalkanes (methyl ethers) with up to four methyl groups in the chain (chain length between C28 and C34), which are unique to spiders. The position of the methyl branches was determined by conversion into cyanides, which allowed easy location of methyl branches. The second-largest group included alkanes with a wide structural variety; 2-methyl-branched, even-numbered hydrocarbons predominated. A general numerical method for the estimation of retention indices of alkanes and their derivatives is presented. Further components of the web included alkanols and alkanediols, fatty acids, and glyceryl ethers. Some comments on the biosynthesis of these compounds are also given.

  4. Recent Advances in the Pharmacotherapy of Chronic Anal Fissure: An Update

    Bikash Medhi


    Full Text Available Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN ointment (0.2% has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fis-sures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.

  5. Renal cortical and medullary blood flow responses to altered NO availability in humans

    Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L;


    , tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4......-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P

  6. Relaxant mechanisms of 3, 5, 7, 30, 40-pentamethoxyflavone on isolated human cavernosum

    Jansakul, Chaweewan; Tachanaparuksa, Kuldej; Mulvany, Michael J.


    We have investigated effects and mechanisms responsible for the activity of 3, 5, 7, 30, 40-pentamethoxyflavone (PMF) on isolated human cavernosum. PMF is the major flavone isolated from Kaempferia parviflora claimed to act as an aphrodisiac. PMF caused relaxation of phenylephrine precontracted...... did not significantly inhibit the relaxant activity of glyceryltrinitrate or acetylcholine on human cavernosal strips precontracted with phenylephrine. In contrast, sildenafil (phosphodiesterase inhibitor) potentiated the relaxant activity of glyceryl trinitrate but not of acetylcholine. In normal...... of nitric oxide, and had no effect as a KATP- or KCa channel opener, a phosphodiesterase inhibitor, a store-operated Ca2þ channel blocker or a Rho-kinase inhibitor. Therefore, these studies suggest that PMF causes relaxation of human cavernosum through voltagedependent Ca2þ channels and other mechanisms...

  7. Formulation Development, Process Optimization, and In Vitro Characterization of Spray-Dried Lansoprazole Enteric Microparticles.

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


    This research focuses on the development of enteric microparticles of lansoprazole in a single step by employing the spray drying technique and studies the effects of variegated formulation/process variables on entrapment efficiency and in vitro gastric resistance. Preliminary trials were undertaken to optimize the type of Eudragit and its various levels. Further trials included the incorporation of plasticizer triethyl citrate and combinations of other polymers with Eudragit S 100. Finally, various process parameters were varied to investigate their effects on microparticle properties. The results revealed Eudragit S 100 as the paramount polymer giving the highest gastric resistance in comparison to Eudragit L 100-55 and L 100 due to its higher pH threshold and its polymeric backbone. Incorporation of plasticizer not only influenced entrapment efficiency, but diminished gastric resistance severely. On the contrary, polymeric combinations reduced entrapment efficiency for both sodium alginate and glyceryl behenate, but significantly influenced gastric resistance for only sodium alginate and not for glyceryl behenate. The optimized process parameters were comprised of an inlet temperature of 150°C, atomizing air pressure of 2 kg/cm(2), feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules.

  8. Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.

    Uhumwangho, M U; Okor, R S


    Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to wax proved most promising in the melt granulation of the test drug for sustained release applications.

  9. Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil

    Hetal P Thakkar


    Full Text Available This study deals with development and optimization of nanostructured lipid carriers (NLCs of candesartan cilexetil (CC for improving its oral bioavailability. From solubility and lipid-water partition studies of CC in various lipids, glyceryl monostearate (GMS and glyceryl monocaprylate were selected as solid lipid and liquid lipid, respectively. NLCs were formulated by hot melt-emulsification-ultrasonication method. A three-factor, three-level Box-Behnken design was used to optimize the independent variables, lipid: drug ratio (X1, solid lipid: liquid lipid ratio (X2 and surfactant concentration (X3. Different batches were prepared and evaluated for responses, particle size (Y1, zeta potential (Y2 and % entrapment efficiency (Y3. Response surface plots and perturbation plots were constructed to study the effect of factors on responses. The optimized formulation containing X1 - 22.47:1, X2 - 7.23:1 and X3 - 1.97% was prepared and evaluated. Observed values for Y1, Y2, and Y3 were found to be closer to the predicted values thus validating the optimization method. Differential scanning calorimetry thermograms of pure drug, GMS and lyophilized drug loaded NLCs indicated complete miscibility of drug into lipids. The release of CC from the NLCs conducted in artificial gastric fluid (pH 1.2 was much higher than in phosphate buffer solution (pH 6.8. The formulated NLCs were found to be more stable at refrigerated condition (5°C ± 3°C as compared with room temperature (25°C ± 2°C/60% RH% ± 5% RH. The use of design approach helped to identify critical formulation parameters in CC loaded NLCs preparation.

  10. Quantitative microleakage of some dentinal bonding restorative systems.

    Hasegawa, T; Retief, D H


    The quantitative microleakage of class V cementum (dentin) cavities restored with six dentinal bonding restorative systems was determined in vitro. Ninety extracted human permanent first and second mandibular and maxillary premolars were used in this study. Class V preparations were made in cementum (dentin) at the root facial surfaces. The preparations were restored with 1) a dentin bonding system containing 2% HEMA and BisGMA and a light-cured microfilled composite; 2) the same materials only substituting META/MMA base and TBB catalyst monomers for the BisGMA sealer; 3) a dentin bonding system containing 35% HEMA with META/MMA base and TBB catalyst, and a light-cured hybrid composite; 5) the same dentin bonding system only substituting the 35% glycerylmethacrylate for the 35% HEMA and using the microfilled composite; and 6) the previously described system with a substitution of 0.5 mol EDTA for the 10% citric acid -3% FeCl3. Fifteen teeth were restored with each procedure. The restorations were finished with 12-bladed carbide burs 15 min after placement, the teeth were stored in saline at 37 degrees C for 24 h, finished with Sof-Lex discs and then thermocycled in 2% methylene blue solution 500 times between 50 degrees C and 8 degrees C with a dwell time of 15 s. Quantitative microleakage was determined by a spectrophotometric dye-recovery method and expressed in microgram/dye/restoration. The data were analyzed by ANOVA, Student-Newman-Keuls and Kruskal-Wallis tests. The quantitative microleakage of the teeth restored with the adhesive systems containing 35% glyceryl methacrylate was significantly reduced. The bonding mechanism of glyceryl methacrylate is not known.

  11. Enhancing mechanism of intestinal absorption of highly lipophilic compounds using microemulsion – Quantitative analysis of the partitioning to the mesenteric lymph in intestinal cells

    Kazunori Iwanaga


    Full Text Available The purpose of this study was to quantify the effect of the fatty acid alkyl-chain length of a polyethylene glycol (PEG glyceryl ester, which was used as a microemulsion oil component, on the partitioning of highly lipophilic compounds to the mesenteric lymph after oral administration. Oil blue N, a highly lipophilic anthraquinone derivative, was orally administered to lymph duct-cannulated and untreated rats in two kinds of different microemulsions. Gelucire® 50/13 and Gelucire® 44/14 were used as the oil component with long chain and medium chain fatty acid portions, respectively, of PEG glyceryl esters in microemulsions. The cumulative amount of oil blue N in lymph fluid was almost the same between the two microemulsions, although the transferred amount of oil component (triglyceride in the lymph after administration of the Gelucire® 50/13 microemulsion was significantly higher than that of the Gelucire® 44/14 microemulsion. On the other hand, the solubility of oil blue N in Gelucire® 44/14 was much higher than that in Gelucire® 50/13. No significant differences were observed between microemulsions in the bioavailability of oil blue N. From these data, the partitioning of oil blue N to the lymph was calculated using a mathematical model, showing that the partitioning ratios of oil blue N to the lymph fluid were almost the same for both microemulsions. The solubility of oil blue N to the oil component of the microemulsions and the transfer of triglycerides to the lymph after administration of the microemulsions counteract each other, leading to similar partitioning ratios of oil blue N to the lymph.

  12. Novel Bacterial Lipoprotein Structures Conserved in Low-GC Content Gram-positive Bacteria Are Recognized by Toll-like Receptor 2*

    Kurokawa, Kenji; Ryu, Kyoung-Hwa; Ichikawa, Rie; Masuda, Akiko; Kim, Min-Su; Lee, Hanna; Chae, Jun-Ho; Shimizu, Takashi; Saitoh, Tatsuya; Kuwano, Koichi; Akira, Shizuo; Dohmae, Naoshi; Nakayama, Hiroshi; Lee, Bok Luel


    Bacterial lipoproteins/lipopeptides inducing host innate immune responses are sensed by mammalian Toll-like receptor 2 (TLR2). These bacterial lipoproteins are structurally divided into two groups, diacylated or triacylated lipoproteins, by the absence or presence of an amide-linked fatty acid. The presence of diacylated lipoproteins has been predicted in low-GC content Gram-positive bacteria and mycoplasmas based on the absence of one modification enzyme in their genomes; however, we recently determined triacylated structures in low-GC Gram-positive Staphylococcus aureus, raising questions about the actual lipoprotein structure in other low-GC content Gram-positive bacteria. Here, through intensive MS analyses, we identified a novel and unique bacterial lipoprotein structure containing an N-acyl-S-monoacyl-glyceryl-cysteine (named the lyso structure) from low-GC Gram-positive Enterococcus faecalis, Bacillus cereus, Streptococcus sanguinis, and Lactobacillus bulgaricus. Two of the purified native lyso-form lipoproteins induced proinflammatory cytokine production from mice macrophages in a TLR2-dependent and TLR1-independent manner but with a different dependence on TLR6. Additionally, two other new lipoprotein structures were identified. One is the “N-acetyl” lipoprotein structure containing N-acetyl-S-diacyl-glyceryl-cysteine, which was found in five Gram-positive bacteria, including Bacillus subtilis. The N-acetyl lipoproteins induced the proinflammatory cytokines through the TLR2/6 heterodimer. The other was identified in a mycoplasma strain and is an unusual diacyl lipoprotein structure containing two amino acids before the lipid-modified cysteine residue. Taken together, our results suggest the existence of novel TLR2-stimulating lyso and N-acetyl forms of lipoproteins that are conserved in low-GC content Gram-positive bacteria and provide clear evidence for the presence of yet to be identified key enzymes involved in the bacterial lipoprotein biosynthesis

  13. New alternatives to cosmetics preservation.

    Papageorgiou, S; Varvaresou, A; Tsirivas, E; Demetzos, C


    In recent years, there is a considerable interest in the development of preservative-free or self-preserving cosmetics. The aim of our work was to develop new cosmetic formulations by replacing chemical preservatives with ingredients with antimicrobial properties that are not legislated as preservatives according to Annex VI of Commission Directive 76/768/EEC. This paper describes the preservative efficacy of the well-known antimicrobial extracts of Lonicera caprifoleum and Lonicera japonica in combination with glyceryl caprylate and/or levulinic acid, p-anisic acid, and ethanol. We prepared a series of acidic (pH = 5.5) aqueous and O/W formulations, i.e., tonic lotion, shampoo, shower gel, conditioning cream, anticellulite cream, cleansing milk and peeling cream, containing (0.2% w/w) Lonicera extracts, alone in the case of tonic lotion and in combination with (1% w/w) glyceryl caprylate in the other products, and we performed challenge tests according to the European Pharmacopoeia procedures and criteria. Formulations such as shampoo, shower gel, and conditioning cream fulfilled criterion A, while tonic lotion, anticellulite cream, cleansing milk, and peeling cream fulfilled criterion B, in regard to contamination from A. niger. Furthermore, we evaluated the efficacy of the antimicrobial systems in two states of use: the intact product and after three weeks of consumer use. The results showed that A. niger was also detected during use by consumers in the products that satisfied only criterion B in challenge tests. The addition of antimicrobial fragrance ingredients such (safe during use. The small quantity (5% w/w) of ethanol gave an important assistance in order to boost the self-preserving system and to produce stable and safe products.

  14. Comparison of metoprolol tartrate multiple-unit lipid matrix systems produced by different technologies.

    Aleksovski, Aleksandar; Van Bockstal, Pieter-Jan; Roškar, Robert; Sovány, Tamás; Regdon, Géza; De Beer, Thomas; Vervaet, Chris; Dreu, Rok


    The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices. Prilling tended to be susceptible to increased melt viscosity. Direct compression was not applicable for mini-matrix production due to poor powder flow. In general MPT release from all matrices was affected by its loading and the size of the units/particles. Processing of GB-MPT mixtures by different techniques did not lead to different drug release rates and patterns, while in case of GPS differently obtained matrices provided diverse MPT release outcomes. Matrices based on GB tended to have higher porosity compared to ones composed of GPS and thus most of the GB-based formulations showed faster drug delivery. FT-IR analysis revealed no interactions between primary components used for matrix production and Raman mapping outlined uniform MPT distribution throughout the units. DSC and X-ray studies revealed significant changes in the crystallinity of glycerides after storage under room conditions (GPS samples) and at increased temperature (GB and GPS samples), which was correlated to the changes seen in drug release rate and pattern after storage. Media composition in general tended to insignificantly affect GB matrices, while in case of GPS matrices increasing the pH and presence of biorelevant compounds induced faster drug release.

  15. Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

    Yang Z


    Full Text Available Zhiwen Yang,1,3 Meiwan Chen,2 Muhua Yang,1 Jian Chen,1 Weijun Fang,1 Ping Xu11Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 3Shanghai Songjiang Hospital Affiliated Nanjing Medical University, Nanjing, People's Republic of ChinaAbstract: The oral administration of amphotericin B (AmB has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2 was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone®, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.Keywords: glyceryl monoolein cubosomes, oral delivery, amphotericin B, antifungal activity, absorption mechanism

  16. Emulsifier development for high-concentrated reverse emulsions

    I.L. Kovalenko


    Full Text Available The reverse emulsions have found broad application in ore mining industry as matrixes of emulsion explosive substances and boring washing waters. The defining characteristic of reverse emulsions of industrial explosive substances is the high stability and immunity to crystallization. Aim: The aim of this work is to assess the mechanism of emulsifiers effect like SMO and some PIBSA-derivatives, that are most abundantly used in world practice, and also to develop an effective domestic emulsifier of reverse emulsions. Materials and methods: Using the semi-dynamic method with use of the reverse stalagmometer it was determined the decreasing in interfacial tension on “water / diesel fuel” border in the presence of 0.5 wt % sorbitan monooleate of various producers. Emulsions with use of the chosen emulsifiers using the dynamic mixer on the basis of monosolution of ammonium nitrate and diesel fuel have been produced. The emulsions have the following composition, wt %: ammonium nitrate – 76.8; water – 15.6; diesel fuel – 6.0; emulsifier – 1.6. Results: By the researches results of the interfacial tension “surfactant water / solution in diesel fuel”, the stability of emulsions using monosolution of ammonium nitrate and the IR spectrums of SMO of various producers it is established that presence in product of impurity of oleic acid, di- and trioleates leads to decreasing in interphase activity, increasing of emulsifier oil solubility and decreasing the resistance of emulsions to crystallization. On the basis of the spectral data analysis it is suggested about possibility of specific interaction on the mechanism of “spectral resonance” between emulsifiers of the PIBSA-MEA, LZX type and crystals nucleus of NH4NO3 ammonium nitrate in dispersed phase of emulsion. Amidation of vegetable oils by monoethanol amine is implemented at the reduced temperatures (90…100 °C. It was proved the availability mainly of fatty acids amides in product

  17. Characterization of an extracellular lipase and its chaperone from Ralstonia eutropha H16.

    Lu, Jingnan; Brigham, Christopher J; Rha, Chokyun; Sinskey, Anthony J


    Lipase enzymes catalyze the reversible hydrolysis of triacylglycerol to fatty acids and glycerol at the lipid-water interface. The metabolically versatile Ralstonia eutropha strain H16 is capable of utilizing various molecules containing long carbon chains such as plant oil, organic acids, or Tween as its sole carbon source for growth. Global gene expression analysis revealed an upregulation of two putative lipase genes during growth on trioleate. Through analysis of growth and activity using strains with gene deletions and complementations, the extracellular lipase (encoded by the lipA gene, locus tag H16_A1322) and lipase-specific chaperone (encoded by the lipB gene, locus tag H16_A1323) produced by R. eutropha H16 was identified. Increase in gene dosage of lipA not only resulted in an increase of the extracellular lipase activity, but also reduced the lag phase during growth on palm oil. LipA is a non-specific lipase that can completely hydrolyze triacylglycerol into its corresponding free fatty acids and glycerol. Although LipA is active over a temperature range from 10 °C to 70 °C, it exhibited optimal activity at 50 °C. While R. eutropha H16 prefers a growth pH of 6.8, its extracellular lipase LipA is most active between pH 7 and 8. Cofactors are not required for lipase activity; however, EDTA and EGTA inhibited LipA activity by 83 %. Metal ions Mg(2+), Ca(2+), and Mn(2+) were found to stimulate LipA activity and relieve chelator inhibition. Certain detergents are found to improve solubility of the lipid substrate or increase lipase-lipid aggregation, as a result SDS and Triton X-100 were able to increase lipase activity by 20 % to 500 %. R. eutropha extracellular LipA activity can be hyper-increased, making the overexpression strain a potential candidate for commercial lipase production or in fermentations using plant oils as the sole carbon source.

  18. Actinoplanes teichomyceticus ATCC 31121 as a cell factory for producing teicoplanin


    Background Teicoplanin is a glycopeptide antibiotic used clinically in Europe and in Japan for the treatment of multi-resistant Gram-positive infections. It is produced by fermenting Actinoplanes teichomyceticus. The pharmaceutically active principle is teicoplanin A2, a complex of compounds designated T-A2-1-A2-5 differing in the length and branching of the fatty acid moiety linked to the glucosamine residue on the heptapeptide scaffold. According to European and Japanese Pharmacopoeia, components of the drug must be reproduced in fixed amounts to be authorized for clinical use. Results We report our studies on optimizing the fermentation process to produce teicoplanin A2 in A. teichomyceticus ATCC 31121. Robustness of the process was assessed on scales from a miniaturized deep-well microtiter system to flasks and 3-L bioreactor fermenters. The production of individual factors T-A2-1-A2-5 was modulated by adding suitable precursors to the cultivation medium. Specific production of T-A2-1, characterized by a linear C10:1 acyl moiety, is enhanced by adding methyl linoleate, trilinoleate, and crude oils such as corn and cottonseed oils. Accumulation of T-A2-3, characterized by a linear C10:0 acyl chain, is stimulated by adding methyl oleate, trioleate, and oils such as olive and lard oils. Percentages of T-A2-2, T-A2-4, and, T-A2-5 bearing the iso-C10:0, anteiso-C11:0, and iso-C11:0 acyl moieties, respectively, are significantly increased by adding precursor amino acids L-valine, L-isoleucine, and L-leucine. Along with the stimulatory effect on specific complex components, fatty acid esters, oils, and amino acids (with the exception of L-valine) inhibit total antibiotic productivity overall. By adding industrial oils to medium containing L-valine the total production is comparable, giving unusual complex compositions. Conclusions Since the cost and the quality of teicoplanin production depend mainly on the fermentation process, we developed a robust and scalable

  19. Actinoplanes teichomyceticus ATCC 31121 as a cell factory for producing teicoplanin

    Taurino Carlo


    Full Text Available Abstract Background Teicoplanin is a glycopeptide antibiotic used clinically in Europe and in Japan for the treatment of multi-resistant Gram-positive infections. It is produced by fermenting Actinoplanes teichomyceticus. The pharmaceutically active principle is teicoplanin A2, a complex of compounds designated T-A2-1-A2-5 differing in the length and branching of the fatty acid moiety linked to the glucosamine residue on the heptapeptide scaffold. According to European and Japanese Pharmacopoeia, components of the drug must be reproduced in fixed amounts to be authorized for clinical use. Results We report our studies on optimizing the fermentation process to produce teicoplanin A2 in A. teichomyceticus ATCC 31121. Robustness of the process was assessed on scales from a miniaturized deep-well microtiter system to flasks and 3-L bioreactor fermenters. The production of individual factors T-A2-1-A2-5 was modulated by adding suitable precursors to the cultivation medium. Specific production of T-A2-1, characterized by a linear C10:1 acyl moiety, is enhanced by adding methyl linoleate, trilinoleate, and crude oils such as corn and cottonseed oils. Accumulation of T-A2-3, characterized by a linear C10:0 acyl chain, is stimulated by adding methyl oleate, trioleate, and oils such as olive and lard oils. Percentages of T-A2-2, T-A2-4, and, T-A2-5 bearing the iso-C10:0, anteiso-C11:0, and iso-C11:0 acyl moieties, respectively, are significantly increased by adding precursor amino acids L-valine, L-isoleucine, and L-leucine. Along with the stimulatory effect on specific complex components, fatty acid esters, oils, and amino acids (with the exception of L-valine inhibit total antibiotic productivity overall. By adding industrial oils to medium containing L-valine the total production is comparable, giving unusual complex compositions. Conclusions Since the cost and the quality of teicoplanin production depend mainly on the fermentation process, we

  20. 豆腐渣在面包中的应用研究%Application of bean curd residue in bread

    芦菲; 李波; 张翼; 张直


    Bean curd residue is the by-product of tofu and soybean milk manufactures.It contains rich dietary fiber and protein,and can improve the nutritional value when adding it into bread.Analyzed the effects of bean curd residue,gluten,ascorbic acid sodium,glucose oxidase,α-amylase,glyceryl monostearate,and xanthan gum on bread quality.The results showed that the optimal replacement of bean curd residue powder for flour was 10%.Adding 8% of gluten can markedly improve the bread qulity.Adding 1~5mg/100g of glucose oxidase,0.6mg/100g of α-amylase,0.6% of glyceryl monostearate,or 0.4% of xanthan gum could increase the bread quality to some extent.The best ingredient of bean curd residue bread was 90g of bread flour,10g of bean curd residue powder,8g of gluten,1.5g of yeast,1.0g of salt,10g of sugar,and 0.6g of glyceryl monostearate.%豆腐渣是加工豆腐、豆浆等产品的副产物,富含膳食纤维、蛋白质等营养成分,将其添加到面包中能够改善面包的营养价值。研究了豆腐渣粉、谷朊粉、异抗坏血酸钠、葡萄糖氧化酶、α-淀粉酶、单硬脂酸甘油酯、黄原胶添加量对面包品质的影响,结果显示,豆腐渣粉替代面粉的量以10%为宜,添加8%的谷朊粉能够显著改善豆渣面包的品质,添加1~5mg/100g的葡萄糖氧化酶、0.6mg/100g的α-淀粉酶、0.6%的单硬脂酸甘油酯或0.4%的黄原胶对豆渣面包品质有一定的改良作用。豆腐渣面包的最佳配方为:面包粉90g、豆腐渣粉10g、谷朊粉8g、酵母1.5g、食盐1.0g、砂糖10g、单硬脂酸甘油酯0.6g。

  1. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor


    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol(®)), Glyceryl palmitostearate (Precirol(®)), Glyceryl behenate (Compritol(®)) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol(®) (eR = 0.891-0.997), Precirol(®) (eR = 0.611-0.743), Compritol(®) (eR = 0.665-0.729) and Carnauba wax (eR = 0.499-0.551). Highly spherical pellets were obtained with Geleol(®) (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol(®) and Compritol(®), (ii) Geleol(®) and Carnauba wax and (iii) Geleol(®), Compritol(®) and Carnauba wax. Scanning electron microscopy of Compritol(®) pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol(®) and Compritol(®) pellets, explained by Korsmeyer-Peppas (R(2) = 0.978-0.993) indicated

  2. 中心组合设计-效应面法优化曲安奈德固体脂质纳米粒处方%Optimization of Triamcinolone Acetonide-loaded Solid Lipid Nanoparticles Formula by Central Composite Design and Response Surface Methodology

    邱凯锋; 黄嗣航; 蔡宝玲; 廖龙荣; 梁启发


    OBJECTIVE To optimize the formula of triamcinolone acetonide-loaded solid lipid nanoparticles(TACA-SLN). METHODS Central composite design and response surface methodology was applied to screen TACA-SLN prescription. The influence factors such as F68 concentration, the ratio of glyceryl monostearate to lecithin, the ratio of drug to lipids, the ratio of water phase to organic phase were investigated using entrapment efficiency as evaluation parameter. TACA-SLN was prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature. RESULTS The optimum prescription was: F68 1.89%, the ratio of glyceryl monostearate to lecithin was 1.95, the ratio of drug to lipids was 0.15, the ratio of water phase to organic phase was 5.68. The bias was 0.07%. CONCLUSION Cental composite design and response surface metogology was successfully used to optimize the formulation of TACA-SLN.%目的 采用中心组合设计-效应面法优化曲安奈德固体脂质纳米粒(TACA-SLN)的处方.方法 采用中心组合设计-效应面优化法筛选处方,以曲安奈德包封率作为评价指标,考察泊洛沙姆188的浓度,单硬脂酸甘油酯和大豆卵磷脂的质量比,药物和脂质材料的质量比,水相和有机相的体积比对评价指标的影响.采用高温乳化-低温固化法制备TACA-SLN.结果 优选的最佳处方为:泊洛沙姆188浓度1.89%,单硬脂酸甘油酯与大豆卵磷脂质量比1.95,药物与脂质质量比0.15,水相与油相体积比5.68,实验值与理论值偏差0.07%.结论 中心组合设计-效应面法能有效优选TACA-SLN处方.

  3. 一类阴离子型高分子沥青乳化剂的合成及乳化沥青的性能%Synthesis of a Kind Anionic Polymer Emulsifier and the Performance of Their Emulsified Asphalt

    张宝砚; 席曼; 梁博; 王琦; 王建华


    Glycerol for matrix surface active monomer polymerization was used to synthesize two new anionic polymer asphalt emulsifier, poly (2-glyceryl undecylenate) dicarboxylate and poly (2-glyceryl oleate) dicarboxylate. Using infrared spectroscopy (IR), near-infrared (NIR) analysis and I H nuclear magnetic resonance (1H-NMR), the structures of sample were identified. -Mn were got from gel permeation chromatography (GPC). The stability of the hard water, mixing stability and other tests were conducted respectively. And the mechanism of emulsification was studied. The results show that: the synthetic material is target product, which has good hard water stability. And both of them are slow crack asphalt emulsifier. The hydrogen bonds are formed between ester in molecular and hydroxyl in asphaltene, as well as the oxygen in carboxyl ions and water molecules, resulting stabilize asphalt emulsion.%以丙三醇与十一烯酸和油酸为原料,制备了聚(2-十一烯甘油酯)二羧酸钠和聚(2-油酸甘油酯)二羧酸钠两种阴离子型高分子沥青乳化剂。采用红外光谱、近红外和核磁对样品结构予以鉴定,通过凝胶渗透色谱仪对其-Mn进行测定,分别进行硬水稳定性、拌合稳定度和其他国家标准的测试,并对它们的乳化机理进行分析。结果表明,合成物质为目标产物;-Mn分别为3200 g/mol和4100 g/mol;硬水稳定性分别为4级和3级;二者均为慢裂型沥青乳化剂;由于分子结构中亲水基含有大量氧原子,在乳化沥青中与水分子形成大量氢键使乳化沥青稳定。

  4. Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

    Shen, Jinyang; Bi, Jianping; Tian, Hongli; Jin, Ye; Wang, Yuan; Yang, Xiaolin; Yang, Zhonglin; Kou, Junping; Li, Fei


    Background Akebia saponin D (ASD) exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD. Methods ASD–phospholipid complex (APC) was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats. Results The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n-octanol. Peceol (Glyceryl monooleate [type 40]), Cremophor® EL (Polyoxyl 35 castor oil), and Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil, surfactant, and cosurfactant, respectively. The optimal formulation was composed of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size of 148.0±2.7 nm and a zeta potential of −13.7±0.92 mV after dilution with distilled water at a ratio of 1:100 (w/w) and good colloidal stability. Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater Cmax1 (733.4±203.8 ng/mL) than ASD (437.2±174.2 ng/mL), and a greater Cmax2 (985.8±366.6 ng/mL) than ASD (180.5±75.1 ng/mL) and APC (549.7±113

  5. 植物绝缘油主要组分的理化与电气性能研究%Physical-chemical and Electrical Properties Study of Main Components in Vegetable Insulating Oils

    陈朋; 余辉; 陈江波; 蔡胜伟; 周翠娟; 于萍; 罗运柏


    A glyceryl linoleate was separated and purified by ester exchange reaction and urea adduct method from commercial sunflower seed oil. The glyceryl linoleate was used as the standard substance of main components of vegetable oils, and the physical-chemical and electrical properties of three main components of vegetable oils were tested, and the effects of unsaturated degree of the oils on their physi-cal-chemical properties, electrical properties and oxidation stability were studied. The results show that the higher the saturation degree of the oils, the higher the flash point is. The higher the unsaturated de-gree of the oils, the lower the pour point and kinematic viscosity are. The lower the unsaturated degree of the oils, the better the oxidation stability is. The relative dielectric constant of the vegetable oils is higher than that of the mineral transformer oil.%以市售葵花籽油为原料,通过酯交换反应、尿素包合法等工艺分离提纯出亚油酸甘油酯,用作植物油中主要组分的标准物质,检测了菜籽油中含量较高的3种主要化学成分的理化与电气性能,研究了油脂不饱和度对其理化性能、电气性能和氧化安定性的影响。结果表明:油脂的饱和度越高,闪点越高;油脂的不饱和度越高,倾点越低,运动粘度越低;油脂的不饱和度越低,氧化安定性越好;植物油脂的相对介电常数高于矿物变压器油的相对介电常数。

  6. Multi-proxy geochemical analyses of Indus Submarine Fan sediments sampled by IODP Expedition 355: implications for sediment provenance and palaeoclimate reconstructions

    Bratenkov, Sophia; George, Simon C.; Bendle, James; Liddy, Hannah; Clift, Peter D.; Pandey, Dhananjai K.; Kulhanek, Denise K.; Andò, Sergio; Tiwari, Manish; Khim, Boo-Keun; Griffith, Elizabeth; Steinke, Stephan; Suzuki, Kenta; Lee, Jongmin; Newton, Kate; Tripathi, Shubham; Expedition 355 Scientific Party


    petrography and heavy mineral analysis, geochemical data, isotope composition, and biomarker analysis. Preliminary organic geochemistry data suggest an increase of terrigenous organic matter input into sediment starting around 10.5 Ma, with a strong decrease in the last 1 Ma. Moreover, the detailed analyses of the glyceryl dialkyl glyceryl tetraether (GDGT) and alkenone lipids provide the first sea surface temperature (SST) reconstructions in the region. These data indicate decreasing SST from the Middle Miocene Climatic Optimum until today. This research provides an exceptional opportunity to apply a multiproxy approach to understand sediment provenance, erosional processes, and palaeoclimate evolution in the eastern Arabian Sea.

  7. A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP pancreatitis and on the successful rate of cannulation of bile ducts

    Wang Chun-hui


    Full Text Available Abstract Background Glyceryl trinitrate (GTN has been shown to be able to relax the sphincter of Oddi (SO both in animals and humans. Theoretically, the use of these compounds during and after endoscopic retrograde cholangiopancreatgraphy (ERCP could relax the biliary and pancreatic sphincters, facilitating cannulation of common bile duct (CBD during the procedure, or minimizing potential pancreatic outflow obstruction after the procedure. However, clinical trials evaluating the protective effect of GTN on the post-endoscopic retrograde cholangiopancreatgraphy pancreatitis (PEP have yielded inconclusive results. This meta-analysis is to systematically assess the effect of prophylactic administration of glyceryl trinitrate (GTN on the prevention of PEP and the effect on the cannulation of bile ducts. Methods By searching PubMed (1966 to September 2009, CENTRAL (Cochrane Controlled trials Register; issue 3, 2009 and (1984 to September 2009, two independent reviewers systematically identified prospective randomized controlled trials (RCTs detecting the effect of prophylactic GTN on the incidence of PEP and on the cannulation of bile ducts. A meta-analysis of these clinical trials was then performed. Results There are 55/899(6.1% patients suffering PEP in the treatment group versus 95/915(10.4% patients in the placebo group. The overall pooled risk of PEP was significantly lower in the GTN group than in the placebo group (OR 0.56, 95% CI: 0.40 to 0.79, p = 0.001. Subgroup analyses suggested that GTN administered by the sublingual form (OR 0.34,95% CI:0.16 to 0.75, p = 0.007 is more effective than transdermal route(OR 0.64,95% CI:0.40 to 1.01, p = 0.05, and the protective effect of GTN was far more obvious in the centers with high incidence of PEP (OR 0.40, 95% CI:0.24 to 0.67, p = 0.0006 than those centers with a low incidence of PEP (OR 0.75, 95% CI: 0.47 to 1.20, p = 0.22. Additionally, the meta-analysis suggests that GTN was not

  8. Formulation and evaluation of a water-in-oil cream containing herbal active ingredients and ferulic acid.

    Moldovan, Mirela; Lahmar, Abir; Bogdan, Cătălina; Părăuan, Simona; Tomuţă, Ioan; Crişan, Maria


    The main aims of the present study were to formulate an anti-age cream based on vegetal ingredients and ferulic acid and to evaluate the physical characteristics and the efficacy of the cream. The active ingredients were Centella asiatica oil, Spilanthes acmella oil, Zingiber officinale extract and ferulic acid. Formulation 1 (F1) was prepared using glyceryl stearate and Ceteareth-25® as emulsifiers and Formulation 2 (F2) using glyceryl stearate and potassium cetyl phosphate, all other ingredients remaining the same. The physical characterization of the creams was performed and the following parameters were analyzed: viscosity, oil droplet size, polydispersity index; also, texture analysis was performed. The anti-aging effect of the F2 was evaluated by assessing the cutaneous density before and after cream application using DUB-cutis® scanner. The mean diameter of oil drops was 10.26±4.72 mm (F1) and 22.72±7.93 mm (F2) and the polydispersity index was 35.4% and 45.7%, respectively. The mean values for consistency were 594.7±10.3 g (F1) and 300.5±14.5 g (F2), the average values for adhesion were 15.61±0.8 mJ (F1) and 22.25±4.3 mJ (F2), for firmness were 51.2±0.8 g (F1) and 30.3±4.3 g (F2) and the spreadability had values between 72.63 mm2 (F1) and 73.3 mm2 (F2). In vivo study revealed that the mean values of the cutaneous density increased from 9.21±1.39 % to 12.50±1.44 % after 8 weeks of cream application. The herbal ingredients incorporated in the O/W cream base for the antioxidant activity and anti-wrinkle effect, induced changes of the cutaneous density, an important parameter which quantifies the regeneration process of the skin. An anti-age cream containing herbal active ingredients and ferulic acid with appropriate physical characteristics was obtained. In vivo study of clinical efficacy revealed a positive effect on skin density, which increased after 8 weeks of cream application.

  9. Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging

    Mahdi ES


    Full Text Available Elrashid Saleh Mahdi1, Azmin Mohd Noor1, Mohamed Hameem Sakeena1, Ghassan Z Abdullah1, Muthanna F Abdulkarim1, Munavvar Abdul Sattar2 1Department of Pharmaceutical Technology, 2Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia Background: Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria for skin antiaging. Methods: Palm kernel oil esters (PKOEs-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH method. Results: Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween® 80/Span® 80 (9/1 with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween® 80/Span® 80 (9/1 with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane

  10. A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses.

    Lupi, Francesca R; Shakeel, Ahmad; Greco, Valeria; Oliviero Rossi, Cesare; Baldino, Noemi; Gabriele, Domenico


    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.

  11. Development and evaluation of sustained-release ibuprofen-wax microspheres. I. Effect of formulation variables on physical characteristics.

    Adeyeye, C M; Price, J C


    A congealable disperse phase encapsulation method was used to prepare sustained-release ibuprofen-wax microspheres. Microspheres prepared with paraffin wax, such as ceresine and microcrystalline waxes, using polyvinylpyrrolidone (PVP) as dispersant had a tendency to aggregate, but the addition of wax modifiers (stearyl alcohol and glyceryl monostearate) greatly reduced aggregation. Optimum modifier and dispersant concentrations were 20% (w/w) and 5% (w/v), respectively. The particle size distribution of the microspheres was log-normal. An increase in modifier, dispersant concentration, emulsification stirring speed, or temperature shifted the size distribution toward finer particles. Microcrystalline wax required a higher emulsification temperature and produced finer particles than ozokerite wax. The recovery of drug from the different microsphere formulations varied between 71 and 92%. Differential scanning calorimetry (DSC) of the single components and physical mixtures showed endothermic peaks at the respective melting-point ranges. The DSC of the ceresine and microcrystalline wax microspheres was similar to rescans of ternary mixtures of components of the microspheres with less prominent and lower melting temperatures than individual components or physical mixtures.

  12. Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.

    Adeyeye, C M; Price, J C


    A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.

  13. The effect of wax on compaction of microcrystalline cellulose beads made by extrusion and spheronization.

    Iloañusi, N O; Schwartz, J B


    The effect of wax on the deformation behavior and compression characteristics of microcrystalline cellulose (Avicel PH-101) and acetaminophen (APAP) beads is described. Beads of Avicel PH-101 and APAP formulations were prepared using extrusion and spheronization technology. A waxy material, glyceryl behenate, N.F. (Compritol), was added to the formulations in amounts ranging from 10% to 70% of total solid weight. Beads with a selected particle size range of 16-30 mesh were compressed with an instrumented single punch Manesty F press utilizing a 7/16-in. flat-faced tooling set. Compaction profiles were generated for the tablets to evaluate the effect of wax on the densification of beads containing wax. Beads made without wax (the control formulation) required greater compression forces to form cohesive tablets. As the amount of wax in the bead formulation was increased, the beads become more plastic and compressible. The Heckel equation which relates densification to compression pressure was used to evaluate the deformation mechanisms of the bead formulations. The analysis shows that as the level of wax in the bead formulation is increased, the yield pressure decreases, indicating that the beads densify by a plastic deformation mechanism.

  14. [Serum metabolomics analysis on benign prostate hyperplasia in mice based on liquid chromatography-mass spectrometry].

    Geng, Yue; Sun, Fengxia; Ma, Yu; Deng, Ligang; Lü, Jianyun; Li, Teng; Wang, Congcong


    Benign prostatic hyperplasia (BPH) increasingly becomes a common factor affecting the quality of life of aging men. Its pathogenesis has not yet been fully elucidated. Ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was employed to detect the changes of serum metabolites in normal mice, benign prostatic hyperplasia model mice and BPH model mice with finasteride intervention. The serum metabolite profiles of the three groups of mice were analyzed. Partial least squares-discriminant analysis (PLS-DA) was used for group differentiation and biomarker selection. The results showed good distinction among the three groups of mice serum metabolite spectra. Three potential biomarkers, 1-hexadecanoyl-SN-glycero-3-phosphocholine, 1-O-hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine and (Z)-13-docosenamide, were discovered and identified. They all indicated the occurrence of benign prostatic hypertrophy is closely related to the disorders of lipid metabolism. Coinpared with the control group, the contents of the first two substances were significantly increased in the serum of BPH model mice, and significantly decreased after intervened by finasteride. The contents of (Z)-13-docosenamide decreased significantly in the serum of model group, and increased after intervened by finasteride. Compared with the control group, the contents of three biomarkers in finasteride group did not recover completely and had significant differences. This study is conductive to open new avenues of diagnosis and medical treatment for BPH.

  15. Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique

    Harshal Ashok Pawar


    Full Text Available Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation.

  16. Vitamin D Deficiency Reduces the Immune Response, Phagocytosis Rate, and Intracellular Killing Rate of Microglial Cells

    Onken, Marie Luise; Schütze, Sandra; Redlich, Sandra; Götz, Alexander; Hanisch, Uwe-Karsten; Bertsch, Thomas; Ribes, Sandra; Hanenberg, Andrea; Schneider, Simon; Bollheimer, Cornelius; Sieber, Cornel; Nau, Roland


    Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections. PMID:24686054

  17. Micro and nanocomposites of polybutadienebased polyurethane liners with mineral fillers and nanoclay: thermal and mechanical properties

    Ross Pablo


    Full Text Available Micro and nanocomposites of hydroxyl terminated polybutadiene (HTPB-based polyurethanes (NPU were obtained using five mineral fillers and Cloisite 20A nanoclay, respectively. Samples were prepared by the reaction of HTPB polyol and toluene diisocyanate (TDI, and the chain was further extended with glyceryl monoricinoleate to produce the final elastomeric polyurethanes. Mechanical and thermal properties were studied, showing that mineral fillers (20%w/w significantly increased tensile strength, in particular nanoclay (at 5% w/w. When nanoclay-polymer dispersion was modified with a silane and hydantoin-bond promoter, elongation at break was significantly increased with respect to NPU with C20A. Thermal properties measured by differential scanning calorimetry (DSC were not significantly affected in any case. The molecular structure of prepared micro and nanocomposites was confirmed by Fourier transform infrared (FTIR spectroscopy and Raman spectroscopy. Interaction of fillers with polymer chains is discussed, considering the role of silanes in compatibilization of hydrophilic mineral fillers and hydrophobic polymer. The functionalization of nanoclay with HMDS silane was confirmed using FTIR. Microstructure of NPU with C20A nanoclay was confirmed by Atomic Force Microscopy (AFM.

  18. Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations.

    Green, Daniel J; Walsh, Jennifer H; Maiorana, Andrew; Best, Matthew J; Taylor, Roger R; O'Driscoll, J Gerard


    We have pooled data from a series of our exercise training studies undertaken in groups with a broad range of vascular (dys) function to the examine the hypothesis that exercise-induced improvements in the conduit and/or resistance vessel function are related to improvements in risk factors for cardiovascular (CV) disease. Endothelium-dependent and -independent conduit vessel function were assessed by using wall tracking of high-resolution ultrasound images of the brachial artery response to flow-mediated dilation (FMD) and glyceryl trinitrate. Resistance vessel function was assessed using intrabrachial administration of acetylcholine (ACh), sodium nitroprusside, and NG-monomethyl-l-arginine. Randomized cross-over studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic (n = 11), treated hypercholesterolemic (n = 11), coronary artery disease (n = 10), chronic heart failure (n = 12), Type 2 diabetic (n = 15), and healthy control subjects (n = 16). Exercise training did not significantly alter plasma lipids, blood pressure, blood glucose, waist-to-hip ratio, or body mass index values, despite significant improvement in both FMD and ACh responses. There were no correlations between changes in any risk factor variables and indexes of either resistance or conduit vessel function. We conclude that, in these subjects with antecedent vascular dysfunction, the beneficial effects of relatively short-term exercise training on vascular function are not solely mediated by the effects of exercise on CV risk factors.

  19. Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation, optimization and in vivo evaluation.

    Nooli, Mounika; Chella, Naveen; Kulhari, Hitesh; Shastri, Nalini R; Sistla, Ramakrishna


    Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery. Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug-excipients interactions, powder X-ray diffraction analysis and drug release in vitro. The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100 nm, PDI 0.291, zeta potential of -23.4 mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration. In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.

  20. Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.

    Kundu, Paromita; Das, Manasi; Tripathy, Kalpalata; Sahoo, Sanjeeb K


    Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.

  1. Towards a versatile technique for tracking nanoparticle-mucus interaction: a step on the road

    Nafee, N.; Schneider, M.


    Respiratory mucus is one of the main barriers for nanoparticle-based pulmonary delivery systems. This holds true especially for lung diseases like cystic fibrosis, where a very tenacious thick mucus layer hinders particle diffusion to the lung epithelium or the target area. Typically, mean square displacement of particles is used for mobility evaluation. In contrast, our objective is to develop a feasible technique to track directed particle penetration as a prerequisite for efficient pulmonary nanotherapy. Therefore, particle diffusion in artificial mucus was monitored based on confocal laser scanning microscopy (CLSM) and particle-mucus interaction was observed. As pharmaceutical relevant and benign materials, solid lipid nanoparticles (SLNs) were prepared by hot-melt emulsification using glyceryl behenate and different stabilizing agents such as poloxamer-407, tween-80, and polyvinyl alcohol (PVA). The diffusion of labeled SLNs in stained artificial sputum representing CF-patient sputum was verified by 3D time laps imaging. Thus, the effect of coating, particle size and mucus viscosity on nanoparticle diffusion was studied. Using image analysis software "Image J", the total fluorescent signal after 30 min in case of poloxamer-coated SLNs was 5 and 100 folds higher than tween- and PVA-coated SLNs, respectively. Nevertheless, increasing mucus viscosity reduced the diffusion of tweencoated SLNs by a factor of 10. Studying particle-mucus interaction by CLSM can be considered a promising and versatile technique.

  2. A mimicry of an acute coronary syndrome.

    Teo, Bervin


    A 79-year-old woman was out in the garden having lunch on a hot summer day. She developed stabbing chest pains, more severe on her left side, associated with radiation down her left arm. Severity was 7 out of 10. There was no relief of pain with glyceryl trinitrate spray. Risk factors for ischaemic heart disease include hyperlipidaemia, being an ex-smoker (40 years), no history of diabetes or hypertension. There was a family history of her father having a myocardial infarction at the age of 54. Echocardiogram (ECG) revealed widespread deep symmetrical T-wave inversion in the chest leads and lateral limb leads. The patient's serum creatine kinase level was 180 IU/litre (normal range 30-135), troponin I level was 6.56 g/litre (normal range 0-0.10), D-dimer was negative and random serum cholesterol level was 5.3 mmol/litre (3.8-5.2). Significant coronary stenoses were excluded. A left ventriculogram revealed a hyperkinetic base and a dyskinetic apical region of the left ventricle. Echocardiography showed normal valves, basal septal hypertrophy and a dilated akinetic apex, with the region of akinesia spanning more than the arterial territory. Takotsubo cardiomyopathy. Treatment with aspirin, angiotensin-converting enzyme (ACE) inhibitor, β blocker and a statin.

  3. One-pot synthesis of quantum dot-labeled hydrophilic molecularly imprinted polymer nanoparticles for direct optosensing of folic acid in real, undiluted biological samples.

    Yang, Yaqiong; Wang, Zhengzheng; Niu, Hui; Zhang, Huiqi


    A facile and efficient one-pot approach for the synthesis of quantum dot (QD)-labeled hydrophilic molecularly imprinted polymer (MIP) nanoparticles for direct optosensing of folic acid (FA) in the undiluted bovine and porcine serums is described. Hydrophilic macromolecular chain transfer agent-mediated reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization was used to implement the molecular imprinting of FA in the presence of CdTe quantum dots (QDs). The resulting FA-imprinted polymer nanoparticles with surface-grafted hydrophilic poly(glyceryl monomethacrylate) brushes and QDs labeling not only showed outstanding specific molecular recognition toward FA in biological samples, but also exhibited good photostability, rapid binding kinetics, and obvious template binding-induced fluorescence quenching. These characteristics make them a useful fluorescent chemosensor for directly and selectively optosensing FA in the undiluted bovine and porcine serums, with its limit of detection being 0.025μM and average recoveries ranging from 98% to 102%, even in the presence of several interfering compounds. This advanced fluorescent MIP chemosensor is highly promising for rapid quantification of FA in such applications as clinical diagnostics and food analysis.

  4. Liquid crystalline phase as a probe for crystal engineering of lactose: carrier for pulmonary drug delivery.

    Patil, Sharvil S; Mahadik, Kakasaheb R; Paradkar, Anant R


    The current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size ∼ 71 μm) lactose particles with smooth surface containing mixture of α and β-lactose was recovered from gel, however percentage of α-lactose was more as compared to β-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose® ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations.

  5. Physical-Chemical Characterization and Formulation Considerations for Solid Lipid Nanoparticles.

    Chauhan, Harsh; Mohapatra, Sarat; Munt, Daniel J; Chandratre, Shantanu; Dash, Alekha


    Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly used for the preparation of GMO-chitosan nanoparticles were characterized by modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X-ray powder diffraction techniques. GMO-chitosan nanoparticles containing poloxamer 407 as a stabilizer in the absence and presence of polymers as crystallization inhibitors were prepared by ultrasonication. The effect of polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO showed an exothermic peak at around -10°C while cooling and another exothermic peak at around -12°C while heating. It was followed by two endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are corroborated by cryo-microscopy and cryo-X-ray. Significant differences in exothermic and endothermic transition were observed between different grades of GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase in particle size after lyophilization. MDSC confirmed that nanoparticles showed similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed that PVP inhibits GMO crystallization and addition of PVP showed no significant increase in particle size of solid lipid nanoparticle (SLN) during lyophilization. The research highlights the importance of extensive physical-chemical characterization for successful formulation of SLN.

  6. Influence of Surfactant and Lipid Type on the Physicochemical Properties and Biocompatibility of Solid Lipid Nanoparticles

    Carine Dal Pizzol


    Full Text Available Nine types of solid lipid nanoparticle (SLN formulations were produced using tripalmitin (TPM, glyceryl monostearate (GM or stearic acid (SA, stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around −11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results.

  7. Influence of surfactant and lipid type on the physicochemical properties and biocompatibility of solid lipid nanoparticles.

    Pizzol, Carine Dal; Filippin-Monteiro, Fabíola Branco; Restrepo, Jelver Alexander Sierra; Pittella, Frederico; Silva, Adny Henrique; Alves de Souza, Paula; Machado de Campos, Angela; Creczynski-Pasa, Tânia Beatriz


    Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around -11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results.

  8. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    Praveen Kumar Gaur


    Full Text Available Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5±3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75±5% relative humidity (RH for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡ and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES.

  9. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael


    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

  10. Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity.

    De Marino, Simona; Gala, Fulvio; Zollo, Franco; Vitalini, Sara; Fico, Gelsomina; Visioli, Francesco; Iorizzi, Maria


    Dragon's blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-beta-O-4'- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods ((1)H-, (13)C- NMR and 2D-NMR experiments), ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex) exhibited the highest antioxidant activity.

  11. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

    Rajan Rajabalaya


    Full Text Available The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT for the treatment of overactive bladder (OAB. Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE, vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.


    S. Kiran Kumar*, T. Ramarao, D.B.R.N. Bikshapathi and K.N. Jayaveera


    Full Text Available Felodipine is a long-acting 1, 4-dihydropyridine calcium channel blocker, used to control hypertension by selective action on peripheral resistance. The conventional felodipine tablet gives a rather high peak and comparatively low trough levels, due to rapid absorption and distribution. More sustained plasma concentrations might thus produce a more even effect on blood pressure. The main aim of the study was to improve dissolution rate of the dosage form in a controlled manner over extended period of 24 hrs. Matrix tablets were prepared by direct compression method,using hydrophobic polymers like Glyceryl monostearate and Carnauba wax. The prepared formulations were evaluated for hardness, thickness, weight variation, friability and in-vitro dissolution studies. Among all the formulations F8 was selected as optimized formulation based on the evaluation parameters and in-vitro release profile of 100% drug release for 24 hrs. The FTIR and DSC results of optimized formulation showed no drug-excipient interaction. For optimized formulation(F8, the drug release mechanism was explored and explained by zero-order (r2=0.984, first-order (r2=0.947, Higuchi (r2=0.967 and Korsmayer-peppas (r2=0.982 & n=0.855 equations, which explained the drug release follows zero-order and is fit for Higuchi equation & mechanism was anomalous diffusion i.e diffusion and erosion.

  13. Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation, in vitro and in vivo evaluation.

    Shan-Bin, Guo; Yue, Tian; Ling-Yan, Jian


    Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.

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

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


    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.

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

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


    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.

  16. Effects of some lubricants and evaluation of compression parameters on directly compressible powders.

    Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa


    The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant "Hexagonal boron nitride (HBN)" on direct compression powders. Lubricants such as magnesium stearate, glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied in this article. Tablets were manufactured on an instrumented tablet press with various lubricant concentrations. Bulk and tapped densities, and Carr's index parameters were calculated for powders. Tensile strength, cohesion index, lower punch ejection force and lubricant effectiveness values were investigated for tablets. The deformation mechanisms of tablets were studied during compression from the Heckel plots with or without lubricants. Powders formulated with MGST and HBN showed better flow properties based on Carr's index. MGST was found to be the most effective lubricant based on lubricant effectiveness for tablets. HBN was found very close to MGST with the same concentrations. Other lubricants showed less effectiveness than that of MGST and HBN. It is observed that an increase in the concentration of HBN leads to decreased tensile strength and cohesion index values because of its surface-covering property. Despite covering property, HBN had no significant effect on disintegration time. Based on the Heckel plots at the level of 1%, HBN showed the most pronounced plastic character.

  17. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses.

    Jung, Hyun Jung; Abou-Jaoude, Michelle; Carbia, Blanca E; Plummer, Caryn; Chauhan, Anuj


    Glaucoma is the second major cause of blindness in the world after cataract. Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability. Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability. To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol. The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol. The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature. The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important. Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading. A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties. Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP.

  18. Patellar Tendinopathy.

    Schwartz, Aaron; Watson, Jonathan N; Hutchinson, Mark R


    Patellar tendinopathy is a common condition. There are a wide variety of treatment options available, the majority of which are nonoperative. No consensus exists on the optimal method of treatment. PubMed spanning 1962-2014. Clinical review. Level 4. The majority of cases resolve with nonoperative therapy: rest, physical therapy with eccentric exercises, cryotherapy, anti-inflammatories, corticosteroid injections, extracorporeal shockwave therapy, glyceryl trinitrate, platelet-rich plasma injections, and ultrasound-guided sclerosis. Refractory cases may require either open or arthroscopic debridement of the patellar tendon. Corticosteroid injections provide short-term pain relief but increase risk of tendon rupture. Anti-inflammatories and injectable agents have shown mixed results. Surgical treatment is effective in many refractory cases unresponsive to nonoperative modalities. Physical therapy with an eccentric exercise program is the mainstay of treatment for patellar tendinopathy. Platelet-rich plasma has demonstrated mixed results; evidence-based recommendations on its efficacy cannot be made. In the event that nonoperative treatment fails, surgical intervention has produced good to excellent outcomes in the majority of patients. © 2015 The Author(s).

  19. Pharmacological interventions for the treatment of Achilles tendinopathy: a systematic review of randomized controlled trials.

    Maffulli, Nicola; Papalia, Rocco; D'Adamio, Stefano; Diaz Balzani, Lorenzo; Denaro, Vincenzo


    Several pharmacological interventions have been proposed for the management of Achilles tendinopathy, with no agreement on which is the overall best option available. This systematic review investigates the efficacy and safety of different local pharmacological treatments for Achilles tendinopathy. We included only randomized controlled studies (RCTs) focusing on clinical and functional outcomes of therapies consisting in injection of a substance or local application. Assessment of the methodological quality was performed using a modified version of the Coleman methodology score (CMS) to determine possible risks of bias. Thirteen RCTs were included with a total of 528 studied patients. Eleven studies reported the outcomes of injection therapies. Two studies examined the outcomes of patients who applied glyceryl trinitrate patch. The mean modified CMS was 70.6 out of 90. There was no significant evidence of remarkable benefits provided by any of the therapies studied. There is not univocal evidence to advise any particular pharmacological treatment as the best advisable non-operative option for Achilles tendinopathy as equivalent alternative to the most commonly used eccentric loading rehabilitation program. However, potential was shown by the combination of different substances administered with physical therapy. There is a need for more long-term investigations, studying large enough cohort with standardized scores and evaluations shared by all the investigations to confirm the healing potential, and provide a stronger statistical comparison of the available treatments. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:

  20. Melt Adsorption as a Manufacturing Method for Fine Particles of Wax Matrices without Any Agglomerates.

    Shiino, Kai; Fujinami, Yukari; Kimura, Shin-Ichiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru


    We have focused on melt adsorption as manufacture method of wax matrices to control particles size of granules more easily than melt granulation. The purpose of present study was to investigate the possibility of identifying a hydrophobic material with a low melting point, currently used as a meltable binder of melt granulation, to apply as a novel carrier in melt adsorption. Glyceryl monostearate (GM) and stearic acid (SA) were selected as candidate hydrophobic materials with low melting points. Neusilin US2 (US2), with a particle diameter of around 100 µm was selected as a surface adsorbent, while dibasic calcium phosphate dihydrate (DCPD), was used as a non-adsorbent control to prepare melting granules as a standard for comparison. We prepared granules containing ibuprofen (IBU) by melt adsorption or melt granulation and evaluated the particle size, physical properties and crystallinity of granules. Compared with melt granulation using DCPD, melt adsorption can be performed over a wide range of 14 to 70% for the ratio of molten components. Moreover, the particle size; d50 of obtained granules was 100-200 µm, and these physical properties showed good flowability and roundness. The process of melt adsorption did not affect the crystalline form of IBU. Therefore, the present study has demonstrated for the first time that melt adsorption using a hydrophobic material, GM or SA, has the potential capability to control the particle size of granules and offers the possibility of application as a novel controlled release technique.

  1. A theoretical approach to evaluate the release rate of acetaminophen from erosive wax matrix dosage forms.

    Agata, Yasuyoshi; Iwao, Yasunori; Shiino, Kai; Miyagishima, Atsuo; Itai, Shigeru


    To predict drug dissolution and understand the mechanisms of drug release from wax matrix dosage forms containing glyceryl monostearate (GM; a wax base), aminoalkyl methacrylate copolymer E (AMCE; a pH-dependent functional polymer), and acetaminophen (APAP; a model drug), we tried to derive a novel mathematical model with respect to erosion and diffusion theory. Our model exhibited good agreement with the whole set of experimentally obtained values pertaining to APAP release at pH 4.0 and pH 6.5. In addition, this model revealed that the eroding speed of wax matrices was strongly influenced by the loading content of AMCE, but not that of APAP, and that the diffusion coefficient increased as APAP loading decreased and AMCE loading increased, thus directly defining the physicochemical properties of erosion and diffusion. Therefore, this model might prove a useful equation for the precise prediction of dissolution and for understanding the mechanisms of drug release from wax matrix dosage forms. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. EPR investigation of gamma irradiated single crystal guaifenesin: A combined experimental and computational study

    Tasdemir, Halil Ugur; Sayin, Ulku; Türkkan, Ercan; Ozmen, Ayhan


    Gamma irradiated single crystal of Guaifenesin (Glyceryl Guaiacolate), an important expectorant drug, were investigated with Electron Paramagnetic Resonance (EPR) spectroscopy between 123 and 333 K temperature at different orientations in the magnetic field. Considering the chemical structure and the experimental spectra of the gamma irradiated single crystal of guaifenesin sample, we assumed that alkoxy or alkyl-type paramagnetic species may be produced by irradiation. Depending on this assumption, eight possible alkoxy and alkyl-type radicals were modeled and EPR parameters of these modeled radicals were calculated using the B3LYP/6-311++G(d,p)-level of density functional theory (DFT). Theoretically calculated values of alkyl-type modeled radical(R3) are in good agreement with experimentally determined EPR parameters of single crystal. Furthermore, simulation spectra which are obtained by using the theoretical initial values are well matched with the experimental spectra. It was determined that a stable Cα •H2αCβHβCγH2γ (R3) alkyl radical was produced in the host crystal as a result of gamma irradiation.

  3. A monolithic lipase reactor for biodiesel production by transesterification of triacylglycerides into fatty acid methyl esters

    Urban, Jiří T.


    An enzymatic reactor with lipase immobilized on a monolithic polymer support has been prepared and used to catalyze the transesterification of triacylglycerides into the fatty acid methyl esters commonly used for biodiesel. A design of experiments procedure was used to optimize the monolithic reactor with variables including control of the surface polarity of the monolith via variations in the length of the hydrocarbon chain in alkyl methacrylate monomer, time of grafting of 1-vinyl-4,4-dimethylazlactone used to activate the monolith, and time used for the immobilization of porcine lipase. Optimal conditions involved the use of a poly(stearyl methacrylate-co-ethylene dimethacrylate) monolith, grafted first with vinylazlactone, then treated with lipase for 2h to carry out the immobilization of the enzyme. Best conditions for the transesterification of glyceryl tributyrate included a temperature of 37°C and a 10min residence time of the substrate in the bioreactor. The reactor did not lose its activity even after pumping through it a solution of substrate equaling 1,000 reactor volumes. This enzymatic reactor was also used for the transesterification of triacylglycerides from soybean oil to fatty acid methyl esters thus demonstrating the ability of the reactor to produce biodiesel. © 2011 Wiley Periodicals, Inc.

  4. RES and brain targeting stavudine-loaded solid lipid nanoparticles for AIDS therapy

    Panchaxari M Dandagi


    Full Text Available Cells of the reticuloendothelial system (RES, e.g., macrophages play an important role in the immunopathogenesis of Acquired Immunodeficiency Syndrome (AIDS. The objective of the present study was to investigate the possibility of specifically targeting antiviral drugs Stavudine to RES (like Liver, Spleen etc. and brain using solid lipid nanoparticles (SLNs as colloidal drug carriers. Various lipids like stearic acid, cetyl palmitate, glyceryl behenate and phospholipid in combination have been used and effect of lipid on properties of SLNs has been investigated. The SLNs of Stavudine were prepared by double emulsion solvent evaporation method. The diameter of SLNs was determined and found in range of 175 ± 6.027 to 393 ± 2.309 nm depending on the type of lipid used. Percentage drug entrapment was found to be influenced by the concentration and type of lipid used, which was found in the range of 18.1 to 65.2%. The drug release behavior was studied by dialysis bag method and the release pattern of drug was found to follow Higuchi model. Results of stability evaluation showed a relatively long-term stability after storage at 4°C for 1 month. Stavudine-loaded SLNs were successfully prepared, optimized and effectively targeted to RES and brain. SLNs of Stavudine have been shown to be taken up by brain 11 fold greater as compared to pure Stavudine. This finding is more important since Human Immunodeficiency Syndrome (HIV infect the central nervous system.

  5. Combinatorial study of ceramic tape-casting slurries.

    Liu, Zhifu; Wang, Yiling; Li, Yongxiang


    Ceramic tape-casting slurries are complex systems composed of ceramic powder, solvent, and a number of organic components. Conventionally, the development of ceramic tape-casting slurries is time-consuming and of low efficiency. In this work, combinatorial approaches were applied to screen the ethanol and ethyl-acetate binary solvent based slurry for ceramic green tape-casting. The combinatorial libraries were designed considering the variation of the amount of PVB (Poly vinyl-butyral) binder, polyethylene-400, and butyl-benzyl-phthalate plasticizers, and glyceryl triacetate dispersant. A parallel magnetic stirring process was used to make the combinatorial slurry library. The properties mapping of the slurry library was obtained by investigating the sedimentation and rheological characteristics of the slurries. The slurry composition was refined by scaling up the experiments and comparing the microstructure, mechanical property, and sintering behavior of green tapes made from the selected slurries. Finally, a kind of ethanol-ethyl acetate binary solvent based slurry system suitable for making X7R dielectric ceramic green tapes was achieved.

  6. Biotransformation and nitroglycerin-induced effects on antioxidative defense system in rat erythrocytes and reticulocytes.

    Marković, Snežana D; Dorđević, Nataša Z; Curčić, Milena G; Stajn, Andraš S; Spasić, Mihajlo B


    The effects of nitroglycerin (glyceryl trinitrate - GTN) are mediated by liberated nitric oxide (NO) and formed reactive nitrogen species, which induces oxidative stress during biotransformation in red blood cells (RBCs). The aim of this study was to evaluate effects of GTN on antioxidative defense system (AOS) in rat erythrocytes (without) and reticulocytes (with functional mitochondria). Rat erythrocyte and reticulocyte-rich RBC suspensions were aerobically incubated (2 h, 37°C) without (control) or in the presence of different concentrations of GTN (0.1-1.5 mM). After incubation, concentrations of non-enzymatic components of AOS, activities of antioxidative enzymes and oxidative pentose phosphate (OPP) pathway activity were followed in RBC suspensions. In rat reticulocytes, GTN decreased the activity of mitochondrial MnSOD and increased the activity of CuZnSOD. In rat RBCs, GTN induced increase of Vit E concentration (at high doses), but decreased glutathione content and activities of all glutathione-dependent antioxidative enzymes; the OPP pathway activity significantly increased. GTN biotransformation and induction of oxidative stress were followed by general disbalance of antioxidative capacities in both kinds of RBCs. We suggest that oxidative stress, MnSOD inhibition and depletion of glutathione pool in response to GTN treatment lead to decreased bioavailability of NO after GTN biotransformation in rat reticulocytes.

  7. Maintenance Therapy with Partially Hydrolyzed Guar Gum in the Conservative Treatment of Chronic Anal Fissure: Results of a Prospective, Randomized Study

    Antonio Brillantino


    Full Text Available Purpose. This study was designed to evaluate the role of maintenance therapy with partially hydrolyzed guar gum (PHGG after topical application of glyceryl trinitrate (GTN in the conservative treatment of chronic anal fissure (CAF. Methods. From all the patients with CAF observed during the study period, 165 subjects with healed CAF after standard therapy with topical GTN 0.4% ointment were randomized to receive (group II or not (group I maintenance therapy with PHGG for 10 months. Clinical and manometric followup was carried out 6 and 12 months after treatment. Results. At six-month followup, median visual analogue scale score was significantly higher in group I if compared with group II. The success and recurrence rate at 12-month followup were, respectively, 38.3% (28/73 in group I versus 58.5% (41/70 in group II (P=0.019; Fisher’s exact test and 30.2% (13/43 in group I versus 14.5% (7/48 in group II (P=0.0047; Fisher’s exact test. Conclusion. The maintenance therapy with PHGG in patients with healed CAF after chemical sphincterotomy by topical application of GTN 0.4% ointment seems associated with a significant reduction of recurrence rate and with a significant increase of success rate at 12-month followup.

  8. Nitroxyl: a vasodilator of human vessels that is not susceptible to tolerance.

    Andrews, Karen L; Lumsden, Natalie G; Farry, Julie; Jefferis, Ann-Maree; Kemp-Harper, Barbara K; Chin-Dusting, Jaye P F


    Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO•), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and saphenous veins were obtained from patients undergoing coronary artery graft surgery and mounted in organ baths. Repeated vasodilator responses to the HNO donor Angeli's salt (AS) and NO• donor glyceryl trinitrate (GTN) were determined. AS- and GTN-induced concentration-dependent vasorelaxation of both human radial arteries (AS pEC50: 6.5 ± 0.2; -log M) and saphenous veins (pEC50: 6.7 ± 0.1) with similar potency. In human radial arteries, GTN-induced relaxation was reduced by the NO• scavenger hydroxocobalamin (HXC; PGTN in arteries and veins (PGTN, suggesting that the relaxation to both redox congeners is cGMP- and Kv channel-dependent. Critically, a concentration-dependent development of tolerance to GTN (1 and 10 μM; PGTN, the HNO donor AS causes vasorelaxation of human blood vessels via activation of a cGMP-dependent pathway. Unlike GTN, however, it does not develop tolerance in human blood vessels.

  9. Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the "Rapid Intervention with GTN in Hypertensive Stroke Trial" (RIGHT, ISRCTN66434824).

    Ankolekar, Sandeep; Sare, Gillian; Geeganage, Chamila; Fuller, Michael; Stokes, Lynn; Sprigg, Nikola; Parry, Ruth; Siriwardena, A Niroshan; Bath, Philip M W


    Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included. Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited. Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40.

  10. Chronic administration of the HNO donor Angeli's salt does not lead to tolerance, cross-tolerance, or endothelial dysfunction: comparison with GTN and DEA/NO.

    Irvine, Jennifer C; Kemp-Harper, Barbara K; Widdop, Robert E


    Nitroxyl (HNO) displays distinct pharmacology to its redox congener nitric oxide (NO(•)) with therapeutic potential in the treatment of heart failure. It remains unknown if HNO donors are resistant to tolerance development following chronic in vivo administration. Wistar-Kyoto rats received a 3-day subcutaneous infusion of one of the NO(•) donors, glyceryl trinitrate (GTN) or diethylamine/NONOate (DEA/NO), or the HNO donor Angeli's salt (AS). GTN infusion (10 μg/kg/min) resulted in significantly blunted depressor responses to intravenous bolus doses of GTN, demonstrating tolerance development. By contrast, infusion with AS (20 μg/kg/min) or DEA/NO (2 μg/kg/min) did not alter their subsequent depressor responses. Similarly, ex vivo vasorelaxation responses in isolated aortae revealed that GTN infusion elicited a significant 6-fold decrease in the sensitivity to GTN and reduction in the maximum response to acetylcholine (ACh). Chronic infusion of AS or DEA/NO had no effect on subsequent vasorelaxation responses to themselves or to ACh. No functional cross-tolerance between nitrovasodilators was evident, either in vivo or ex vivo, although an impaired ability of a nitrovasodilator to increase tissue cGMP content was not necessarily indicative of a reduced functional response. In conclusion, HNO donors may represent novel therapies for cardiovascular disease with therapeutic potential over clinically used organic nitrates.

  11. Aldehyde dehydrogenase 2 protects human umbilical vein endothelial cells against oxidative damage and increases endothelial nitric oxide production to reverse nitroglycerin tolerance.

    Hu, X Y; Fang, Q; Ma, D; Jiang, L; Yang, Y; Sun, J; Yang, C; Wang, J S


    Medical nitroglycerin (glyceryl trinitrate, GTN) use is limited principally by tolerance typified by a decrease in nitric oxide (NO) produced by biotransformation. Such tolerance may lead to endothelial dysfunction by inducing oxidative stress. In vivo studies have demonstrated that aldehyde dehydrogenase 2 (ALDH2) plays important roles in GTN biotransformation and tolerance. Thus, modification of ALDH2 expression represents a potentially effective strategy to prevent and reverse GTN tolerance and endothelial dysfunction. In this study, a eukaryotic expression vector containing the ALDH2 gene was introduced into human umbilical vein endothelial cells (HUVECs) by liposome-mediated transfection. An indirect immunofluorescence assay showed that ALDH2 expression increased 24 h after transfection. Moreover, real-time polymerase chain reaction and western blotting revealed significantly higher ALDH2 mRNA and protein expression in the gene-transfected group than in the two control groups. GTN tolerance was induced by treating HUVECs with 10 mM GTN for 16 h + 10 min, which significantly decreased NO levels in control cells, but not in those transfected with ALDH2. Overexpression of ALDH2 increased cell survival against GTN-induced cytotoxicity and conferred protection from oxidative damage resulting from nitrate tolerance, accompanied by decreased production of intracellular reactive oxygen species and reduced expression of heme oxygenase 1. Furthermore, ALDH2 overexpression promoted Akt phosphorylation under GTN tolerance conditions. ALDH2 gene transfection can reverse and prevent tolerance to GTN through its bioactivation and protect against oxidative damage, preventing the development of endothelial dysfunction.

  12. Catalysis of nitrite generation from nitroglycerin by glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

    Seabra, Amedea B; Ouellet, Marc; Antonic, Marija; Chrétien, Michelle N; English, Ann M


    Vascular relaxation to nitroglycerin (glyceryl trinitrate; GTN) requires its bioactivation by mechanisms that remain controversial. We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the release of nitrite from GTN. In assays containing dithiothreitol (DTT) and NAD(+), the GTN reductase activity of purified GAPDH produces nitrite and 1,2-GDN as the major products. A vmax of 2.6nmolmin(-)(1)mg(-)(1) was measured for nitrite production by GAPDH from rabbit muscle and a GTN KM of 1.2mM. Reductive denitration of GTN in the absence of DTT results in dose- and time-dependent inhibition of GAPDH dehydrogenase activity. Disulfiram, a thiol-modifying drug, inhibits both the dehydrogenase and GTN reductase activity of GAPDH, while DTT or tris(2-carboxyethyl)phosphine reverse the GTN-induced inhibition. Incubation of intact human erythrocytes or hemolysates with 2mM GTN for 60min results in 50% inhibition of GAPDH's dehydrogenase activity, indicating that GTN is taken up by these cells and that the dehydrogenase is a target of GTN. Thus, erythrocyte GAPDH may contribute to GTN bioactivation.

  13. A monolithic lipase reactor for biodiesel production by transesterification of triacylglycerides into fatty acid methyl esters.

    Urban, Jiri; Svec, Frantisek; Fréchet, Jean M J


    An enzymatic reactor with lipase immobilized on a monolithic polymer support has been prepared and used to catalyze the transesterification of triacylglycerides into the fatty acid methyl esters commonly used for biodiesel. A design of experiments procedure was used to optimize the monolithic reactor with variables including control of the surface polarity of the monolith via variations in the length of the hydrocarbon chain in alkyl methacrylate monomer, time of grafting of 1-vinyl-4,4-dimethylazlactone used to activate the monolith, and time used for the immobilization of porcine lipase. Optimal conditions involved the use of a poly(stearyl methacrylate-co-ethylene dimethacrylate) monolith, grafted first with vinylazlactone, then treated with lipase for 2 h to carry out the immobilization of the enzyme. Best conditions for the transesterification of glyceryl tributyrate included a temperature of 37°C and a 10 min residence time of the substrate in the bioreactor. The reactor did not lose its activity even after pumping through it a solution of substrate equaling 1,000 reactor volumes. This enzymatic reactor was also used for the transesterification of triacylglycerides from soybean oil to fatty acid methyl esters thus demonstrating the ability of the reactor to produce biodiesel.

  14. Use of solid dispersions to increase stability of dithranol in topical formulations

    Marilene Estanqueiro


    Full Text Available The present study was planned to improve the stability of dithranol using solid dispersions (SD. Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature, high temperature exposition (37 °C (protected from light and protected from light (room temperature. Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.

  15. Vasoactive drugs inhibit oxygen radical production of neutrophils.

    Weiss, M; Schneider, E M; Liebert, S; Mettler, S; Lemoine, H


    A concentration response study was performed to clarify whether vasoactive drugs, routinely used in intensive care patients, inhibit oxygen radical production of neutrophils. Moreover, in a cell-free system, it was investigated whether these drugs exert free radical scavenging properties. Vasoactive agents were incubated with neutrophils from healthy human volunteers, which were stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and by opsonized zymosan to produce oxygen radicals, detected by chemiluminescence measurements. Sympathomimetics (epinephrine greater than norepinephrine, dopamine and dobutamine) as well as phosphodiesterase-inhibitors (amrinone and enoximone) inhibited FMLP-induced and zymosan-induced oxygen radical production of neutrophils in a concentration-dependent and drug-specific fashion. With the exception of amrinone, FMLP-induced chemiluminescence of neutrophils was impaired nearly 10-fold more markedly than zymosan-induced chemiluminescence. Glyceryl trinitrate, nifedipine and prostacyclin had no effect on oxygen radical production of neutrophils. In the cell-free system, epinephrine, norepinephrine, dopamine, amrinone and enoximone demonstrated oxygen free radical scavenging properties. This study shows that vasoactive drugs, frequently used in the clinical setting, may suppress oxidative burst after FMLP-receptor stimulation. As demonstrated in the cell-free system, this suppression was, at least in part, due to oxygen radical scavenging.

  16. Uso de inotropos y vasodilatadores en la comunicación interventricular

    Lincoln de la Parte Pérez


    Full Text Available Se realiza un estudio retrospectivo en 92 lactantes operados de comunicación interventricular en el Cardiocentro del Hospital Pediátrico Docente "William Soler", durante el período de 1989 a 1993. La dobutamina fue el inotrópico más utilizado (67 pacientes, así como la nitroglicerina resultó ser el vasodilatador de preferencia (76 pacientes, 82,60 %. Las arritmias cardíacas constituyeron la complicación más frecuente (55, 59, 78 % y el síndrome de bajo gasto cardíaco tuvo una incidencia del 13 %. No hubo fallecidos durante el transoperatorio.A retrospective study is carried out in 92 infants operated of interventricular communication, in the Cardiocenter of the "William Soler" Educational Pediatric Hospital, during 1989-1993. Dobutamine was the most used inotropic (67 patients, and glyceryl trinitrate was the preferred vasodilator (76 patients, 82,60 %. Cardiac arrhytmias were the most frequent complications (55,59,78 % and the low cardiac output syndrome had an incidence of 13 %. There were no deceased children during the transoperative.

  17. Supercritical carbon dioxide interpolymer complexes improve survival of B. longum Bb-46 in simulated gastrointestinal fluids.

    Thantsha, Mapitsi S; Cloete, Thomas E; Moolman, Francis S; Labuschagne, Philip W


    Gastric acidity is the main factor affecting viability of probiotics in the gastrointestinal tract (GIT). This study investigated the survival in simulated gastrointestinal fluids of Bifidobacterium longum Bb-46 encapsulated in interpolymer complexes formed in supercritical carbon dioxide (scCO(2)). Bacteria were exposed sequentially to simulated gastric fluid (SGF, pH 2) for 2 h and simulated intestinal fluid (SIF, pH 6.8) for 6 or 24 h. Total encapsulated bacteria were determined by suspending 1 g of product in SIF for 6 h at 37 degrees C prior to plating out. Plates were incubated anaerobically at 37 degrees C for 72 h. The interpolymer complex displayed pH-responsive release properties, with little to no release in SGF and substantial release in SIF. There was a limited reduction in viable counts at the end of exposure period due to encapsulation. Protection efficiency of the interpolymer complex was improved by addition of glyceryl monostearate (GMS). Gelatine capsules delayed release of bacteria from the interpolymer complex thus minimizing time of exposure to the detrimental conditions. Use of poly(caprolactone) (PCL), ethylene oxide-propylene oxide triblock copolymer (PEO-PPO-PEO) decreased the protection efficiency of the matrix. Interpolymer complex encapsulation showed potential for protection of probiotics and therefore for application in food and pharmaceuticals.

  18. Impact of anti-tacking agents on properties of gas-entrapped membrane and effervescent floating tablets.

    Kriangkrai, Worawut; Puttipipatkhachorn, Satit; Sriamornsak, Pornsak; Pongjanyakul, Thaned; Sungthongjeen, Srisagul


    Tackiness caused by the gas-entrapped membrane (Eudragit(®)RL 30D) was usually observed during storage of the effervescent floating tablets, leading to failure in floatation and sustained release. In this work, common anti-tacking agents (glyceryl monostearate (GMS) and talc) were used to solve this tackiness problem. The impact of anti-tacking agent on the properties of free films and corresponding floating tablets was investigated. GMS was more effective than talc in reducing tackiness of the film. Addition and increasing amount of anti-tacking agents lowered the film mechanical strength, but the coating films were still strong and flexible enough to resist the generated gas pressure inside the floating tablet. Wettability and water vapor permeability of the film decreased with increasing level of anti-tacking agents as a result of their hydrophobicity. No interaction between anti-tacking agents and polymer was observed as confirmed by Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry studies. Increasing amount of anti-tacking agents decreased time to float and tended to retard drug release of the floating tablets. Floating properties and drug release were also influenced by type of anti-tacking agents. The obtained floating tablets still possessed good floating properties and controlled drug release even though anti-tacking agent had some effects. The results demonstrated that the tackiness problem of the floating tablets could be solved by incorporating anti-tacking agent into the gas-entrapped membrane.

  19. Defensive Armor of Potato Tubers: Nonpolar Metabolite Profiling, Antioxidant Assessment, and Solid-State NMR Compositional Analysis of Suberin-Enriched Wound-Healing Tissues.

    Dastmalchi, Keyvan; Kallash, Linda; Wang, Isabel; Phan, Van C; Huang, Wenlin; Serra, Olga; Stark, Ruth E


    The cultivation, storage, and distribution of potato tubers are compromised by mechanical damage and suboptimal healing. To investigate wound-healing progress in cultivars with contrasting russeting patterns, metabolite profiles reported previously for polar tissue extracts were complemented by GC/MS measurements for nonpolar extracts and quantitative (13)C NMR of interfacial solid suspensions. Potential marker compounds that distinguish cultivar type and wound-healing time point included fatty acids, fatty alcohols, alkanes, glyceryl esters, α,ω-fatty diacids, and hydroxyfatty acids. The abundant long-chain fatty acids in nonpolar extracts and solids from the smooth-skinned Yukon Gold cultivar suggested extensive suberin biopolymer formation; this hypothesis was supported by high proportions of arenes, alkenes, and carbonyl groups in the solid and among the polar markers. The absence of many potential marker classes in nonpolar Atlantic extracts and interfacial solids suggested a limited extent of suberization. Modest scavenging activities of all nonpolar extracts indicate that the majority of antioxidants produced in response to wounding are polar.

  20. Effect of Coating Method on the Survival Rate of L. plantarum for Chicken Feed.

    Lee, Sang-Yoon; Jo, Yeon-Ji; Choi, Mi-Jung; Lee, Boo-Yong; Han, Jong-Kwon; Lim, Jae Kag; Oh, Jae-Wook


    This study was designed to find the most suitable method and wall material for microencapsulation of the Lactobacillus plantarum to maintain cell viability in different environmental conditions. To improve the stability of L. plantarum, we developed an encapsulation system of L. plantarum, using water-in-oil emulsion system. For the encapsulation of L. plantarum, corn starch and glyceryl monostearate were selected to form gel beads. Then 10% (w/v) of starch was gelatinized by autoclaving to transit gel state, and cooled down at 60ºC and mixed with L. plantarum to encapsulate it. The encapsulated L. plantarum was tested for the tolerance of acidic conditions at different temperatures to investigate the encapsulation ability. The study indicated that the survival rate of the microencapsulated cells in starch matrix was significantly higher than that of free cells in low pH conditions with relatively higher temperature. The results showed that corn starch as a wall material and glycerol monostearate as a gelling agent in encapsulation could play a role in the viability of lactic acid bacteria in extreme conditions. Using the current study, it would be possible to formulate a new water-in-oil system as applied in the protection of L. plantarum from the gastric conditions for the encapsulation system used in chicken feed industry.

  1. Determining the Feasibility of Ambulance-Based Randomised Controlled Trials in Patients with Ultra-Acute Stroke: Study Protocol for the “Rapid Intervention with GTN in Hypertensive Stroke Trial” (RIGHT, ISRCTN66434824)

    Ankolekar, Sandeep; Sare, Gillian; Geeganage, Chamila; Fuller, Michael; Stokes, Lynn; Sprigg, Nikola; Parry, Ruth; Siriwardena, A. Niroshan; Bath, Philip M. W.


    Background. Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments. No completed randomised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK, and the practicalities of recruiting, consenting, and treating patients are unknown. Methods. RIGHT is an ambulance based, single-blind, randomised controlled trial with blinded-outcome assessment. The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments; a secondary aim is to assess the effect of glyceryl trinitrate (GTN) on haemodynamic variables and functional outcomes. Initial consent, randomisation, and treatment are performed by paramedics prior to hospitalisation. Patients with ultra-acute stroke (≤4 hours of onset) are randomised to transdermal GTN (5 mg/24 hours) or gauze dressing daily for 7 days. The primary outcome is systolic blood pressure at 2 hours. Secondary outcomes include feasibility, haemodynamics, dependency, and other functional outcomes. A nested qualitative study is included. Trial Status. The trial has all relevant ethics and regulatory approvals and recruitment started on February 15, 2010. The trial stopped recruitment in December 2011 after 41 patients were recruited. Trial Registration. The trial registration number is ISRCTN66434824 and EudraCT number is 2007-004766-40. PMID:23125943

  2. Process and formulation variables in the preparation of wax microparticles by a melt dispersion technique. I. Oil-in-water technique for water-insoluble drugs.

    Bodmeier, R; Wang, J; Bhagwatwar, H


    Ibuprofen-wax (carnauba, paraffin, beeswax, and the semisynthetic glyceryl esters--Gelucire 64/02 and Precirol ATO5) microparticles were prepared without organic solvents as an alternative to polymeric microparticles. In the melt dispersion technique, the drug-wax melt was emulsified into a heated aqueous phase followed by cooling to form the microparticles. The microparticles were characterized with respect to their drug loading, and morphological and release properties. They were spherical and non-agglomerated and drug loading close to 60 per cent were achieved. The more hydrophilic waxes (Gelucire 64/02 or Precirol ATO5) could be prepared without the use of surfactants. With the other waxes, increasing amounts of sodium lauryl sulphate in the external aqueous phase decreased the drug loading because of drug solubilization when compared to the polymeric stabilizer, poly(vinyl alcohol). The type of wax, the rate of cooling, and the temperature of the aqueous phase had no significant effect on the drug loading because of the low solubility of the drug in the external aqueous phase. The drug release was controlled by the hydrophobicity of the wax. Besides ibuprofen, other water-soluble drugs (ketoprofen, indomethacin, hydrocortisone) were also encapsulated by this method. The wax microparticles could be formulated into an aqueous sustained-release oral suspension dosage form.

  3. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg and Evaluation of Their Antioxidant Activity

    Maria Iorizzi


    Full Text Available Dragon’s blood (Sangre de drago, a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae, is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-β-O-4’- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods (1H-, 13C- NMR and 2D-NMR experiments, ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex exhibited the highest antioxidant activity.

  4. Supercritical fluid precipitation of ketoprofen in novel structured lipid carriers for enhanced mucosal delivery--a comparison with solid lipid particles.

    Gonçalves, V S S; Matias, A A; Rodríguez-Rojo, S; Nogueira, I D; Duarte, C M M


    Structured lipid carriers based on mixture of solid lipids with liquid lipids are the second generation of solid lipid particles, offering the advantage of improved drug loading capacity and higher storage stability. In this study, structured lipid carriers were successfully prepared for the first time by precipitation from gas saturated solutions. Glyceryl monooleate (GMO), a liquid glycerolipid, was selected in this work to be incorporated into three solid glycerolipids with hydrophilic-lipophilic balance (HLB) ranging from 1 to 13, namely Gelucire 43/01™, Geleol™ and Gelucire 50/13™. In general, microparticles with a irregular porous morphology and a wide particle size distribution were obtained. The HLB of the individual glycerolipids might be a relevant parameter to take into account during the processing of solid:liquid lipid blends. As expected, the addition of a liquid lipid into a solid lipid matrix led to increased stability of the lipid carriers, with no significant modifications in their melting enthalpy after 6 months of storage. Additionally, Gelucire 43/01™:GMO particles were produced with different mass ratios and loaded with ketoprofen. The drug loading capacity of the structured lipid carriers increased as the GMO content in the particles increased, achieving a maximum encapsulation efficiency of 97% for the 3:1 mass ratio. Moreover, structured lipid carriers presented an immediate release of ketoprofen from its matrix with higher permeation through a mucous-membrane model, while solid lipid particles present a controlled release of the drug with less permeation capacity.

  5. Preparation and physicochemical properties of surfactant-free emulsions using electrolytic-reduction ion water containing lithium magnesium sodium silicate.

    Okajima, Masahiro; Wada, Yuko; Hosoya, Takashi; Hino, Fumio; Kitahara, Yoshiyasu; Shimokawa, Ken-ichi; Ishii, Fumiyoshi


    Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.

  6. In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell lines

    Shenoy, Vikram S.; Gude, Rajiv P.; Murthy, Rayasa S. Ramachandra


    The present study is aimed to investigate the formulation and in vitro anticancer activities of solid lipid nanoparticles (SLNs) of 5-fluorouracil (5-FU) prepared using glyceryl monostearate (GMS) and cetyl palmitate (CP) by hot homogenization method. The lipids were selected based on the partition coefficient of 5-FU in lipids. The lipid nanoparticles were optimized for process and formulation parameters. The optimized nanoparticles were characterized for their zeta potential, morphology, release kinetics, and anticancer activity. Higher entrapments were achieved using a combination of emulsifiers. The zeta potential of the optimized CP and GMS SLN formulation were -8.26 and -9.35 mV, respectively. Both the optimized formulations were spherical. The in vitro release studies of SLNs of both the lipid carriers followed Peppas-Korsenmeyer equation when carried out at pH 3.5 and 7.4. The chemosensitivity assay carried out in B16F10 cell lines revealed that CP SLNs had better cytotoxicity than 5-FU solution and GMS SLNs at 48 h of incubation. Subtoxic concentration of 5-FU-loaded CP SLNs (0.12 μg/mL) possessed comparable antimigrational activity, colony inhibition activity, and cytopathic as that of 5-FU solution effects. The results indicated that encapsulating 5-FU in CP would be a promising delivery system for delivering 5-FU.

  7. The Influence of Endothelial Function and Myocardial Ischemia on Peak Oxygen Consumption in Patients with Coronary Artery Disease

    Simon L. Bacon


    Full Text Available Impaired endothelial function has been shown to limit exercise in coronary artery disease (CAD patients and has been implicated in myocardial ischemia. However, the association of endothelial function and ischemia on peak exercise oxygen consumption (VO2 has not been previously reported. A total of 116 CAD patients underwent standard exercise stress testing, during which VO2 was measured. On a separate day, endothelial-dependent and -independent function were assessed by ultrasound using flow-mediated arterial vasodilation (FMD and sublingual glyceryl trinitrate administration (GTNMD of the brachial artery. Patients with exercise-induced myocardial ischemia had lower FMD than nonischemic patients (3.64±0.57 versus 4.98±0.36, P=.050, but there was no difference in GTNMD (14.11±0.99 versus 15.47±0.63, P=.249. Analyses revealed that both FMD (P=.006 and GTNMD (P=.019 were related to peak VO2. However, neither the presence of ischemia (P=.860 nor the interaction of ischemia with FMD (P=.382 and GTNMD (P=.151 was related to peak VO2. These data suggest that poor endothelial function, potentially via impaired NO production and smooth muscle dysfunction, may be an important determinant of exercise capacity in patients with CAD, independent of myocardial ischemia.

  8. In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

    Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E


    The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

  9. Effects of Supplemental Exogenous Emulsifier on Performance, Nutrient Metabolism, and Serum Lipid Profile in Broiler Chickens

    Amitava Roy


    Full Text Available The effects of an exogenous emulsifier, glyceryl polyethylene glycol ricinoleate, on performance and carcass traits of broiler chickens were assessed. The emulsifier was added to the diet at dose rates of 0 (control, 1 (E1 and 2 (E2 % of added fat (saturated palm oil. Live weight gain (<.07 and feed conversion ratio (<.05 in 39 days were higher in the E1 dietary group. Gain: ME intake and gain: protein intake during the grower phase improved quadratically (<.05. Gross carcass traits were not affected. Body fat content and fat accretion increased (<.05 and liver fat content decreased (<.05 linearly with the level of emulsifier in diet. Fat excretion decreased (<.001 leading to increased ileal fat digestibility (<.06 in the E1 group (quadratic response. Metabolizable intake of N (<.1 and fat (<.05 increased quadratically due to supplementation of emulsifier in diet. Metabolism of trace elements and serum lipid profiles were not affected. The study revealed that supplementation of exogenous emulsifiers in diets containing moderate quantities of added vegetable fats may substantially improve broiler performance.

  10. Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns

    Thakkar, Vaishali; Korat, Vaishali; Baldaniya, Lalji; Gohel, Mukesh; Gandhi, Tejal; Patel, Nirav


    Introduction: The aim of burn management and therapy is fast healing and epithelisation to prevent infection. The present study is concerned with the development and characterization of a novel nanaoparticulate system; cubosomes, loaded with silver sulfadiazine (SSD) and Aloe vera for topical treatment of infected burns. Methods: Cubosome dispersions were formulated by an emulsification technique using different concentrations of a lipid phase Glyceryl Monooleate (GMO) and Poloxamer 407. The optimum formulae were incorporated in an aloe vera gel containing carbopol 934, to form cubosomal hydrogels (cubogels). The cubogels were characterized by in vitro release of SSD, rheological properties, pH, bioadhesion, Transmission Electron Microscopy and in-vivo Wound Healing Study. Results: The results show that the different concentration of GMO had significant effect on particle size, % EE and in vitro drug release. From the in-vitro drug release pattern and similarity factor (f2), it was concluded that batch CG3 (15% GMO and 1% P407) exhibited complete and controlled drug release within 12 hour (i.e. 98.25%), better bio adhesion and superior burn healing as compared to the marketed product. Conclusion: The in vivo burns healing study in rats revealed that the prepared optimized cubogel containing SSD and aloe vera has superior burns healing rate than cubogel with only SSD and marketed preparation so, it may be successfully used in the treatment of deep second degree burn. PMID:27606259

  11. Contact allergy to ingredients of hair cosmetics - a comparison of female hairdressers and clients based on IVDK 2007-2012 data.

    Uter, Wolfgang; Gefeller, Olaf; John, Swen Malte; Schnuch, Axel; Geier, Johannes


    Cosmetics for bleaching, waving/relaxing and dyeing hair contain well-known allergens, leading to a substantial number of cases of allergic contact dermatitis. To compare the frequency of important contact allergens (i) between two distinct groups of exposed patients, and (ii) with previous surveillance data. On the basis of data collected by the Information Network of Departments of Dermatology (IVDK; between 2007 and 2012 in 824 female hairdressers and 2067 female clients, the current spectrum of contact sensitization to ingredients of hair cosmetics, as contained in different pertinent series, is described. A similar burden of sensitization as in previous analyses was observed, but with some increase in sensitization to oxidative hair dye components in clients. Some allergens mainly affected hairdressers, such as ammonium persulfate (18.7% positive) and glyceryl monothioglycolate (GMTG; still 4.7% positive, with a few cases also in young hairdressers, despite removal from the German market). Hair dyes remain important contact allergens, despite various attempts by the cosmetic industry to introduce hair dyes with lower allergenic potential. The re-emergence of GMTG as an occupational allergen should be considered as a warning signal ('sentinel event') prompting close monitoring. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Excision Hemorrhoidectomy: New Methods to Improve the Outcomes of an Old Technique



    Full Text Available Context Hemorrhoidal disease is the most common anorectal disorder that requires surgical intervention. Hemorrhoids require treatment when they result in symptoms such as bleeding or prolapse. Surgical intervention is indicated for significant prolapse, and a number of accepted and viable methods are available for treating prolapsing hemorrhoids that do not reduce spontaneously (Grade III and IV. Excision hemorrhoidectomy remains the gold standard treatment for Grade III and IV hemorrhoids despite great interest in alternative procedures such as stapled hemorrhoidopexy and Doppler-guided hemorrhoidal artery ligation with mucopexy. A large body of evidence demonstrates that excision hemorrhoidectomy is an effective, safe, and affordable procedure. Nevertheless, the main drawback of excision hemorrhoidectomy remains its notorious association with significant postoperative pain. Evidence Acquisition A comprehensive literature search was conducted through MEDLINE and the Cochrane database of systematic reviews. Only prospective case-controlled studies, review articles, and meta-analyses were considered. Results Many strategies have been put forward in the literature to address the issue of pain after excision hemorrhoidectomy. These strategies can be broadly categorized into surgical techniques (e.g., LigaSure hemorrhoidectomy and pharmacological adjuncts (e.g., intradermal methylene blue and chemical sphincterotomy with glyceryl trinitrate ointment. In recent years, meta-analyses and randomized controlled trials have been performed to evaluate their effects. Conclusions This article evaluates the evidence behind these strategies and outlines the new methods available to improve the outcomes of an old technique.

  13. Determination of fatty acid methyl esters derived from algae Scenedesmus dimorphus biomass by GC-MS with one-step esterification of free fatty acids and transesterification of glycerolipids.

    Avula, Satya Girish Chandra; Belovich, Joanne M; Xu, Yan


    Algae can synthesize, accumulate and store large amounts of lipids in its cells, which holds immense potential as a renewable source of biodiesel. In this work, we have developed and validated a GC-MS method for quantitation of fatty acids and glycerolipids in forms of fatty acid methyl esters derived from algae biomass. Algae Scenedesmus dimorphus dry mass was pulverized by mortar and pestle, then extracted by the modified Folch method and fractionated into free fatty acids and glycerolipids on aminopropyl solid-phase extraction cartridges. Fatty acid methyl esters were produced by an optimized one-step esterification of fatty acids and transesterification of glycerolipids with boron trichloride/methanol. The matrix effect, recoveries and stability of fatty acids and glycerolipids in algal matrix were first evaluated by spiking stable isotopes of pentadecanoic-2,2-d2 acid and glyceryl tri(hexadecanoate-2,2-d2 ) as surrogate analytes and tridecanoic-2,2-d2 acid as internal standard into algal matrix prior to sample extraction. Later, the method was validated in terms of lower limits of quantitation, linear calibration ranges, intra- and inter-assay precision and accuracy using tridecanoic-2,2-d2 acid as internal standard. The method developed has been applied to the quantitation of fatty acid methyl esters from free fatty acid and glycerolipid fractions of algae Scenedesmus dimorphus. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Amylose-lipid complexes as controlled lipid release agents during starch gelatinization and pasting.

    Gelders, Greta G; Goesaert, Hans; Delcour, Jan A


    The effect of amylose-lipid (AM-L) complexes consisting of amylose populations with different peak degrees of polymerization (DP) and complexed with glyceryl monostearate (GMS) or docosanoic acid (C22) on the pasting properties of wheat and rice starches was evaluated with a rapid visco analyzer (RVA). AM-L complexes were formed by both (i) addition of lipids to amylose fractions with peak DP 20, 60, 400, or 950 at 60 degrees C or (ii) potato phosphorylase-catalyzed amylose synthesis in the presence of lipids. All AM-L complexes affected pasting properties in line with their dissociation characteristics. AM-L complexes therefore have potential as "controlled lipid release agents" with effects markedly different from those observable with emulsifier addition in starch pasting. More in particular, short chain AM-L complexes resulted in a starch pasting behavior comparable to that of cross-linked starch, as evidenced by reduced granule swelling, good viscosity stability in conditions of high temperature and shear, and a stable cold paste viscosity.


    D.V. Gowda


    Full Text Available This research work was done to design oral controlled release matrix pellets of water insoluble drug Clozapine, using blend of Hydroxypropyl cellulose and glyceryl palmito stearate as as matrix polymers, methyl crystalline cellulose as spheronizer enhancer,sodium lauryl sulphate as pore forming agent. Clozapine formulations developed by the pellitization technique by drug loaded pellets were characterized with regard to the drug content, size distribution, Scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and Xray Diffraction study. Stability studies were carried out on the optimized formulation for aperiod of 90 days, 40 ± 2 oC and 75 ± 5% relative humidity. The drug content was in the range of 95.34 – 98.12 %. The mean particle size of drug loaded pellets was in the range 1018 to 1065 mm. SEM photographs and calculated sphericity factor confirms that the prepared formulations were spherical in nature. The drug loaded pellets were stable and compatible as confirmed by DSC and FTIR studies. XRD patterns revealed the crystalline nature of pure clozapine. Loose surface crystal study indicated that crystalline clozapine was observed in all formulation and more clear in formulation A5. Higher amount of clozapine released was observed from formulation A5 and Syclop® 25 mg tablet as compared to all other formulations and mechanism of drug release followed Fickian diffusion. It can be concluded that formulation A5 is an ideal formulation for once a day administration.

  16. Novel process of fermenting black soybean [Glycine max (L.) Merrill] yogurt with dramatically reduced flatulence-causing oligosaccharides but enriched soy phytoalexins.

    Feng, Shengbao; Saw, Chin Lee; Lee, Yuan Kun; Huang, Dejian


    Black soybeans [Glycine max (L.) Merrill] were germinated under fungal stress with food grade R. oligosporus for 3 days and were homogenized and fermented with lactic acid bacteria (LAB) to produce soy yogurt. Fungal stress led to the generation of oxylipins [oxooctadecadienoic acids (KODES) isomers and their respective glyceryl esters] and glyceollins--a type of phytoalexins unique to soybeans. In soy yogurt, the concentrations of total KODES and total glyceollins were 0.678 mg/g (dry matter) and 0.953 mg/g, respectively. The concentrations of other isoflavones (mainly genistein and daidzein and their derivatives) in soy yogurt remained largely unchanged after the processes compared with the control soy yogurt. Germination of black soybean under fungal stress for 3 days was sufficient to reduce stachyose and raffinose (which cause flatulence) by 92 and 80%, respectively. With a pH value of 4.42, a lactic acid content of 0.262%, and a maximum viable cell count of 2.1 x 10 (8) CFU/mL in the final soy yogurt, soy milk from germinated soybeans under fungal stress was concluded to be a suitable medium for yogurt-making. The resulting soy yogurt had significantly altered micronutrient profiles with significantly reduced oligosaccharides and enriched glyceollins.

  17. Preparation, characterization, pharmacokinetics and tissue distribution of solid lipid nanoparticles loaded with tetrandrine.

    Li, Su; Ji, Zhaoshuai; Zou, Meijuan; Nie, Xin; Shi, Yijie; Cheng, Gang


    Tetrandrine (TET) is a poorly water-soluble bisbenzylisoquinoline alkaloid. In this study, TET solid lipid nanoparticles (SLNs) were prepared by a melt-emulsification and ultrasonication technique. Precirol(®) ATO 5, glyceryl monostearate, and stearic acid were used as the lipid matrix for the SLNs, while Lipoid E80, Pluronic F68, and sodium deoxycholate were used as emulsifying and stabilizing agents. The physicochemical characteristics of the TET-SLNs were investigated when it was found that the mean particle size and zeta potential of the TET-SLNs were 134 ± 1.3 nm and -53.8 ± 1.7 mV, respectively, and the entrapment efficiency (EE) was 89.57% ± 0.39%. Differential scanning calorimetry indicated that TET was in an amorphous state in SLNs. TET-SLNs exhibited a higher release rate at a lower pH and a lower release rate at a higher pH. The release pattern of the TET-SLNs followed the Weibull model. The pharmacokinetics of TET-SLNs after intravenous administration to male rats was studied. TET-SLN resulted in a higher plasma concentration and lower clearance. The biodistribution study indicated that TET-SLN showed a high uptake in reticuloendothelial system organs. In conclusion, TET-SLNs with a small particle size, and high EE, can be produced by the method described in this study. The SLN system is a promising approach for the intravenous delivery of tetrandrine.

  18. Mono- and tri-ester hydrogenolysis using tandem catalysis. Scope and mechanism.

    Lohr, Tracy L.; Li, Zhi; Assary, Rajeev S.; Curtiss, Larry A.; Marks, Tobin J.


    The scope and mechanism of thermodynamically leveraged ester RC(O)O-R' bond hydrogenolysis by tandem metal triflate + supported Pd catalysts are investigated both experimentally and theoretically by DFT and energy span analysis. This catalytic system has a broad scope, with relative cleavage rates scaling as, tertiary 4 secondary 4 primary ester at 1 bar H-2, yielding alkanes and carboxylic acids with high conversion and selectivity. Benzylic and allylic esters display the highest activity. The rate law is nu = k[M(OTf )(n)](1)[ester](0)[H-2](0) with an H/D kinetic isotope effect = 6.5 +/- 0.5, implying turnover-limiting C-H scission following C-O cleavage, in agreement with theory. Intermediate alkene products are then rapidly hydrogenated. Applying this approach with the very active Hf(OTf)(4) catalyst to bio-derived triglycerides affords near-quantitative yields of C-3 hydrocarbons rather than glycerol. From model substrates, it is found that RC(O)O-R' cleavage rates are very sensitive to steric congestion and metal triflate identity. For triglycerides, primary/external glyceryl CH2-O cleavage predominates over secondary/internal CH-O cleavage, with the latter favored by less acidic or smaller ionic radius metal triflates, raising the diester selectivity to as high as 48% with Ce(OTf)(3).

  19. Structure-interfacial properties relationship and quantification of the amphiphilicity of well-defined ionic and non-ionic surfactants using the PIT-slope method.

    Ontiveros, Jesús F; Pierlot, Christel; Catté, Marianne; Molinier, Valérie; Salager, Jean-Louis; Aubry, Jean-Marie


    The Phase Inversion Temperature of a reference C10E4/n-Octane/Water system exhibits a quasi-linear variation versus the mole fraction of a second surfactant S2 added in the mixture. This variation was recently proposed as a classification tool to quantify the Hydrophilic-Lipophilic Balance (HLB) of commercial surfactants. The feasibility of the so-called PIT-slope method for a wide range of well-defined non-ionic and ionic surfactants is investigated. The comparison of various surfactants having the same dodecyl chain tail allows to rank the polar head hydrophilicity as: SO3Na⩾SO4Na⩾NMe3Br>E2SO3Na≈CO2Na⩾E1SO3Na⩾PhSO3Na>Isosorbide(exo)SO4Na≫IsosorbideendoSO4Na≫E8⩾NMe2O>E7>E6⩾Glucosyl>E5⩾Diglyceryl⩾E4>E3>E2≈Isosorbide(exo)>Glyceryl>Isosorbide(endo). The influence on the surfactant HLB of other structural parameters, i.e. hydrophobic chain length, unsaturation, replacement of Na(+) by K(+) counterion, and isomerism is also investigated. Finally, the method is successfully used to predict the optimal formulation of a new bio-based surfactant, 1-O-dodecyldiglycerol, when performing an oil scan at 25 °C.

  20. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

    Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B


    In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  1. Can migraine aura be provoked experimentally? A systematic review of potential methods for the provocation of migraine aura.

    Lindblad, Marianne; Hougaard, Anders; Amin, Faisal Mohammad; Ashina, Messoud


    Background The nature of the migraine aura and its role in migraine pathophysiology is incompletely understood. In particular, the mechanisms underlying aura initiation and the causal relation between aura and headache are unknown. The scientific investigation of aura in patients is only possible if aura can be triggered. This paper reviews potential methods for the experimental provocation of migraine aura. Methods We systematically searched PubMed for studies of experimental migraine provocation, including case reports of patients with aura and reports of the occurrence of aura following exposure to any kind of suspected trigger. Results We identified 21 provocation studies, using 13 different prospective provocation methods, and 34 case reports. In the prospective studies, aura were reported following the administration of intravenous and sublingual glyceryl trinitrate, visual stimulation, physical activity, calcitonin gene-related peptide infusion, chocolate ingestion, and the intravenous injection of insulin. In addition, carotid artery puncture has consistently been reported as a trigger of aura. Conclusions No safe and efficient method for aura provocation exists at present, but several approaches could prove useful for this purpose.

  2. Biodiesel synthesis using calcined layered double hydroxide catalysts

    Schumaker, J. Link [University of Kentucky; Crofcheck, Czarena [University of Kentucky; TAckett, S. Adam [University of Kentucky; Santillan-Jimenez, Eduardo [University of Kentucky; Morgan, Tonya [University of Kentucky; Ji, Yaying [University of Kentucky; Crocker, Mark [University of Kentucky; Toops, Todd J [ORNL


    The catalytic properties of calcined Li-Al, Mg-Al and Mg-Fe layered double hydroxides (LDHs) were examined in two transesterification reactions, namely, the reaction of glyceryl tributyrate with methanol, and the reaction of soybean oil with methanol. While the Li-Al catalysts showed high activity in these reactions at the reflux temperature of methanol, the Mg-Fe and Mg-Al catalysts exhibited much lower methyl ester yields. CO2 TPD measurements revealed the presence of sites of weak, medium and strong basicity on both Mg-Al and Li-Al catalysts, the latter showing higher concentrations of medium and strong base sites; by implication, these are the main sites active in transesterification catalyzed by calcined Li-Al LDHs. Maximum activity was observed for the Li-Al catalysts when a calcination temperature of 450-500 aC was applied, corresponding to decomposition of the layered double hydroxide to the mixed oxide without formation of crystalline lithium aluminate phases.

  3. Synthesis and Preliminary Investigations of the siRNA Delivery Potential of Novel, Single-Chain Rigid Cationic Carotenoid Lipids

    Philip L. Leopold


    Full Text Available The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethanecarbamoyl]-cholesterol (DC-Chol and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC as positive controls. All cationic lipids (controls and single-chain lipids were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE. Cationic lipid-siRNA complexes of varying (+/− molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/− molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.

  4. Phosphorus NMR of isolated perfused morris hepatomas

    Graham, R.A.; Meyer, R.A.; Brown, T.R.; Sauer, L.A.


    The authors are developing techniques for the study of perfused solid tumors by NMR. Tissue-isolated solid hepatomas were grown to 1-2 cm diameter as described previously. The arterial supply was isolated and the tumors perfused (0.5 - 1.0 ml/min) in vitro at 25 C with a 15% suspension of red blood cells in Krebs-Henseliet solution. /sup 31/P-NMR spectra were acquired at 162 MHz in a specially-designed NMR probe using a solenoidal coil. Intracellular pH (monitored from the chemical shift of inorganic phosphate) and ATP levels were stable for up to 6 hrs during perfusion. During 30 min of global ischemia, ATP decreased by 75% and pH fell from 7.0 to 6.7. These changes were reversed by 1 hr reperfusion. In addition to ATP and phosphate, the spectra included a large resonance due to phosphomonoesters, as well as peaks consistent with glycerylphosphocholine, glyceryl-phosphoethanolamine, phosphocreatine, NAD, and UDPG. However, the most novel feature of the spectra was the presence of an unidentified peak in the phosphonate region (+ 16.9 ppm). The peak was not present in spectra of muscle, liver, brain, kidney, or fat tissues excised from the same animals. They are presently attempting to identify the compound that gives rise to this peak and to establish its metabolic origin.

  5. Neuromyogenic properties of the internal anal sphincter: therapeutic rationale for anal fissures.

    Bhardwaj, R; Vaizey, C J; Boulos, P B; Hoyle, C H


    Lateral sphincterotomy diminishes internal anal sphincter hypertonia and thereby reduces anal canal pressure. This improves anal mucosal blood flow and promotes the healing of anal fissures. However, sphincterotomy can be associated with long term disturbances of sphincter function. The optimal treatment for an anal fissure is to induce a temporary reduction of anal canal resting pressure to allow healing of the fissure without permanently disrupting normal sphincter function. Broader understanding of the intrinsic mechanisms controlling smooth muscle contraction has allowed pharmacological manipulation of anal sphincter tone. We performed an initial Medline literature search to identify all articles concerning "internal anal sphincter" and "anal fissures". This review is based on these articles and on additional publications obtained by manual cross referencing. Internal anal smooth muscle relaxation can be inhibited by stimulation of non-adrenergic non-cholinergic enteric neurones, parasympathetic muscarinic receptors, or sympathetic beta adrenoceptors, and by inhibition of calcium entry into the cell. Sphincter contraction depends on an increase in cytoplasmic calcium and is enhanced by sympathetic adrenergic stimulation. Currently, the most commonly used pharmacological agent in the treatment of anal fissures is topical glyceryl trinitrate, a nitric oxide donor. Alternative agents that exhibit a similar effect via membrane Ca2+ channels, muscarinic receptors, and alpha or beta adrenoceptors are also likely to have a therapeutic potential in treating anal fissures.

  6. St. John's wort reversal of meningeal nociception: a natural therapeutic perspective for migraine pain.

    Galeotti, N; Ghelardini, C


    Despite a number of antimigraine drugs belonging to different pharmacological classes are available, there is a huge unmet need for better migraine pharmacotherapy. We here demonstrated the capability of Hypericum perforatum, popularly called St. John's wort (SJW), to relieve meningeal nociception in an animal model induced by administration of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). GTN and SNP produced a delayed meningeal inflammation, as showed by the upregulation of interleukin (IL)-1β and inducible NO synthase (iNOS), and a prolonged cold allodynia and heat hyperalgesia with a time-course consistent with NO-induced migraine attacks. A single oral administration of a SJW dried extract (5mg/kg p.o.) counteracted the nociceptive behaviour and the overexpression of IL-1β and iNOS. To clarify the cellular pathways involved, the expression of protein kinase C (PKC) and downstream effectors was detected. NO donors increased expression and phosphorylation of PKCγ, PKCɛ and transcription factors, such as nuclear factor (NF)-κB, cyclic AMP response element binding protein (CREB), Signal Transducer and Activator of Transcription (STAT)-1. All these molecular events were prevented by SJW and hypericin, a SJW main component. In conclusion, SJW counteracted the NO donor-induced pain hypersensitivity and meningeal activation by blocking PKC-mediated pathways involving NF-κB, CREB, STAT1. These results might suggest SJW as an innovative and safe perspective for migraine pain.

  7. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

    Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica


    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.

  8. In vitro release studies of piroxicam from oil-in-water creams and hydroalcoholic gel topical formulations.

    Rafiee-Tehrani, M; Mehramizi, A


    The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37 degrees C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.

  9. Role of Met93 and Thr96 in the lid hinge region of Rhizopus chinensis lipase.

    Zhu, Shan-Shan; Li, Ming; Yu, Xiaowei; Xu, Yan


    We engineered Rhizopus chinensis lipase to study its critical amino acid role in catalytic properties. Based on the amino acid sequence and three-dimensional model of the lipase, residues located in its lid hinge region (Met93 and Thr96) were replaced with corresponding amino acid residues (Ile93 and Asn96) found in the lid hinge region of Rhizopus oryzae lipase. The substitutions in the lid hinge region affected not only substrate specificity but also the thermostability of the lipase. Both lipases preferred p-nitrophenyl laurate and glyceryl trilaurate (C12). However, the variant S4-3O showed a slight decline in activity toward long-chain fatty acid (C16-C18). When enzymes activities decreased by half, the temperature of the variant (45 °C) was 22 °C lower than the parent (67 °C), probably substantially destabilized the structure of the lid region. The interfacial kinetic analysis of S4-3O suggested that the lower catalytic efficiency was due to a higher K m* value. According to the lipase structure investigated, Ile93Met played a role of narrowing the size of the hydrophobic patch, which affected the substrate binding affinity, and Asn96Thr destabilized the structure of the lipase by disrupting the H-bond interaction in the lid region.

  10. Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol.

    Patil, Sharvil S; Roy, Krishtey; Choudhary, Bhavana; Mahadik, Kakasaheb R


    In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3(2) Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as Cmax, Tmax, Ke, Ka, Vd and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in Cmax (two fold, p GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.

  11. Conférence Chevreul

    Mouloungui Zéphirin


    Full Text Available In this study two major strategy of transformation of the vegetables substrate are exposed. The first approach is related to the study of the catalytic heterocyclisation of natural glycerin in the glycerol carbonate. The system glycerol/glycerol carbonate constitutes a reactional medium of synthon generation and chemical compounds with skelton of multipurpose glycerylic. Glycerol carbonate is a molecule of first generation of the glycerol, it is conceived in natural media as a new chemistry which makes it possible to reinject glycerol in existing or new industry from the orginal procedure by the way of chemical means. The second approach regards the oleaginous seeds, as substrate in vitro or as microreactor in vivo. This marks a technological breakage compared to the model and tradional process of prapartion of oleochemical bases. In this matter it seems possible to obtain the fatty acids, fatty esters, directly from the oleaginous seeds by interaction between lipids and functional enzymes. This quantitave experimental approach produces the free hydrophobic moity and guarantees the multifonctionnal oleophiles compounds from the renewable oleochemistry.

  12. Intraoral film containing insulin-phospholipid microemulsion: formulation and in vivo hypoglycemic activity study.

    Rachmawati, Heni; Haryadi, Bernard Manuel; Anggadiredja, Kusnandar; Suendo, Veinardi


    Non-invasive administration of insulin is expected for better diabetes mellitus therapy. In this report, we developed intraoral preparation for insulin. Insulin was encapsulated into nanocarrier using self-assembly emulsification process. To increase lipophilicity of insulin, it was dispersed in phospholipid resulted in insulin-phospholipid solid dispersion. The microemulsion formula was established from our previous work which contained glyceryl monooleate (GMO), Tween 20, and polyethylene glycol (PEG 400) in a ratio of 1:8:1. To confirm the formation of insulin-phospholipid solid dispersion, PXRD, FTIR spectroscopy, and Raman spectroscopy were performed. Then, the microemulsion was evaluated for droplet size and distribution, zeta potential, entrapment efficiency, physical stability, and Raman spectroscopy. In addition, microemulsion with expected characteristic was evaluated for in vitro release, in vitro permeation, and in vivo activity. The droplets size of ∼100 nm with narrow distribution and positive charge of +0.56 mV were formed. The insulin encapsulated in the oil droplet was accounted of >90%. Water-soluble chitosan seems to be a promising film matrix polymer which also functioned as insulin release controller. Oral administration of insulin microemulsion to healthy Swiss-Webster mice showed hypoglycemic effect indicating the success of this protein against a harsh environment of the gastrointestinal tract. This effectiveness significantly increased by fourfold as compared to free insulin. Taken together, microemulsion seems to be a promising carrier for oral delivery of insulin.

  13. A novel liquid effervescent floating delivery system for sustained drug delivery.

    Ibrahim, H K


    An effervescent floating liquid formulation with in situ gelling properties has been assessed for its potential for sustaining drug delivery and targeting. The formulation consisted of sodium alginate and glyceryl monooleate (GMO). The developed formulation met all pre-requisites to become an in situ gelling floating system and it gelled and floated instantaneously in the pH conditions of the stomach. Moreover, the gels formed in situ remained intact for more than 48 h to facilitate sustained release of drugs. Increasing the mannuronic acid ratio of sodium alginate and the GMO concentration significantly retarded the release rate and extent. The in vitro release of both hydrophilic and hydrophobic drugs from the prepared formulations followed root-time kinetics during the sustained release period. Replacing the free drug with drug encapsulated microspheres enabled tailoring of the release profile and achieved zero-order release kinetics. The system retained its appearance and rheological properties for 12 months at ambient conditions. The values of the similarity factor Sd proved the absence of any significant difference in the release profile upon storage.

  14. Kinetics of carrier-mediated ion transport in two new types of solvent-free lipid bilayers.

    Lapointe, J Y; Laprade, R


    In contrast with the usual glyceryl-monooleate/decane (GMO-D) bilayer lipid membranes, new membranes, formed from a mixture of GMO in squalene (GMO-S) or from a mixture of GMO in triolein (GMO-T), seem to be almost solvent free. Our results from voltage-jump relaxation studies, using these "solvent-free" membranes with the homologue carriers, nonactin, monactin, dinactin, trinactin, and tetranactin, are compared with the corresponding ones for GMO-D membranes. With all homologues, solvent-free membranes show an increase of the free carrier translocation rate, ks, by a factor of 2.5, a decrease in the dissociation rate constant of the complex, kDi, by a factor of 1.5 and no significant change in its formation rate constant, kRi. However, the principal effect of the absence of solvent in these membranes is an increase by a factor of approximately 10 of the translocation rate constant for moving the complex across the membrane, kis. This increase varies regularly from a factor of 7-15 with decreasing carrier size, and is always larger for GMO-T than for GMO-S membranes. These solvent-free effects are interpreted in terms of modifications of electrostatic and hydrophobic energy profiles in the membrane.

  15. A novel in situ gel for sustained drug delivery and targeting.

    Ganguly, Sudipta; Dash, Alekha K


    The objective of this study was to develop a novel chitosan-glyceryl monooleate (GMO) in situ gel system for sustained drug delivery and targeting. The delivery system consisted of 3% (w/v) chitosan and 3% (w/v) GMO in 0.33M citric acid. In situ gel was formed at a biological pH. In vitro release studies were conducted in Sorensen's phosphate buffer (pH 7.4) and drugs were analyzed either by HPLC or spectrophotometry. Characterization of the gel included the effect of cross-linker, determination of diffusion coefficient and water uptake by thermogravimetric analysis (TGA). Mucoadhesive property of the gel was evaluated in vitro using an EZ-Tester. Incorporation of a cross-linker (glutaraldehyde) retarded the rate and extent of drug release. The in vitro release can further be sustained by replacing the free drug with drug-encapsulated microspheres. Drug release from the gel followed a matrix diffusion controlled mechanism. Inclusion of GMO enhanced the mucoadhesive property of chitosan by three- to sevenfold. This novel in situ gel system can be useful in the sustained delivery of drugs via oral as well as parenteral routes.

  16. Rapid and sensitive measurements of nitrate ester explosives using microchip electrophoresis with electrochemical detection.

    Piccin, Evandro; Dossi, Nicolò; Cagan, Avi; Carrilho, Emanuel; Wang, Joseph


    This article describes an effective microchip protocol based on electrophoretic-separation and electrochemical detection for highly sensitive and rapid measurements of nitrate ester explosives, including ethylene glycol dinitrate (EGDN), pentaerythritol tetranitrate (PETN), propylene glycol dinitrate (PGDN) and glyceryl trinitrate (nitroglycerin, NG). Factors influencing the separation and detection processes were examined and optimized. Under the optimal separation conditions obtained using a 15 mM borate buffer (pH 9.2) containing 20 mM SDS, and applying a separation voltage of 1500 V, the four nitrate ester explosives were separated within less than 3 min. The glassy-carbon amperometric detector (operated at -0.9 V vs. Ag/AgCl) offers convenient cathodic detection down to the picogram level, with detection limits of 0.5 ppm and 0.3 ppm for PGDN and for NG, respectively, along with good repeatability (RSD of 1.8-2.3%; n = 6) and linearity (over the 10-60 ppm range). Such effective microchip operation offers great promise for field screening of nitrate ester explosives and for supporting various counter-terrorism surveillance activities.

  17. 可生物降解的环保型镁合金微乳化切削液的制备%Preparation of biodegradable environmental-friendly micro-emulsion cutting fluid for magnesium alloys

    陈郁明; 周建辉; 周玉成; 孙雪飞


    A biodegradable environmental-friendly micro-emulsion cutting fluid for magnesium alloys was developed. The influence of base oil, corrosion inhibitor, chelator, anti-rust agent, lubricant, surfactant, and other additives on lubrication property of the cutting fluid were studied. The optimal formulation was determined as follows: naphthenic base oil 30.0wt%, modified organic alcohol chelator 1.5wt%, composite corrosion inhibitor 2.5wt%, triethanolamine 8.0wt%, long carbon chain polycarboxylic acid anti-rust agent 5.0wt%, polymerized glycerol trioleate lubricant 16.0wt%, polyoleate lubricant 6.0wt%, AEO fatty alcohol polyoxyethylene ether surfactant 2.5wt%, emulsion-type low-foam fatty alcohol polyoxyethylene ether surfactant 3.0wt%, fungicide 1.0wt%, defoamer 0.1wt%, and water 24.4wt%. In comparison with the marketable commercial products of Castrol and Master, the developed micro-emulsion cutting fluid for magnesium alloys has lower price but better performance in aspects of lubrication, hard water resistance, anti-corrosion, defoamation, and service life. Its biodegradation rate is 92.0% and hard water resistance reaches 8 330 mg/L. The green and highly efficient micro-emulsion cutting fluid is a special-purpose cutting fluid for magnesium alloys.%开发了一种可生物降解的环保型镁合金微乳化切削液,考察了基础油、缓蚀剂、螯合剂、防锈剂、润滑剂、表面活性剂和其他添加剂对切削液润滑性能的影响,筛选出最优的微乳化切削液配方(以质量分数表示):环烷基基础油30.0%,改性有机醇类螯合剂1.5%,复合缓蚀剂2.5%,三乙醇胺8.0%,长碳链多元羧酸防锈剂5.0%,聚合油酸合成酯润滑剂16.0%,多元油酸合成酯润滑剂6.0%,AEO类脂肪醇聚氧乙烯醚表面活性剂2.5%,脂肪醇聚氧乙烯醚类乳化型低泡表面活性剂3.0%,杀菌剂1.0%,消泡剂0.1%,水24.4%。所开发的镁合金微乳化切削液在润滑、抗硬水、防腐防锈、

  18. Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D–phospholipid complex

    Shen J


    Full Text Available Jinyang Shen,1 Jianping Bi,2 Hongli Tian,1 Ye Jin,1 Yuan Wang,3 Xiaolin Yang,4 Zhonglin Yang,1 Junping Kou,5 Fei Li1 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 2Shandong Provincial Traditional Chinese Medical Hospital & Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 3Traditional Chinese Medical Hospital of Pukou District, 4Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine, 5Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People’s Republic of China Background: Akebia saponin D (ASD exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD.Methods: ASD–phospholipid complex (APC was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats.Results: The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n-octanol. Peceol (Glyceryl

  19. Long-term stability investigation of o/w cosmetic creams stabilized by mixed emulsifier

    Đekić Ljiljana M.


    Full Text Available Polyglyceryl-3 Methylglucose Distearate (PMD, TEGO® Care 450, Evonik, Germanyis natural (vegetable, non-ionic, PEG-free emulsifier, suitable for the formulation of oil-in-water (o/w cosmetic creams and lotions. The oil phase components can be selected from mineral oils, vegetable oils and synthetic esters, which enable different variety of application profile of these emulsions. It is possible to prepare stable emulsions using low-level concentration of the PMD (2-3% if lotions contain 10-25%, and creams 20-40 % of oil phase. PMD forms liquid crystal structure in the presence of stearic acid, glyceryl stearate, fatty alcohols, or their combinations. The o/w type creams, stabilized by these mixed emulsifiers are complex, multiphase systems. The aim of this work was to formulate, prepare and investigate long-term stability of the o/w creams stabilized by mixed emulsifier polyglyceryl-3 methylglucose distearate/glyceryl stearate/stearyl alcohol, depending on concentration levels of PMD (2% or 3% and oil:water phase ratio (20:80 and 30:70. The samples were prepared using hot/hot procedure. Organoleptic inspection, centrifugation test, rheological measurements, electric conductivity and pH value measurements were performed 72 h, 1, 3, 12 and 30 months after preparation. The prepared samples were apparently white and homogenous creams. The consistency and homogeneity were preserved after centrifugation of the creams after 72 h, 1, 3, 12 and 30 months storage, and no phase separation could be detected. The pH values obtained are suitable for skin application. Conductivity values (25.2-63.7 μS cm1, 72 h after preparation were attributed to the multiple phase o/w emulsions with high percentages of fixed water. Results of the rheological measurements have shown that the investigated creams exhibited non-Newtonian thyxotropic behavior. The concentration of emulsifier PMD and oil phase content had an influence on the rheological parameters of investigated

  20. Preparation and characterization of loperamide-loaded Dynasan 114 solid lipid nanoparticles for increased oral absorption in the treatment of diarrhea

    Lili Wei


    Full Text Available The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN formulations for oral delivery of loperamide (LPM to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114 nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug, were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering (DLS. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope (TEM and a scanning electron microscope (SEM. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227% and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

  1. In vitro comparative evaluation of monolayered multipolymeric films embedded with didanosine-loaded solid lipid nanoparticles: a potential buccal drug delivery system for ARV therapy.

    Jones, Elsabé; Ojewole, Elizabeth; Kalhapure, Rahul; Govender, Thirumala


    Drug delivery via the buccal route has emerged as a promising alternative to oral drug delivery. Didanosine (DDI) undergoes rapid degradation in the gastrointestinal tract, has a short half-life and low oral bioavailability, making DDI a suitable candidate for buccal delivery. Recent developments in buccal drug delivery show an increased interest toward nano-enabled delivery systems. The advantages of buccal drug delivery can be combined with that of nanoparticulate delivery systems to provide a superior delivery system. The aim of this study was to design and evaluate the preparation of novel nano-enabled films for buccal delivery of DDI. Solid lipid nanoparticles (SLNs) were prepared via hot homogenization followed by ultrasonication and were characterized before being incorporated into nano-enabled monolayered multipolymeric films (MMFs). Glyceryl tripalmitate with Poloxamer 188 was identified as most suitable for the preparation of DDI-loaded SLNs. SLNs with desired particle size (PS) (201 nm), polydispersity index (PDI) (0.168) and zeta potential (-18.8 mV) were incorporated into MMFs and characterized. Conventional and nano-enabled MMFs were prepared via solvent casting/evaporation using Eudragit RS100 and hydroxypropyl methylcellulose. Drug release from the nano-enabled films was found to be faster (56% versus 20% in first hour). Conventional MMFs exhibited higher mucoadhesion and mechanical strength than nano-enabled MMFs. SLNs did not adversely affect the steady state flux (71.63 ± 13.54 µg/cm(2) h versus 74.39 ± 15.95 µg/cm(2) h) thereby confirming the potential transbuccal delivery of DDI using nano-enabled MMFs. Nano-enabled buccal films for delivery of DDI can be successfully prepared, and these physico-mechanical studies serve as a platform for future formulation optimization work in this emerging field.

  2. Co-encapsulation of multi-lipids and polymers enhances the performance of vancomycin in lipid-polymer hybrid nanoparticles: In vitro and in silico studies.

    Seedat, Nasreen; Kalhapure, Rahul S; Mocktar, Chunderika; Vepuri, Suresh; Jadhav, Mahantesh; Soliman, Mahmoud; Govender, Thirumala


    Nano-drug delivery systems are being widely explored to overcome the challenges with existing antibiotics to treat bacterial infections [1]. Lipid-polymer hybrid nanoparticles (LPNs) display unique advantages of both liposomes and polymeric nanoparticles while excluding some of their limitations, particularly the structural integrity of the polymeric particles and the biomimetic properties of the liposome [1]. The use of helper lipids and polymers in LPNs has not been investigated, but has shown potential in other nano-drug delivery systems to improve drug encapsulation, antibacterial activity and drug release. Therefore, LPNs using co-excipients were prepared using vancomycin (VCM), glyceryl triplamitate and Eudragit RS100 as the drug, lipid and polymer respectively. Oleic acid (OA), Chitosan (CHT) and Sodium alginate (ALG) were explored as co-excipients. Results indicated rod-shaped LPNs with suitable size, PDI and zeta potential, while encapsulation efficiency (%EE) increased from 27.8% to 41.5%, 54.3% and 69.3% with the addition of OA, CHT and ALG respectively. Drug release indicated that VCM-CHT had the best performance in sustained drug release of 36.1 ± 5.35% after 24h. The EE and drug release were further corroborated by in silico and release kinetics data. In vitro antibacterial studies of all formulations exhibited better activity against bare VCM and sustained activity up to day 5 against both Staphylococcus aureus and MRSA, with VCM-OA and VCM-CHT showing better activity against MRSA. Therefore, this LPN proves to be a promising system for delivery of VCM as well as other antibiotics.

  3. Formulation Optimization of Rosuvastatin Calcium-Loaded Solid Lipid Nanoparticles by 32 Full-Factorial Design

    Kruti A. Dhoranwala


    Full Text Available The present investigation was aimed at developing Rosuvastatin Calcium loaded solid lipid nanoparticles (SLNs. The SLNs were prepared using high pressure homogenization technique. Glyceryl monostearate (GMS and Poloxamer 188 were employed as lipid carrier and surfactant respectively. A two factor, three level (32 full factorial design was applied to study the effect of independent variables i.e. amount of GMS (X1 and amount of Poloxamer 188 (X2 on dependent variables i.e. Particle size (Y1 and % entrapment efficiency (Y2. Particles size, % entrapment efficiency (%EE, zeta potential, drug content, in vitro drug release and particles morphology were evaluated for SLNs. Contour plots and response surface plots showed visual representation of relationship between the experimental responses (dependent variables and the set of input (independent variables. The adequacy of the regression model was verified by a check point analysis. The optimized batch (B10 contained 2.2 gm of GMS and 1% of Poloxamer 188. Batch B 10 exhibited mean particle size of 529.6 nm ± 6.36 nm; polydispersity index (PDI of 0.306 ± 0.042; zeta potential of -31.88 mV ± (-2.50 mV and %EE of 48.90% ± 1.72%. The drug release experiments exhibited an initial rapid release followed by sustained release extended upto 36 h. Differential scanning calorimetry (DSC studies showed that there was no chemical interaction between drug (Rosuvastatin Calcium and lipid (GMS whereas scanning electron microscopy (SEM studies indicated that Rosuvastatin Calcium loaded SLNs are spherical, discrete and homogenous. Accelerated stability studies showed that there was no significant change occurring in the responses after storage for a total period of 3 months.

  4. Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.

    Winter, D C


    PURPOSE: The use of transanal stapling devices may impair continence because of digital dilatation and\\/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion. METHODS: A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography. RESULTS: Intraoperative mean (+\\/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +\\/- 0.9 vs. 50.5 +\\/- 2.7; P = 0.002) or controls (56.0 +\\/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +\\/- 3.2 - 31.6 +\\/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +\\/- 0.2 vs. 4.6 +\\/- 0.3; P = 0.003) and 12-month (0.9 +\\/- 0.1 vs. 4.4 +\\/- 0.3; P = 0.002) clinic visits. CONCLUSION: Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.

  5. Evaluation of the "added value" of SIMS: A mass spectrometric and spectroscopic study of an unusual Naples yellow oil paint reconstruction

    Keune, Katrien; Hoogland, Frank; Boon, Jaap J.; Peggie, David; Higgitt, Catherine


    Naples yellow-containing oil paints aged under natural and artificial conditions were investigated as model systems to evaluate the potential of secondary ion mass spectrometry (SIMS) when used in combination with other mass spectrometric and spectroscopic analytical methods. Although the advantage of SIMS is the simultaneous detection of organic and inorganic components and their spatial distribution, the methodology has limitations in compound sensitivity and shows bias towards certain constituents. Gas chromatography-mass spectrometry (GC/MS) shows dicarboxylic fatty acids to be main components in the paint, but SIMS detects these compounds poorly. Electrospray ionisation mass spectrometry (ESI-MS) shows a broad range of glyceryl derivatives of mono- and dicarboxylic fatty acids (mono-, di- and triglyceride derivatives), while SIMS only detects the mono- and diglycerides of the monocarboxylic acids. Compared to SIMS, direct temperature-resolved mass spectrometry (DTMS) offers greater insight into how the various constituents are incorporated into the paint film, but SIMS data supports the information provided by Fourier transform infrared (FTIR) on metal soap formation. The surface sensitivity of SIMS is an advantage for probing paint constituent distributions and was exploited to examine variations in the composition of the top and bottom of a paint film, and the spatial correlation between metal and fatty acid composition in metal soap aggregates. Disadvantages of SIMS are the low yields and matrix dependency of the organic species in the paint matrix. Application of an ultra-thin gold coating overcomes this, and enhances the organic secondary ion yields leading to more accurate spatial distribution.

  6. Preparation and Characterization of Liranaftate Solid Lipid Nanoparticles%利拉萘酯固体脂质纳米粒的构建及表征

    张海龙; 刘海乐; 兰天; 丁劲松


    Solid lipid nanoparticles (SLN) loaded with liranaftate were prepared by emulsion solvent diffusion method with glyceryl monostearate and cholesterin as matrix material. The formulation was optimized through orthogonal design. The mean particle size of the liranaftate SLN was (145.3±6.1)nm with the entrapment efficiency of (75.8±0.7) % and drug loading of (4.82±0.03) %. The results of differential scanning calorimetry (DSC) showed that liranaftate was entrapped in the SLN as amorphous form. The results of preliminary stability test showed that the liranaftate SLN stored at 4℃ for 30 d could maintain stable. The results of in vitro transdermal test showed that the skin deposition ratio of liranaftate SLN gel was about 100 times of the commercial cream (Zefnart).%以单硬脂酸甘油酯和胆固醇为脂质材料,采用乳化溶剂扩散法制备利拉萘酯固体脂质纳米粒,并采用正交设计优化处方.结果表明,所得优化制品平均粒径为(145.3±6.1)nm,包封率为(75.8±0.7)%,载药量为(4.82±0.03)%,DSC分析提示药物可能以无定形状态存在于载体中.稳定性初步研究显示制品在4℃条件放置30 d可维持稳定.体外透皮试验表明,利拉萘酯固体脂质纳米粒凝胶的皮肤滞留比约为市售乳膏(Zefnart)的100倍.

  7. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin


    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea. PMID:27708583

  8. 响应面法优化高压均质制备DHA固体脂质纳米粒%Preparation of DHA solid lipid nanoparticles by high pressure homogenization using response surface methodology

    胡本涛; 王玉堂; 张振; 黄宇; 刘宁


    The easily oxidized docosahexaenoic acid (DHA) was protected by solid lipid nanoparticles ( SLN) . Glyceryl monostearate was used as wall material and DHA algal oil was used as core material to prepare DHA - SLN by high pressure homogenization. The technological parameters were optimized by response surface methodology on the basis of single factor experiment with DHA - SLN embedding rate as response value. The optimal technological parameters were as follows: ratio of core material to wall material 1: 65, homogenization pressure 80 MPa, mass fraction of emulsifier 2. 14% (based on aqueous phase), homogenization times 8. Under these conditions, the embedding rate of DHA - SLN was 74. 45%.%采用固体脂质纳米粒保护容易氧化的二十二碳六烯酸(DHA).以单硬脂酸甘油酯为壁材,DHA藻油为芯材,采用高压均质制备DHA固体脂质纳米粒(DHA-SLN).以DHA-SLN的包封率为指标,通过单因素实验和响应面法优化工艺参数,得出高压均质法制备DHA-SLN的最佳工艺条件是:芯壁比1∶65,均质压力80 MPa,乳化剂质量分数2.14%(占水相),均质8次.在此条件下,实验验证的DHA-SLN的包封率为74.45%.

  9. [Results of patch test in hairdressers examined in the institute of occupational medicine in Łódź].

    Kieć-Swierczyńska, Marta; Krecisz, Beata; Chomiczewska, Dorota


    Occupational contact dermatitis is a significant health problem in hairdressers. The number of occupational skin diseases in this group constantly increases. The most frequent factors contributing to the skin damage include water, shampoos, detergents, conditioners, hair dyes, bleaches, permanent wave solutions, and components of gloves. A group of 121 hairdressers (106 women and 6 men) was selected from 4523 patients (2996 women and 1527 men) referred to the Nofer Institute of Occupational Medicine, Łódź, in 1995-2008, with suspected occupational skin disease. All hairdressers underwent dermatological examination and allergy tests (patch tests with allergens of the European Standard Series and Hairdressing Series, Chemotechnique Diagnostics, Sweden; skin prick tests, Allergopharma, Germany). Females were more prevalent than males and constituted 94.6% of the study group. Of all the study participants, 30% were trainee hairdressers. At least one positive patch test reaction was found in 69.7% of patients whereas in 30.3% patch tests were negative. The most frequent contact allergens were: nickel sulfate (40% of females), p-phenylenediamine (one fourth of the study group), ammonium persulfate (23.2%), cobalt chloride (21.4%), 2,5-diaminotoluene sulfate (9.8%), formaldehyde (9.8%), ammonium thioglycolate (7.1%), and glyceryl monothioglycolate (7.1%). Moreover, we found positive patch test reactions to thimerosal (14.3%), palladium chloride (11.6%), potassium dichromate (5.3%) and fragrance mix (4.5%). Altogether, occupational origin of skin disease was confirmed in 46.4% of hairdressers with allergic contact dermatitis, in 48.2% of those diagnosed with irritant contact dermatitis and in 0.9% of hairdressers suffering from urticaria. 71% of trainee hairdressers were finally diagnosed with allergic contact dermatitis, caused first of all by ammonium persulfate, p-phenylenediamine, nickel and thimerosal. In conclusion, it seems to be indispensable to implement health

  10. Monolithic stationary phases with incorporated fumed silica nanoparticles. Part I. Polymethacrylate-based monolithic column with incorporated bare fumed silica nanoparticles for hydrophilic interaction liquid chromatography.

    Aydoğan, Cemil; El Rassi, Ziad


    Fumed silica nanoparticles (FSNPs), were incorporated for the first time into a polymethacrylate monolithic column containing glyceryl monomethacrylate (GMM) and ethylene dimethacrylate (EDMA) in order to develop a new monolithic column for hydrophilic interaction high performance liquid chromatography (HILIC). When compared to poly(GMM-EDMA) monolithic column without FSNPs, the same monolithic column with incorporated FSNPs yielded important effects on HILIC separations. The effects of monomers and FSNPs content of the polymerization mixture on the performance of the monolithic column were examined in details, and the optimized stationary phase was investigated over a wide range of mobile phase composition with polar acidic, weakly basic and neutral analytes including hydroxy benzoic acids, nucleotides, nucleosides, dimethylformamide, formamide and thiourea. The retention of these analytes was mainly controlled by hydrophilic interactions with the FSNPs and electrostatic repulsion from the negatively charged silica surface in the case of hydroxy benzoic acids and nucleotides. The electrostatic repulsion was minimized by decreasing the pH of the aqueous component of the mobile phase, which in turn enhanced the retention of acidic solutes. Nucleotides were best separated using step gradient elution at decreasing pH as well as ACN concentration in the mobile phase. Improved peak shape and faster analysis of nucleosides were attained by a fast linear gradient elution with a shallow decrease in the ACN content of the ACN-rich mobile phase. The run-to-run and column-to-column reproducibility were satisfactory. The percent relative standard deviations (%RSDs) for the retention times of tested solutes were lower than 2.5% under isocratic conditions and lower than 3.5 under gradient conditions.

  11. Monolithic stationary phases with incorporated fumed silica nanoparticles. Part II. Polymethacrylate-based monolithic column with "covalently" incorporated modified octadecyl fumed silica nanoparticles for reversed-phase chromatography.

    Aydoğan, Cemil; El Rassi, Ziad


    This study is concerned with the incorporation of surface modified fumed silica nanoparticles (FSNPs) into polymethacrylate based monolithic columns for use in reversed phase chromatography (RPC) of small solutes and proteins. First, FSNPs were modified with 3-(trimethoxysilyl)propylmethacrylate (TMSPM) to yield the "hybrid" methacryloyl fumed silica nanoparticle (MFSNP) monomer. The resulting MFSNP was then mixed with glyceryl monomethacrylate (GMM) and ethylene dimethacrylate (EDMA) in a binary porogenic solvent composed of cyclohexanol and dodecanol, and the in situ copolymerization of MFSNP, GMM and EDMA was performed in a stainless steel column of 4.6 mm i.d. The silanol groups of the hybrid monolith thus obtained were grafted with octadecyl ligands by perfusing the hybrid monolithic column with a solution of 4% w/v of dimethyloctadecylchlorosilane (DODCS) in toluene while the column was maintained at 110°C for 6h (in a heated HPLC oven). One of the originalities of this study was to demonstrate MFSNP as a novel derivatized "hybrid monomer" in making RPC monolithic columns with surface bound octadecyl ligands. In this respect, the RPC behavior of the monolithic column with "covalently" incorporated FNSPs having surface grafted octadecyl ligands was evaluated with alkylbenzenes, aniline derivatives and phenolic compounds. The results showed that the hybrid poly(GMA-EDMA-MFSNP) having surface bound octadecyl ligands exhibited hydrophobic interactions under reversed phase elution conditions. Furthermore, six standard proteins were baseline separated on the column using a 10min linear gradient elution at increasing ACN concentration in the mobile phase at a flow rate of 1.0mL/min using a 10 cm×4.6mm i.d. column. The relative standard deviations (RSDs) for the retention times of the tested solutes were lower than 2.1% and 2.4% under isocratic elution and gradient elution conditions, respectively.

  12. Hexagonal boron nitride as a tablet lubricant and a comparison with conventional lubricants.

    Uğurlu, Timuçin; Turkoğlu, Murat


    The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) as a new tablet lubricant and compare it with conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl behenate (COMP). Tablets were manufactured on an instrumented single-station tablet press to monitor lower punch ejection force (LPEF) containing varied lubricants in different ratio (0.5, 1, 2%). Tablet crushing strength, disintegration time and thickness were measured. Tensile strength of compacted tablets were measured by applying a diametrical load across the edge of tablets to determine mechanical strength. The deformation mechanism of tablets was studied during compression from the Heckel plots with or without lubricants. MGST was found to be the most effective lubricant based on LPEF-lubrication concentration profile and LPEF of HBN was found very close to that of MGST. HBN was better than both STAC and COMP. A good lubrication was obtained at 0.5% for MGST and HBN (189 and 195N, respectively). Where COMP and STAC showed 20 and 35% more LPEF compare to that of MGST (239 and 288N, respectively). Even at the concentration of 2% COMP and STAC did not decrease LPEF as much as 0.5% of MGST and HBN. Like all conventional lubricants the higher the concentration of HBN the lower the mechanical properties of tablets because of its hydrophobic character. However, this deterioration was not as pronounced as MGST. HBN had no significant effect on tablet properties. Based on the Heckel plots, it was observed that after the addition of 1% lubricant granules showed less plastic deformation.

  13. Effects of lubricants on binary direct compression mixtures.

    Uğurlu, T; Halaçoğlu, M D; Türkoğlu, M


    The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant on binary direct compression mixtures. Magnesium stearate (MGST), stearic acid (STAC), glyceryl behenate (COMP) and hexagonal boron nitride (HBN) were tested. The binary mixtures were 1:1 combinations of spray dried lactose (FlowLac 100), dicalcium phosphate dihydrate (Emcompress), and modified starch (Starch 1500) with microcrystalline cellulose (Avicel PH 102). Tablets were manufactured on a single-station instrumented tablet press with and without lubricants. In the case of unlubricated granules, the modified starch-microcrystalline cellulose mixture provided the highest percent compressibility value at 8.25%, spray dried lactose-microcrystalline cellulose mixture was 7.33%, and the dialcium phosphate dihydrate-microcrystalline cellulose mixture was 5.79%. Their corresponding tablet crushing strength values were: 104 N, 117 N, and 61 N, respectively. The lubricant concentrations studied were 0.5, 1, 2, and 4%. Effects of lubricant type and lubricant concentration on crushing strength were analyzed using a factorial ANOVA model. It was found that the Avicel PH 102-Starch 1500 mixture showed the highest lubricant sensitivity (110 N vs. 9 N), the least affected formulation was FlowLac-Avicel PH 102 mixture (118 N vs. 62 N). The crushing strength vs. concentration curve for MGST showed a typical biphasic profile, a fast drop up to 1% and a slower decline between 1 and 4%. The STAC, COMP, and HBN for all formulations showed a shallow linear decline of tablet crushing strength with increasing lubricant concentration. The HBN was as effective as MGST as a lubricant, and did not show a significant negative effect on the crushing strength of the tablets. The COMP and STAC also did not interfere with the crushing strength, however, they were not as effective lubricants as MGST or HBN.

  14. Research of improved formula of crystal moon cake crust%水晶月饼饼皮制作配方的改良研究

    钱庆银; 芮汉明; 潘柯伊; 张立彦


    The effect of wheat starch, glyceryl monostearate (GMS) and guar gum on hardness, weight decrease and sensory quality of crystal moon cake crust were researched. The results showed that: hardness increased while the proportion of wheat starch increasing. Less than 0.3% GMS added could slow aging degree, but more than 0.3% would lead to aging degree increase. Less than 1% guar gum added could slow aging degree and improve transparency. But more than 1% would lead to aging degree increase, samples had granular and sensation. Through orthogonal experiment came out the optimal formulation: wheat starch 38.19%,acetylated starch 19.1%,cassava starch 41.81%,GMS 0.1%,guar gum 1%.%研究了澄粉、单甘脂、瓜尔豆胶的不同添加量对水晶月饼饼皮的硬度、重量、感官品质的影响.结果表明,随着澄粉加入比例的增加,样品的硬度逐渐增大.单甘脂量低于0.3%时能延缓老化,当过量时会引起饼皮过软、老化加快.瓜尔豆胶量低于1%时可以延缓老化、提高透明度,高于1%时老化加快并且有颗粒感.通过正交实验确定水晶月饼饼皮的最优配方为:澄粉38.19%、醋酸酯淀粉19.%、木薯淀粉41.81%、单甘酯0.1%、瓜尔豆胶1%.

  15. Guaifenesin has no effect on sputum volume or sputum properties in adolescents and adults with acute respiratory tract infections.

    Hoffer-Schaefer, Agathe; Rozycki, Henry J; Yopp, Melissa A; Rubin, Bruce K


    Guaifenesin (glyceryl guaiacolate ether [GGE]) has been studied as a cough suppressant and as an expectorant; however, published studies to date have failed to find a consistent benefit. An 8-day multi-center clinical trial was conducted to study the effect of two 600-mg extended-release GGE tablets twice daily for 1 week on cold symptoms, sputum volume, and properties in adolescents and adults with productive cough from an acute respiratory tract infection (RTI). The study enrolled 378 subjects (GGE, n = 188; and placebo, n = 190) who were otherwise healthy and had an RTI for up to 5 days before enrollment. Subjects suffered from at least 2 of 3 symptoms of cough, thickened mucus, and chest congestion. A total of 151 GGE and 144 control subjects completed the full protocol. Single-sputum samples were collected from each subject on days 1, 3, 4, and 8 of the study. The rheology and interfacial tension of sputum were measured, and 24-h collected samples from days 1 and 4 were analyzed for total volume and hydration. Symptoms in both the GGE and placebo groups improved to a similar degree over time. There were no significant differences between the GGE and placebo groups for sputum volume (P = .41), percent solids (P = .69), interfacial tension (P = .88), elasticity (P = .71), viscosity (P = .45), or mechanical impedance (P = .75). The recommended dose of GGE had no measurable effect on sputum volume or properties and is unlikely to be an expectorant or mucolytic when used to treat acute RTI. ( registration NCT01046136.).

  16. Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy.

    Kundu, Paromita; Mohanty, Chandana; Sahoo, Sanjeeb K


    Glioblastoma, the most aggressive form of brain and central nervous system tumours, is characterized by high rates proliferation, migration and invasion. The major road block in the delivery of drugs to the brain is the blood-brain barrier, along with the expression of various multi-drug resistance (MDR) proteins that cause the efflux of a wide range of chemotherapeutic drugs. Curcumin, a herbal drug, is known to inhibit cellular proliferation, migration and invasion and induce apoptosis of glioma cells. It also has the potential to modulate MDR in glioma cells. However, the greatest challenge in the administration of curcumin stems from its low bioavailability and high rate of metabolism. To circumvent the above pitfalls of curcumin we have developed curcumin-loaded glyceryl monooleate (GMO) nanoparticles (NP) coated with the surfactant Pluronic F-68 and vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for brain delivery. We demonstrated that our curcumin-loaded NPs inhibit cellular proliferation, migration and invasion along with a higher percentage of cell cycle arrest and telomerase inhibition, thus leading to a greater percentage apoptotic cell death in glioma cells compared with native curcumin. An in vivo study demonstrated enhanced bioavailability of curcumin in blood serum and brain tissue when delivered by curcumin-loaded GMO NPs compared with native curcumin in a rat model. Thus, curcumin-loaded GMO NPs can be used as an effective delivery system to overcome the challenges of drug delivery to the brain, providing a new approach to glioblastoma therapy. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Role Of S-Nitrosylation In The Extrinsic Apoptotic Signalling Pathway In Cancer

    Stéphanie Plenchette


    Full Text Available One of the key features of tumour cells is the acquisition of resistance to apoptosis. Thus, determining therapeutic strategies that circumvent apoptotic resistance and result in tumor regression is a challenge. One strategy to induce apoptosis is to activate death receptor signalling pathways. Members of the Tumor Necrosis Factor TNF-family death receptors ligand (TRAIL, FasL and TNF-α can originate from immune and non-immune cells. Death receptors, engaged by cognate ligands, can initiate multiple signaling pathways, which can generate diverse outcomes, including non-apoptosis-related signal. Knowledge on the molecular mechanisms (that determine death or survival of tumour cells following exposure to the TNF-family death receptors ligands have demonstrated that post-translational modifications of the signaling pathway components play a critical role in determining cell fate. Cell death can be sensed by nitric oxide (NO in a wide variety of tumour cells. S-nitrosylation, the covalent modification of a protein cysteine thiol by an NO moiety, has emerged as an important post-translational regulation for the TNF-family death receptor signaling pathways. It has been demonstrated that death receptor DR4 (TRAIL-R1 becomes S-nitrosylated and promotes apoptosis following a specific NO donor treatment (Tang et al., 2006. Then, our group has shown that S-nitrosylation of Fas, following glyceryl trinitrate (GTN exposure, promotes redistribution of the receptor to lipid rafts, formation of the death-inducing signal complex (DISC, and induction of cell death. Finally, I will discuss our recent efforts to decipher regulatory mechanism of the TNF-α/TNFR1 signalling cell death pathway by S-nitrosylation following GTN treatment.

  18. Sphincter-Preserving Therapy with Topical 2% Diltiazem for Chronic Anal Fissure: Our Experience

    Manish Swarnkar


    Full Text Available Background: Chronic anal fissure is a common problem across the world treated largely by surgical methods. Studies have demonstrated the efficacy of topical agents like Glyceryl Trinitrate (GTN in anal fissure but it has been shown to have side effects like headache and dizziness. There is a need for a pharmacological therapy for fissure which has fewer side effects. Hence, this study was taken up to assess the efficacy and adverse effects of topical 2% Diltiazem (DTZ gel. Aim & Objectives: To assess the efficacy and side effect of topical treatment with 2% DTZ gel in patient with chronic anal fissure. Material and Methods: Consecutive fifty adult patients with symptomatic chronic anal fissure attending the surgery clinic were enrolled in the study form February 2014- July 2014 and they were treated with regular topical application of 2% DTZ cream. Patients were followed up at regular intervals for symptomatic relief and healing of fissure. Results: In our study postdefecatory pain, bleeding and irritation were significantly reduced after 2week of therapy and a th primary healing rate of 86% (43 out of 50 at 6 week of therapy. The primary side-effects of 2% DTZ gel appeared to be perianal dermatitis and pruritis ani in 14% cases. Conclusion: Topical 2% DTZ gel is an effective agent in the treatment of chronic anal fissure. The need for hospital stay is abolished; psychological and financial burden on the patient is reduced. With a healing rate close to 90%, topical DTZ can be easily advised as the first line of treatment of chronic anal fissure.

  19. 下调PTEN基因对偏头痛大鼠三叉神经节CREB的调节作用%Down-Regulation of PTEN Induced The Modulation of CREB in Trigeminal Ganglia of Migraine Rats

    桂蓓; 申崇标; 陈力学; 周冀英; 谭戈


    本研究利用RNAi重组腺病毒(AdR-siPTEN)下调偏头痛大鼠三叉神经节的PTEN(phosphatase and tensin homolog deleted on chromosome ten)基因,探讨其对偏头痛大鼠行为学的影响,以及经Akt(serine-threonine kinase)信号途径对CREB(cAMP response element-binding protein)的调控情况.实验采用健康雄性SD大鼠,随机分为假手术组(Sham)、硝酸甘油模型组(GTN)、Ad-RFP非特异siRNA处理空载体对照组(Vehicle+GTN)、AdR-siPTEN下调组(AdR-siPTEN+GTN).用AdR-siPTEN重组腺病毒对大鼠进行预处理,然后通过硝酸甘油(glyceryl trinitrate,GTN)法建立大鼠偏头痛模型,进行大鼠挠头和爬笼次数的检测,并用RT-PCR和Western-blot法进行相关基因的mRNA和蛋白检测.结果表明,当PTEN基因表达下调时,有效缓解了偏头痛导致的挠头和爬笼行为,并激活Akt信号途径,增加其下游作用因子CREB的表达,进而可能经"PTEN/Akt/CREB"信号通路影响神经突触可塑性,参与了偏头痛的发病机制.

  20. Evidence that the nitrergic neurotransmitter and endothelium-derived relaxing factor might be S-nitrosothiols in the mouse corpus cavernosum.

    Büyükafşar K


    Full Text Available The effects of thimerosal, a sulfhydryl oxidizing agent on nitrergic, endothelium-dependent and -independent relaxations were investigated to examine the possibility that the nitrergic neurotransmitter and endothelium-derived relaxing factor (EDRF could be S-nitrosothiol or free nitric oxide (NO in the isolated mouse corpus cavernosum. Thimerosal (5 x 10(-6-2 x 10(-5 M inhibited or almost abolished electrical field stimulation--(EFS, 30V, 0.5 ms, 15 sec, 1, 2, 4, 8, 16 Hz, acetylcholine--(ACh, 5 x 10(-8-1.25 x 10(-6 M, glyceryl trinitrate--(GTN, 3 x 10(-7-3 x 10(-6 M, and S-nitrosoglutathione--(GSNO, 5 x 10(-6-1.25 x 10(-4 M induced relaxations. Thiomerosal inhibition seems to be specific to L-arginine NO pathways since it had no effect on acidified sodium nitrite--(10(-4-5 x 10(-4 M, photoactivated sodium nitrite--(2 x 10(-4 M, isoprenaline--(10(-6 M, or papaverine--(10(-4 M elicited relaxations. Moreover, the inhibitory effect of thimerosal on the nitrergic, ACh- or GTN-induced relaxations were partly reversed by sulfhydryl-containing compounds, L-cysteine (10(-3 M, dithiothreitol (10(-3 M, or glutathione (10(-3 M. However L-methionine (10(-3 M, which contains a methyl group on the sulphur atom, failed to restore the thimerosal inhibition. Thimerosal did not change the contraction produced by 10(-4 M NG-nitro-L-arginine methyl ester. These findings indicate that the nitrergic neurotransmitter as well as EDRF may not be free NO but NO-transferring molecules, probably S-nitrosothiols, in the mouse corpus cavernosum.

  1. Direct myocardial anti-ischaemic effect of GTN in both nitrate-tolerant and nontolerant rats: a cyclic GMP-independent activation of KATP.

    Csont, T; Szilvássy, Z; Fülöp, F; Nedeianu, S; Páli, T; Tosaki, A; Dux, L; Ferdinandy, P


    1. We have recently demonstrated that glyceryl trinitrate (GTN) exerts a direct myocardial anti-ischaemic effect in both GTN-tolerant and nontolerant rats. Here we examined if this effect is mediated by GTN-derived nitric oxide (NO) and involves guanosine 3'5' cyclic monophosphate (cyclic GMP) and ATP-sensitive K+ channels (KATP). 2. Rats were treated with 100 mg kg-1 GTN or vehicle s.c. three times a day for 3 days to induce vascular GTN-tolerance or nontolerance. Isolated working hearts obtained from either GTN-tolerant or nontolerant rats were subjected to 10 min coronary occlusion in the presence of 10-7 M GTN or its solvent. 3. GTN improved myocardial function and reduced lactate dehydrogenase (LDH) release during coronary occlusion in both GTN-tolerant and nontolerant hearts. 4. Cardiac NO content significantly increased after GTN administration in both GTN-tolerant and nontolerant hearts as assessed by electron spin resonance. However, cardiac cyclic GMP content measured by radioimmunoassay was not changed by GTN administration. 5. When hearts from both GTN-tolerant and nontolerant rats were subjected to coronary occlusion in the presence of the KATP-blocker glibenclamide (10-7 M), the drug itself did not affect myocardial function and LDH release, however, it abolished the anti-ischaemic effect of GTN. 6. We conclude that GTN opens KATP via a cyclic GMP-independent mechanism, thereby leading to an anti-ischaemic effect in the heart in both GTN-tolerant and nontolerant rats.

  2. Chronic anal fissure: new approaches to chemical sphincterotomy

    Mohammad hassan Emami


    Full Text Available

    • An anal fissure is a split in the mucosa extending from the anal verge towards the dentate line. It currently affects 10% of patients attending proctology clinics. Recent studies have highlighted the role of increased internal anal sphincter pressure and decreased anodermal blood flow in the pathogenesis of chronic anal fissures. Acute fissures usually heal with conservative management. Fissures lasting greater than two months with features of chronicity, are unlikely to heal with conservative management. Lateral internal sphincterotomy has been the treatment of choice for chronic anal fissures. Because of the disability associated with surgery for healing anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Among different chemical agents, Glyceryl trinitrate (GTN has been shown to be the first line treatment for chronic anal fissure but the transient sphincteric relaxation effect of pharmacologic agents such as GTN, makes them less effective than surgery. Although we have different forms of GTN products, they do not show a long acting effect on relaxing and enhancing the perfusion of anal sphincter, because they are soon metabolized. Most difficulties with current usage of drugs are due to poor compliance of patients. It can be taken into consideration that new formulation and novel combination of GTN with other treatments, in slow releasing forms may lead to acceptable strategies in the management of chronic anal fissure. As authors’ experience in this field, other clinical trials on the drug combination and slow releasing formulations are warranted to generate new data on the subject.
    • Key word: chronic anal fissure, review, chemical sphincterotomy 

  3. Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis

    Brissette Catherine A


    Full Text Available Abstract Background We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. Methods In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16. Acetate supplementation was induced using glyceryl triacetate (6g/kg by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. Results We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. Conclusions These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.

  4. Hydrocarbon charge of a bacterial gas field by prolonged methanogenesis: an example from the East Java Sea, Indonesia

    Noble, R.A.; Henk, F.H. [Atlantic Richfield Indonesia Inc., Jakarta (Indonesia)


    The Terang-Sirasun Field in the East Java Sea of Indonesia contains 1.0 trillion cubic feet (TCF) of dry gas reserves, which are made up of over 99.5% methane with {delta}{sup 13}C of -65 per thousandth and {delta}D of -185%. The methane was formed exclusively by methanogenic bacteria via the CO{sub 2} reduction pathway. The primary source sediments for the methane were identified based on bulk geochemical and absolute biomarker concentrations. Specifically, the C{sub 25} acyclic isoprenoid 2,6,10,15,19-pentamethyleicosane (PME), and related isoprenyl glyceryl ethers, which are well known markers for methanogenic archaebacteria, were used as indicators for sediment layers thought to have had the most abundant methanogen activity. Burial history analysis and precise biostratigraphic age control provided the framework for assessing the timing of hydrocarbon fill. Our findings show that methanogenic activity was highest in marine shelfal claystones (mid-outer neritic) ranging in age from 8 Ma (Late Miocene) to present. The gas is reservoired in limestones and sands of the Paciran Member, which are dated from 6.5 to 1.3 Ma (Late Miocene-Pliocene). The top seal for the present accumulation was deposited less than 0.5 Ma ago (Quarternary), although there is strong geological evidence that older seals existed. The information obtained from this field study provides evidence that large accumulations of bacterial methane do not necessarily require early entrapment of methane from freshly deposited marine sediments. Traps may be filled with bacterial gas long after the deposition of source beds, provided that the required conditions for active methanogenesis are maintained throughout this period. (author)

  5. The efficacy of Isotretinoin-loaded solid lipid nanoparticles in comparison to Isotrex® on acne treatment

    Shiva Golmohammadzadeh


    Full Text Available Abstract: Topical retinoids are considered as the first line therapy in the treatment of acne vulgaris, but they are associated with cutaneous irritation. In this study, isotretinoin-loaded solid lipid nanoparticles(IT-SLN were prepared to treat the mild to moderate acne. Also using IT-SLN would minimize IT adverse effects in comparison to commercial product, Isotrex®. This study was conducted to prepare and characterize IT-SLN and assessing the efficiency of IT-SLN comparing to Isotrex® acne. IT-SLN was prepared using hot high pressure homogenization method.  IT-SLN contained 0.05% IT in 5% of lipid phase (Glyceryl monostearate- GMS and tween 80 (2.5 % w/v was used as surfactant in the aqueous phase. IT-SLN was characterized by particle size analyzing, differential scanning calorimetry and transmission electron microscopy. Encapsulation efficacy was also obtained using spectrophotometry. The efficacy of IT-SLN was evaluated in a randomized, single-blind, parallel-group study and compared with Isotrex®. Forty patients encountered in the study and divided in two groups. Treatment regimen was once-nightly topical administration accompanied with topical administration of clindamycin 2% solution twice a day for 8 weeks. The particle size of IT-SLN was around 60 nm with PDI of 0.4 and zeta potential was about -40 mV. Encapsulation efficacy of IT in SLN in crystalline form was 84±0.21%. IT-SLN produced significantly better treatment than Isotrex® in both non-inflammatory and inflammatory lesions according to its recovery percent after 8 weeks. Also IT-SLN gained better global assessment scores. Our results showed that IT-SLN had higher efficacy than Isotrex® to clear non-inflammatory and inflammatory lesions.

  6. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.

    Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Fortner, Karen A; Viapiano, Mariano S; Jaworski, Diane M


    Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth.

  7. Exploring the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading.

    Shi, Chenjun; Sun, Yujiao; Wu, Haiyang; Zhu, Chengyun; Wei, Guoguang; Li, Jinfeng; Chan, Tenglan; Ouyang, Defang; Mao, Shirui


    The objective of this paper is to explore the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading, and elucidate whether drug-polymer compatibility, as predicted by Hansen solubility parameters (HSPs), can be used as a tool for drug-polymer pairs screening and guide the design of grafted polymeric micelles. HSPs of 27 drugs and three grafted copolymers were calculated according to group contribution method. The drug-polymer compatibilities were evaluated using the approaches of Flory-Huggins interaction parameters (χFH) and polarity difference (△Xp). Two models, model A and B, were put forward for drug-polymer compatibility prediction. In model A, hydrophilic/hydrophobic part as a whole was regarded as one segment. And, in model B, hydrophilic and hydrophobic segments were evaluated individually. First of all, using chitosan (CS)-grafted-glyceryl monooeate (GMO) based micelle as an example, the suitability of model A and model B for predicating drug-polymer compatibility was evaluated theoretically. Thereafter, corresponding experiments were carried out to check the validity of the theoretical prediction. It was demonstrated that Model B, which evaluates drug compatibility with both hydrophilic and hydrophobic segments of the copolymer, is more reliable for drug-polymer compatibility prediction. Moreover, the approach of model B allows for the selection of a defined grafted polymer with for a specific drug and vice versa. Thus, drug compatibility evaluation via HSPs with both hydrophilic and hydrophobic segments is a suitable tool for the rational design of grafted polymeric micelles. The molecular dynamics (MD) simulation study provided further support to the established model and experimental results.

  8. Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - updated June 2014.

    Dumonceau, Jean-Marc; Andriulli, Angelo; Elmunzer, B Joseph; Mariani, Alberto; Meister, Tobias; Deviere, Jacques; Marek, Tomasz; Baron, Todd H; Hassan, Cesare; Testoni, Pier A; Kapral, Christine


    This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the prophylaxis of post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis. Main recommendations 1 ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP in all patients without contraindication. In addition to this, in the case of high risk for post-ERCP pancreatitis (PEP), the placement of a 5-Fr prophylactic pancreatic stent should be strongly considered. Sublingually administered glyceryl trinitrate or 250 µg somatostatin given in bolus injection might be considered as an option in high risk cases if nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated and if prophylactic pancreatic stenting is not possible or successful. 2 ESGE recommends keeping the number of cannulation attempts as low as possible. 3 ESGE suggests restricting the use of a pancreatic guidewire as a backup technique for biliary cannulation to cases with repeated inadvertent cannulation of the pancreatic duct; if this method is used, deep biliary cannulation should be attempted using a guidewire rather than the contrast-assisted method and a prophylactic pancreatic stent should be placed. 4 ESGE suggests that needle-knife fistulotomy should be the preferred precut technique in patients with a bile duct dilated down to the papilla. Conventional precut and transpancreatic sphincterotomy present similar success and complication rates; if conventional precut is selected and pancreatic cannulation is easily obtained, ESGE suggests attempting to place a small-diameter (3-Fr or 5-Fr) pancreatic stent to guide the cut and leaving the pancreatic stent in place at the end of ERCP for a minimum of 12 - 24 hours. 4 ESGE does not recommend endoscopic papillary balloon dilation as an alternative to sphincterotomy in routine ERCP, but it may be advantageous in selected patients; if this

  9. Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets.

    Fukuda, Mamoru; Goto, Akinori


    A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax® was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.

  10. Effect of formulation composition on the properties of controlled release tablets prepared by roller compaction.

    Hariharan, Madhusudan; Wowchuk, Christina; Nkansah, Paul; Gupta, Vishal K


    This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled-release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t70 values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t70 data and gave an adjusted r-square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and

  11. Competition and allostery govern substrate selectivity of cyclooxygenase-2

    Mitchener, Michelle M.; Hermanson, Daniel J.; Shockley, Erin M.; Brown, H. Alex; Lindsley, Craig W.; Reese, Jeff; Rouzer, Carol A.; Lopez, Carlos F.; Marnett, Lawrence J.


    Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and its ester analog, 2-arachidonoylglycerol (2-AG), to prostaglandins (PGs) and prostaglandin glyceryl esters (PG-Gs), respectively. Although the efficiency of oxygenation of these substrates by COX-2 in vitro is similar, cellular biosynthesis of PGs far exceeds that of PG-Gs. Evidence that the COX enzymes are functional heterodimers suggests that competitive interaction of AA and 2-AG at the allosteric site of COX-2 might result in differential regulation of the oxygenation of the two substrates when both are present. Modulation of AA levels in RAW264.7 macrophages uncovered an inverse correlation between cellular AA levels and PG-G biosynthesis. In vitro kinetic analysis using purified protein demonstrated that the inhibition of 2-AG oxygenation by high concentrations of AA far exceeded the inhibition of AA oxygenation by high concentrations of 2-AG. An unbiased systems-based mechanistic model of the kinetic data revealed that binding of AA or 2-AG at the allosteric site of COX-2 results in a decreased catalytic efficiency of the enzyme toward 2-AG, whereas 2-AG binding at the allosteric site increases COX-2’s efficiency toward AA. The results suggest that substrates interact with COX-2 via multiple potential complexes involving binding to both the catalytic and allosteric sites. Competition between AA and 2-AG for these sites, combined with differential allosteric modulation, gives rise to a complex interplay between the substrates, leading to preferential oxygenation of AA. PMID:26392530

  12. Controlled release implants based on cast lipid blends.

    Kreye, F; Siepmann, F; Zimmer, A; Willart, J F; Descamps, M; Siepmann, J


    The aim of this study was to use lipid:lipid blends as matrix formers in controlled release implants. The systems were prepared by melting and casting and thoroughly characterized before and after exposure to the release medium. Based on the experimental results, a mechanistic realistic mathematical model was used to get further insight into the underlying drug release mechanisms. Importantly, broad spectra of drug release patterns could be obtained by simply varying the lipid:lipid blend ratio in implants based on Precirol ATO 5 (glyceryl palmitostearate):Dynasan 120 (hardened soybean oil) mixtures loaded with propranolol hydrochloride. Release periods ranging from a few days up to several months could be provided. Interestingly, the drug release rate monotonically decreased with increasing Dynasan 120 content, except for implants containing about 20-25% Precirol, which exhibited surprisingly high release rates. This could be attributed to the incomplete miscibility of the two lipids at these blend ratios: DSC thermograms showed phase separation in these systems. This is likely to cause differences in the implants' microstructure, which determines the mobility of water and dissolved drug as well as the mechanical stability of the systems. Purely diffusion controlled drug release was only observed at Precirol ATO 5 contents around 5-10%. In all other cases, limited drug solubility effects or matrix former erosion are also expected to play a major role. Thus, lipid:lipid blends are very interesting matrix formers in controlled release implants. However, care must be taken with respect to the mutual miscibility of the compounds: in case of phase separation, surprisingly high drug release rates might be observed.

  13. Determination of 26 kinds of residual solvent in cigarette paper by headspace gas chromatography mass spectrometry%顶空-气相色谱质谱联用法分析烟用纸张中26种溶剂残留物

    杜显生; 张颖明; 侯鑫


    建立了烟用纸张中26种溶剂残留物的顶空—气相色谱质谱联用(HS-GCMS)研究方法。以三醋酸甘油酯作为溶剂,使用静态顶空仪对烟用纸张进行前处理,溶剂残留混合组分导入气相色谱仪中逐一分离,进入质谱检测器进行定性定量分析。结果表明:方法的回收率在87.1%~107.8%之间,检出限在0.001~0.204m g/m2之间,相对标准偏差(R S D)小于5%。该方法可同时检测烟用纸张中26种溶剂残留物。%A determination method of 26 kinds of solvent residual in cigarette paper by headspace gas chromatography mass spectrometry (HS-GCMS) was established. Cigarette paper sample was pretreated with static headspace sampling used glyceryl triacetate as dissolvent. The mixed solvent residues were separated speciifcally by gas chromatography mass spectrometry and were qualitatively and quantitatively analyzed in MS Detector. The results showed that this method has good relative standard deviation (RSD<5%). Recovery rate is 87.1% to 107.8% and the detection limit is 0.001 to 0.204mg/m2. So this testing method can be applied to determine 26 kinds residual solvent in cigarette paper simultaneously.

  14. Biodegradation and toxicity of vegetable oils in contaminated aquatic environments: Effect of antioxidants and oil composition.

    Salam, Darine A; Suidan, Makram T; Venosa, Albert D


    Antioxidants may affect the oxidative rate of vegetable oils determining their fate and impact in contaminated aquatic media. In previous studies, we demonstrated the effectiveness of butylated hydroxytoluene (BHT), one of the most used antioxidants in edible oils, in enhancing the biodegradation of glyceryl trilinoleate, a pure triacylglycerol of cis,cis-9,12-octadecadienoic acid (C18:2 delta), through retarding its oxidative polymerization relatively to the oil with no added antioxidant. In this study, the effect of BHT on the biodegradation and toxicity of purified canola oil, a mixed-acid triacylglycerol with high C18:1 content, was investigated in respirometric microcosms and by use of the Microtox® assay. Investigations were carried out in the absence and presence (200 mg kg(-1)) of the antioxidant, and at an oil loading of 0.31 L m(-2) (333 gal acre(-1)). Substantial oil mineralization was achieved after 16 weeks of incubation (>77%) and was not significantly different (p>0.05) between the two BHT treatments, demonstrating an important role of the oil fatty acid composition in determining the potency of antioxidants and, consequently, the fate of spilled vegetable oils. Furthermore, for both treatments, toxicity was measured at early stages of the experiments and disappeared at a later stage of incubation. The observed transient toxicity was associated with the combined effect of toxic biodegradation intermediates and autoxidation products. These results were supported by the gradual disappearance of BHT in the microcosms initially supplemented with the antioxidant, reaching negligible amounts after only 2 weeks of incubation. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Self-assembled nano-architecture liquid crystalline particles as a promising carrier for progesterone transdermal delivery.

    Elgindy, Nazik A; Mehanna, Mohammed M; Mohyeldin, Salma M


    The study aims to elaborate novel self-assembled liquid crystalline nanoparticles (LCNPs) for management of hormonal disturbances following non-invasive progesterone transdermal delivery. Fabrication and optimization of progesteroneloaded LCNPs for transdermal delivery were assessed via a quality by design approach based on 2(3) full factorial design. The design includes the functional relationships between independent processing variables and dependent responses of particle size, polydispersity index, zeta potential, cumulative drug released after 24h and ex-vivo transdermal steady flux. The developed nanocarrier was subjected to TEM (transmission electron microscope) for morphological elucidation and stability study within a period of three months at different storage temperatures. The cubic phase of LCNPs was successfully prepared using glyceryl monooleate (GMO) via the emulsification technique. Based on the factorial design, the independent operating variables significantly affected the five dependent responses. The cubosomes hydrodynamic diameters were in the nanometric range (101-386 nm) with narrow particle size distribution, high negative zeta potential ≥-30 mV and entrapment efficiency ≥94%. The LCNPs succeeded in sustaining progesterone release for almost 24h, following a non-fickian transport of drug diffusion mechanism. Ex-vivo study revealed a significant enhancement up to 6 folds in the transdermal permeation of progesterone-loaded LCNPs compared to its aqueous suspension. The optimized LCNPs exhibited a high physical stability while retaining the cubic structure for at least three months. Quality by design approach successfully accomplished a predictable mathematical model permitting the development of novel LCNPs for transdermal delivery of progesterone with the benefit of reducing its oral route side effects.

  16. Langmuir and Langmuir-Blodgett films of multifunctional, amphiphilic polyethers with cholesterol moieties.

    Reuter, Sascha; Hofmann, Anna M; Busse, Karsten; Frey, Holger; Kressler, Jörg


    Langmuir films of multifunctional, hydrophilic polyethers containing a hydrophobic cholesterol group (Ch) were studied by surface pressure-mean molecular area (π-mmA) measurements and Brewster angle microscopy (BAM). The polyethers were either homopolymers or diblock copolymers of linear poly(glycerol) (lPG), linear poly(glyceryl glycidyl ether) (lPGG), linear poly(ethylene glycol) (lPEG), or hyperbranched poly(glycerol) (hbPG). Surface pressure measurements revealed that the homopolymers lPG and hbPG did not stay at the water surface after spreading and solvent evaporation, in contrast to lPEG. Because of the incorporation of the Ch group in the polymer structure, stable Langmuir films were formed by Ch-lPG(n), Ch-lPGG(n), and Ch-hbPG(n). The Ch-hbPG(n), Ch-lPEG(n), Ch-lPEG(n)-b-lPG(m), Ch-lPEG(n)-b-lPGG(m), and Ch-lPEG(n)-b-hbPG(m) systems showed an extended plateau region assigned to a phase transition involving the Ch groups. Typical hierarchically ordered morphologies of the LB films on hydrophilic substrates were observed for all Ch-initiated polymers. All LB films showed that Ch of the Ch-initiated homopolymers is able to crystallize. This strong tendency of self-aggregation then triggers further dewetting effects of the respective polyether entities. Fingerlike morphologies are observed for Ch-lPEG(69), since the lPEG(69) entity is able to undergo crystallization after transfer onto the silicon substrate.

  17. 红谷牛奶的研制%Preparation of a Red Rice Milk

    熊贤富; 黄红岑; 蔡水根


    A compound protein beverage was prepared by red bean, red rice powder, whole milk powder and peanut butte Orthogonal experiment showed that the prepared sample had the best sensory quality when it contained 3.0% whole milk powder, 3.0% red bean, 1.0% red rice powder, 1.0% peanut butter and 7.5% sugar. The stability of the product was investigated by the insulation test. The result indicated that the best formula of emulsion stabilizer was: 0.15% emulsion (50% glyceryl monostearate and 50% sugar ester), 0.05% gellan gum, 0.12% xanthan gum, 0.03% &-carrageenan, with which the product showed good sensory quality and high stability.%以红豆、红米粉、全脂奶粉、花生酱等为主要原料制作一种复合蛋白饮料红谷牛奶,通过正交试验确定最佳感官配方为:3.0%全脂奶粉、3.0%红豆、1.0%红米粉、1.0%花生浆和7.5%白砂糖.通过对产品进行保温试验研究,得出最佳的乳化稳定剂的配方为:0.15%乳化剂(50%单甘酯和50%蔗糖脂肪酸酯)和0.05%结冷胶、0.12%黄原胶、0.03%的k-卡拉胶,此条件下能获得较好的感官品质和稳定性.

  18. Antifungal activity of Zataria multiflora essential oil-loaded solid lipid nanoparticles in-vitro condition

    Mahboobeh Nasseri


    Full Text Available Objective(s: The aim of the present study was to prepare, characterize, and evaluate solid lipid nanoparticles (SLNs containing Zataria multiflora essential oil (ZEO. Materials and Methods: In this study, Z. multiflora essential oil-loaded solid lipid nanoparticles (ZE-SLNs were prepared to improve its efficiency in controlling some fungal pathogens. SLNs containing Z. multiflora essential oil were prepared by high shear homogenization and ultra sound technique. ZEO-SLNs contained 0.03% ZEO in 5% of lipid phase (Glyceryl monostearate-GMS and Precirol® ATO 5.Tween 80 and Poloxamer 188 (2.5% w/v were used as surfactant in the aqueous phase. The antifungal efficacy of ZE-SLNs and ZEO was compared under in vitro conditions. Results:The particle size of ZE-SLNs was around 255.5±3 nm with PDI of 0.369±0.05 and zeta potential was about -37.8±0.8 mV. Encapsulation efficacy of ZE-SLNs in crystalline form was 84±0.92%. The results showed that the ZEO and ZE-SLNs had 54 and 79% inhibition on the growth of fungal pathogens, respectively. The minimum inhibitory concentration (MIC under in vitro conditions for the ZEO on the fungal pathogens of Aspergillus ochraceus, Aspergillus niger, Aspergillus flavus, Alternaria solani, Rhizoctonia solani, and Rhizopus stolonifer was 300, 200, 300, 200, 200 and 200 ppm, respectively, for ZE-SLNs, it was 200, 200, 200, 100, 50 and 50 ppm. The antifungal efficacy of ZE-SLNs was significantly more than ZEO. Conclusion: Our results showed that the SLNs were suitable carriers for Z. multiflora essential oil in controlling the fungal pathogens and merits further investigation.

  19. Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.

    Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A


    Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.

  20. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells.

    Barsoum, Ivraym B; Smallwood, Chelsea A; Siemens, D Robert; Graham, Charles H


    Immune escape is a fundamental trait of cancer in which mechanistic knowledge is incomplete. Here, we describe a novel mechanism by which hypoxia contributes to tumoral immune escape from cytotoxic T lymphocytes (CTL). Exposure of human or murine cancer cells to hypoxia for 24 hours led to upregulation of the immune inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1), in a manner dependent on the transcription factor hypoxia-inducible factor-1α (HIF-1α). In vivo studies also demonstrated cellular colocalization of HIF-1α and PD-L1 in tumors. Hypoxia-induced expression of PD-L1 in cancer cells increased their resistance to CTL-mediated lysis. Using glyceryl trinitrate (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1α accumulation in hypoxic cells, we prevented hypoxia-induced PD-L1 expression and diminished resistance to CTL-mediated lysis. Moreover, transdermal administration of GTN attenuated tumor growth in mice. We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells. This increase in apoptosis was prevented by blocking the interaction of PD-L1 with PD-1, the PD-L1 receptor on T cells, or by addition of GTN. Our findings point to a role for hypoxia/HIF-1 in driving immune escape from CTL, and they suggest a novel cancer immunotherapy to block PD-L1 expression in hypoxic-tumor cells by administering NO mimetics.

  1. A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

    Wiltshire, Esko J; Peña, Alexia S; MacKenzie, Karen; Bose-Sundernathan, Tulika; Gent, Roger; Couper, Jennifer J


    To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Investigation of paramedics' compliance with clinical practice guidelines for the management of chest pain.

    Figgis, Ken


    BACKGROUND: Acute coronary syndromes remain a leading cause of preventable early deaths. However, previous studies have indicated that paramedics\\' compliance with chest pain protocols is suboptimal and that many patients do not receive the benefits of appropriate prehospital treatment. AIMS: To evaluate paramedics\\' level of compliance with national clinical practice guidelines and to investigate why, in certain circumstances, they may deviate from the clinical guidelines. SETTING: The Health Service Executive Mid-Western Regional Ambulance Service which serves a mixed urban and rural population across three counties in the west of Ireland. METHOD: A retrospective review of completed ambulance Patient Care Report Forms was conducted for all adult patients with non-traumatic chest pain treated between 1 December 2007 and 31 March 2008. During the same study period, paramedics were asked to complete a prospective questionnaire survey investigating the rationale behind their treatment decisions, their estimation of patient risk and their attitudes towards the clinical practice guidelines and training. RESULTS: 382 completed Patient Care Report Forms were identified for patients with chest pain, of whom 84.8% received ECG monitoring, 75.9% were given oxygen, 44.8% were treated with sublingual glyceryl trinitrate (GTN) and 50.8% were treated with aspirin. Only 20.4% of patients had a prehospital 12-lead ECG recorded. 58 completed questionnaires were returned (response rate 15%); 64% of respondents said they had received insufficient training to identify ECG abnormalities. CONCLUSIONS: Prehospital treatment with oxygen, aspirin, sublingual GTN and ECG monitoring remains underused by paramedics, even though only a small number of patients had documented contraindications to their use. The small number of patients who received a prehospital 12-lead ECG is a cause of particular concern and suggests that incomplete patient assessment may contribute to undertreatment

  3. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration.

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Boyd, Ben J


    This study is the first to demonstrate the ability of nanostructured liquid crystal particles to sustain the absorption of a poorly water soluble drug after oral administration. Cubic (V(2)) liquid crystalline nanostructured particles (cubosomes) formed from phytantriol (PHY) were shown to sustain the absorption of cinnarizine (CZ) beyond 48h after oral administration to rats. Plasma concentrations were sustained within the range of 21.5±1.5ng/mL from 12 to 48h. In stark contrast, cubosomes prepared using glyceryl monooleate (GMO) did not sustain the absorption of CZ and drug concentrations fell below quantifiable levels after 24h. Sustained absorption of CZ from PHY cubosomes lead to a significant enhancement (pnanostructured particles in simulated gastric and intestinal fluids using small angle x-ray scattering (SAXS) revealed that the V(2)Pn3m nanostructure of PHY cubosomes was maintained for extended periods of time, in contrast to GMO cubosomes where the V(2)Im3m nanostructure was lost within 18h after exposure, suggesting that degradation of the LC nanostructure may limit sustained drug release. In addition, PHY cubosomes were shown to be extensively retained in the stomach (>24h) leading to the conclusion that in the case of non-digestible PHY cubosomes, the stomach may act as a non-sink reservoir that facilitates the slow release of poorly water soluble drugs, highlighting the potential use of non-digestible LC nanostructured particles as novel sustained oral drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Coexisting typical migraine in familial hemiplegic migraine.

    Hansen, Jakob Møller; Thomsen, Lise Lykke; Olesen, Jes; Ashina, Messoud


    In contrast to patients with migraine with aura (MA) and migraine without aura (MO), most patients with familial hemiplegic migraine (FHM) do not report migraine-like attacks after pharmacologic provocation with glyceryl trinitrate (GTN), a donor of nitric oxide. In the present study, we examined patients with FHM without known gene mutations and hypothesized that 1) GTN would cause more migraine-like attacks in patients with FHM compared to controls, and 2) GTN would cause more migraine attacks in patients with FHM with coexisting MA or MO compared to the pure FHM phenotype. The study design was a balanced provocation study. Twenty-three patients with FHM and 11 healthy controls received a continuous IV infusion of 0.5 mug/kg/min GTN over 20 minutes. We found no difference in the incidence of migraine-like attacks comparing all patients with FHM (30%) to controls (9%) (p = 0.15). Patients with FHM with coexisting MA or MO reported more migraine attacks after GTN (55%) than patients with the pure FHM phenotype (8.3%) (p = 0.02). Compared to healthy controls, more patients with FHM with coexisting MA or MO reported migraine-like attacks than controls (p = 0.03), whereas the FHM group with the pure FHM phenotype did not (p > 0.05). Compared to patients with migraine with aura (MA) and migraine without aura (MO), patients with familial hemiplegic migraine (FHM) without known gene mutations display a reduced sensitivity to nitric oxide. A subset of patients with FHM with coexisting nonhemiplegic migraine is more sensitive than controls. These data extend our previous findings that pathophysiologic pathways in FHM may differ from those of MO and MA.

  5. 高级脂肪醇类消泡剂主单体的合成及应用%Preparation and application of the main monomer for high fatty alcohol defoamer

    于正浪; 郭睿; 季振青; 贾建民


    以基团保护法合成了硬脂酸单甘油酯;通过正交实验研究获得了优化的合成条件:带水剂用量为120(mL/molGT),催化剂用量为5%,甘油与丙酮和硬脂酸的摩尔比为1:1.5:0.7.产物经IR和元素分析表征,确定产物为目的产物.合成的产物与混合高级脂肪醇复配研制出水基乳液非硅消泡剂,通过测定其技术指标及与国内外产品进行比较发现自制消泡剂适用于抄纸和涂布工序中,且性能优异.%Glyceryl monostearate was synthesized by a method of group protection. The optimum conditions for the synthesis were found through orthogonal experiments as: petroleum ether is 120 (mL/molGT), the molar ratio of glycerol I acetone : stearic acid is 1 :5 : 0.7, the mass of catalyst is 5% of glycerol. The elemental analysis and IR spectrogram of the product were identical with the target product. Then the product was mixed with high-level fatty alcohol so as to develop a water-based emulsion non-silicon defoamer. A comparative study on the technical specifications showed that this defoamer is suitable for papermaking and coating process.

  6. Ambulatory blood pressure monitoring and endothelium-dependent vasodilation in the elderly athletes.

    Galetta, F; Franzoni, F; Plantinga, Y; Ghiadoni, L; Rossi, M; Prattichizzo, F; Carpi, A; Taddei, S; Santoro, G


    Regular exercise is a key component of cardiovascular risk prevention strategies, because it is associated with a variety of beneficial metabolic and vascular effects that reduce mortality and the incidence of cardiovascular adverse events. Endothelium plays an important role in the local regulation of vascular tone and structure, mainly by nitric oxide (NO) synthesis and action. Aim of the present study was to evaluate in elderly athletes the effect of regular aerobic exercise on arterial blood pressure (BP) and on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery. The study population included 30 male subjects (mean age 65.6+/-5.6 years), who had practiced endurance running at a competitive level for at least 40 years, and 28 age- and sex-matched subjects (mean age 64.5+/-4.5 years) with sedentary lifestyle and free of cardiovascular disease. Athletes and control subjects underwent standard 12-lead ECG, clinic BP, 24-h ambulatory BP monitoring and endothelium-dependent FMD and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, in the brachial artery by high-resolution ultrasonography. Systolic clinic and ambulatory 24-h BP were significantly lower in the athletes, than in the controls (Pathletes (Pathletes also had a lower 24-h, day-time and night-time heart rate (HR) (Pathletes (Pathletes showed higher FMD than elderly sedentary subjects (Pphysical activity can counteract the age-related endothelial dysfunction that characterizes sedentary aging, preserving the capacity of the endothelium-dependent vasodilation and reduces BP values improving arterial pressure control.

  7. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  8. Carrier-mediated ion transport in lipid bilayer membranes.

    Laprade, R; Grenier, F; Pagé-Dansereau, M; Dansereau, J


    The electrical properties predicted by a widely accepted model for carrier-mediated ion transport in lipid bilayers are described. The different steps leading to ion transport and their associated rate constants are reaction at the interface between an ion in the aqueous phase and a carrier in the membrane (kRi), followed by translocation of the ion-carrier complex across the membrane interior (kis) and its dissociation at the other interface (kDi) after which the free carrier crosses back the membrane interior (ks). Results on glyceryl monooleate (GMO) membranes for a family of homologue carriers, the macrotetralide actin antibiotics (nonactin, monactin, dinactin, trinactin, and tetranactin) and a variety of ions (Na+, Cs+, Rb+, K+, NH4+, and Tl+) are presented. Internally consistent data obtained from steady-state electrical measurements (zero-current potential and conductance, current-voltage relationship) allow us to obtain the equilibrium permeability ratios for the different ions and show that for a given carrier kRi is relatively invariant from one ion to the other, except for Tl+ (larger), which implies that the ionic selectivity is controlled by the dissociation of the complex. The values of the individual rate constants obtained from current relaxation experiments are also presented and confirm the findings from steady-state measurements, as well as the isostericity concept for complexes of different ions with the same carrier (kis invariant). These also allow us to determine the aqueous phase membrane and torus membrane partition coefficients. Finally, the observed increase in kis from nonactin to tetranactin and, for all homologues, from GMO-decane to solvent-free GMO membranes, together with the concomitant decrease in kDi, can be explained in terms of modifications of electrostatic energy profiles induced by variations in carrier size and membrane thickness.

  9. Characterization of oil-free and oil-loaded liquid-crystalline particles stabilized by negatively charged stabilizer citrem.

    Nilsson, Christa; Edwards, Katarina; Eriksson, Jonny; Larsen, Susan Weng; Østergaard, Jesper; Larsen, Claus; Urtti, Arto; Yaghmur, Anan


    The present study was designed to evaluate the effect of the negatively charged food-grade emulsifier citrem on the internal nanostructures of oil-free and oil-loaded aqueous dispersions of phytantriol (PHYT) and glyceryl monooleate (GMO). To our knowledge, this is the first report in the literature on the utilization of this charged stabilizing agent in the formation of aqueous dispersions consisting of well-ordered interiors (either inverted-type hexagonal (H(2)) phases or inverted-type microemulsion systems). Synchrotron small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were used to characterize the dispersed and the corresponding nondispersed phases of inverted-type nonlamellar liquid-crystalline phases and microemulsions. The results suggest a transition between different internal nanostructures of the aqueous dispersions after the addition of the stabilizer. In addition to the main function of citrem as a stabilizer that adheres to the surface of the dispersed particles, it has a significant impact on the internal nanostructures, which is governed by the following factors: (1) its penetration between the hydrophobic tails of the lipid molecules and (2) its degree of incorporation into the lipid-water interfacial area. In the presence of citrem, the formation of aqueous dispersions with functionalized hydrophilic domains by the enlargement of the hydrophilic nanochannels of the internal H(2) phase in hexosomes and the hydrophilic core of the L(2) phase in emulsified microemulsions (EMEs) could be particularly attractive for solubilizing and controlling the release of positively charged drugs.

  10. Disposition and association of the steric stabilizer Pluronic® F127 in lyotropic liquid crystalline nanostructured particle dispersions.

    Tilley, Adam J; Drummond, Calum J; Boyd, Ben J


    Liquid crystalline nanostructured particles, such as cubosomes and hexosomes, are most often colloidally stabilised using the tri-block co-polymer Pluronic® F127. Although the effect of F127 on the internal particle nanostructure has been well studied, the associative aspects of F127 with cubosomes and hexosomes are poorly understood. In this study the quantitative association of F127 with phytantriol-based cubosomes and hexosomes was investigated. The amount of free F127 in the dispersions was determined using pressure ultra-filtration. The percentage of F127 associated with the particles plateaued with increasing F127 concentration above the critical aggregation concentration. Hence the free concentration of F127 in the dispersion medium was proposed as a key factor governing association below the CMC, and partitioning of F127 between micelles and particles occurred above the CMC. The association of F127 with the particles was irreversible on dilution. The F127 associated with both the external and internal surfaces of the phytantriol cubosomes. The effects of lipid and F127 concentration, lipid type, dilution of the dispersions and internal nanostructure were also elucidated. A greater amount of F127 was associated with cubosomes comprised of glyceryl monooleate (GMO) than those prepared using phytantriol. Hexosomes prepared using a mixture of phytantriol and vitamin E acetate (vitEA) had a greater amount of F127 associated with them than phytantriol cubosomes. Hexosomes prepared using selachyl alcohol had less F127 associated with them than phytantriol:vitEA-based hexosomes and GMO-based cubosomes. This indicated that both the lipid from which the particles are composed and the particle internal nanostructure have an influence on the association of F127 with lyotropic liquid crystalline nanostructured particles. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Relaxant mechanisms of 3, 5, 7, 3', 4'-pentamethoxyflavone on isolated human cavernosum.

    Jansakul, Chaweewan; Tachanaparuksa, Kuldej; Mulvany, Michael J; Sukpondma, Youwapa


    We have investigated effects and mechanisms responsible for the activity of 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on isolated human cavernosum. PMF is the major flavone isolated from Kaempferia parviflora claimed to act as an aphrodisiac. PMF caused relaxation of phenylephrine precontracted human cavernosal strips, and this effect was slightly inhibited by N(G)-nitro-l-arginine, a nitric oxide synthase inhibitor, but not by ODQ (soluble guanylate cyclase inhibitor), TEA (tetraethylammonium, blocker of voltage-dependent K(+) channels) or glybenclamide (blocker of ATP-dependent K(+) channels). PMF did not significantly inhibit the relaxant activity of glyceryltrinitrate or acetylcholine on human cavernosal strips precontracted with phenylephrine. In contrast, sildenafil (phosphodiesterase inhibitor) potentiated the relaxant activity of glyceryl trinitrate but not of acetylcholine. In normal Krebs solution with nifedipine (blocker of l-type Ca(2+) channels), or in Ca(2+)-free Krebs solution, PMF caused a further inhibition of human cavernosum contracted with phenylephrine. In human cavernosum treated with thapsigargin (inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase) in Ca(2+)-free medium, PMF suppressed the concentration-response curve of human cavernosum to phenylephrine and a further suppression was found when SKF-96365 (a blocker of store-operated Ca(2+) channels and Y-27632 (inhibitor of Rho-kinase)), but not nifedipine, were added sequentially. Thus, PMF had only a weak effect on the release of nitric oxide, and had no effect as a K(ATP)- or K(Ca) channel opener, a phosphodiesterase inhibitor, a store-operated Ca(2+) channel blocker or a Rho-kinase inhibitor. Therefore, these studies suggest that PMF causes relaxation of human cavernosum through voltage-dependent Ca(2+) channels and other mechanisms associated with calcium mobilization. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3', 4'-pentamethoxyflavone to middle-aged male rats.

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan


    Effects of treatment of middle-aged male rats with 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on vascular and perivascular adipose tissue (PVAT) functions and blood chemistry were investigated. Rats received PMF (22 mg/kg), orally or vehicle, twice a day for 6 weeks. The PMF-treated rats had lower serum glucose, higher HDL-C levels, but no change in other parameters. Thoracic aortic and mesenteric rings of PMF treated rats produced lower maximal contraction to phenylephrine that was normalized by N(G)-nitro-L-arginine (L-NA) or endothelial removal. The aortic- and mesenteric rings of the PMF treated rats showed improved relaxation to acetylcholine, but not to glyceryl trinitrate, and had higher eNOS protein. DL-propargylglycine (PAG) caused greater increase in the baseline tension of the PMF-treated aortic ring and higher contraction to low concentrations of phenylephrine. PVAT lowered the contractile response of the L-NA pretreated aortic rings to phenylephrine for both groups, but PAG had no effect. The cystathionine-γ-lyase (CSE) protein of the thoracic rings, but not of the PVAT, shows increased expression after PMF treatment. Overall, PMF treatment of middle aged rats appeared to increase production of NO and H2S from the blood vessels by upregulating the expression of eNOS and CSE. PMF also decreased fasting serum glucose and increased HDL-C levels, with no toxicity to liver and kidney functions. Thus, PMF is a novel compound for possible use as a health product to prevent and/or to reduce the development of diabetes type II and/or cardiovascular disease.

  13. Studies on chemical constituents of Mongolian medicine Orobanche coerulescens%蒙药列当的化学成分研究

    邵红霞; 杨九艳; 鞠爱华


    目的:研究蒙药列当(Orobanche coerulescens Steph)的化学成分,为进一步明确其中的有效成分奠定基础.方法:利用普通硅胶柱色谱、大孔树脂柱色谱,Sephadex LH-20色谱技术及重结晶等方法进行分离、纯化,并利用波谱技术和理化性质确定了化合物的结构.结果:从中分离得到9个化合物,分别鉴定为:甘露醇①,β-谷甾醇②,豆甾醇③,二十烷酸-1-甘油酯④,β-胡萝卜苷⑤,琥珀酸⑥,Crenatoside⑦,麦角甾苷⑧,D-松醇⑨.结论:其中化合物③,④,⑦,⑧,⑨为首次从该植物中获得.%Objective: To study the chemical constituents of mongolian medicine Orobanche coerulescens Steph in order to clarify the effective constituents. Methods: The chemical constituents were purified by silica gel, porous resin, Sephadex LH-20 and recrysta Uization and then the structures were determined by spectralanalyses. Results: Nine compounds were obtained and determined as D-mannitol①β-sitosterol②, tigmasterol③, Glyceryl arachidate④, β-Daucosterol⑤, succinicacid⑥, Crenatosid ⑦, Acteoside⑧, D-pinitol⑨. Conclusion: Compounds ③, ④, ⑦, ⑧, ⑨ were obtained from this plant for the first time.

  14. Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility

    Shuo-Dong Wu; Zhen-Hai Zhang; Dong-Yan Li; Jun-Zhe Jin; Jing Kong; Zhong Tian; Wei Wang; Min-Fei Wang


    AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P<0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P<0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P<0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most

  15. Modulation of proton transfer in the water wire of dioxolane-linked gramicidin channels by lipid membranes.

    de Godoy, C M; Cukierman, S


    Proton conductance (g(H)) in single SS stereoisomers of dioxolane-linked gramicidin A (gA) channels were measured in different phospholipid bilayers at different HCl concentrations. In particular, measurements were obtained in bilayers made of 1,2-diphytanoyl 3-phosphocholine (DiPhPC) or its ethylated derivative 1,2-diphytanoyl 3-ethyl-phosphocholine (et-DiPhPC,). The difference between these phospholipids is that in et-DiPhPC one of the phosphate oxygens is covalently linked to an ethyl group and cannot be protonated. In relatively dilute acid solutions, g(H) in DiPhPC is significantly higher than in et-DiPhPC. At high acid concentrations, g(H) is the same in both diphytanoyl bilayers. Such differences in g(H) can be accounted for by surface charge effects at the membrane/solution interfaces. In the linear portion of the log g(H)-log [H] relationship, g(H) values in diphytanoyl bilayers were significantly larger (approximately 10-fold) than in neutral glyceryl monooleate (GMO) membranes. The slopes of the linear log-log relationships between g(H) and [H] in diphytanoyl and GMO bilayers are essentially the same (approximately 0.76). This slope is significantly lower than the slope of the log-log plot of proton conductivity versus proton concentration in aqueous solutions (approximately 1.00). Because the chemical composition of the membrane-channel/solution interface is strikingly different in GMO and diphytanoyl bilayers, the reduced slope in g(H)-[HCl] relationships may be a characteristic of proton transfer in the water wire inside the SS channel. Values of g(H) in diphytanoyl bilayers were also significantly larger than in membranes made of the more common biological phospholipids 1-palmitoyl 2-oleoyl phosphocholine (POPC) or 1-palmitoyl 2-oleoyl phosphoethanolamine (POPE). These differences, however, cannot be accounted for by different surface charge effects or by different internal dipole potentials. On the other hand, maximum g(H) measured in the SS channel

  16. 锦灯笼根和茎化学成分研究%Chemical constituents in roots and stems of Physalis alkekengi var. franchetii

    李兆春; 陈重; 李笑然; 许琼明; 杨世林


    To investigate the chemical constituents in the roots and stems of Physalis alkekengi var. franchetii. Methods The constituents were isolated by chromatography on silica , Sephadex LH-20 gel columns, medium pressure and semi-preparative HPLC and their structures were elucidated by chemical properties and spectroscopic analyses. Results Ten compounds were isolated and their structures were identified as P-sitosterol (1), daucosterol (2), luteolin (3), luteolin-7-O-β-O- glucoside (4), isofucosterol (5), glyceryl monostearate (6), withanolide A (7), daucosterol-6'-O-stearate (8), oleanolic acid (9), and (Z)-9, 10, 11-trihydroxy-12-octadecenoic acid (10). Conclusion Compounds 6, 8, and 10 are obtained from the plants in this genus for the first time. Compounds 5, 7, and 9 are obtained from this plant for the first time.%目的 研究锦灯笼Physalis alkekengi var.franchetii根和茎的化学成分.方法 利用硅胶柱色谱法、Sephadex LH-20凝胶柱色谱法、中压柱色谱及半制备高效液相色谱等方法分离纯化,通过核磁共振谱、质谱等光谱数据鉴定化合物结构.结果 分离得到10个化合物,分别鉴定为β-谷甾醇(1)、胡萝卜苷(2)、木犀草素(3)、木犀草素- 7-O-β-D-葡萄糖苷(4)、异岩藻甾醇(5)、硬脂酸单甘油酯(6)、睡茄内酯A(7)、胡萝卜苷-6 '-O-硬脂酸酯(8)、齐墩果酸(9)、(Z)-9,10,11-三羟基-12-十八碳烯酸(10).结论 化合物6、8、10为首次从该属植物中分离得到,化合物S、7、9为首次从该植物中分离得到.

  17. Design of lipid-based delivery systems for improving lymphatic transport and bioavailability of delta-tocopherol and nobiletin

    Xia, Chunxin

    Lymphatic drug transport can confer bioavailability advantage by avoiding the first-pass metabolism normally observed in the portal vein hepatic route. It was reported that long chain lipid-based delivery systems can stimulate the formation of chylomicron and thus promote the lymphatic transport of drugs. In this study, a novel delta-tocopherol (delta-T) loaded Solid Lipid Nanoparticle (SLN) system was developed to investigate its effect on promoting the lymphatic transport of delta-T. The delta-T SLN was prepared with hot melt emulsification method by using glyceryl behenate (compritol RTM888) as the lipid phase and lecithin (PC75) as the emulsifier. Formula configuration, processing condition and loading capacity were carefully optimized. Physicochemical properties (particle size, surface charge, morphology) were also characterized. Moreover, excellent stability of the developed delta-T SLN in the gastrointestinal environment was observed by using an in vitro digestion model. Further investigations of the SLN in stimulating delta-T lymphatic transport were performed on mice without cannulation. Compared with the control group (delta-T corn oil dispersion), much lower delta-T levels in both blood and liver indicated reduced portal vein and hepatic transport of delta-T in the form of SLN. On the other hand, significantly higher concentrations of delta-T were observed in thymus, a major lymphatic tissue, indicating improved lymphatic transport of delta-T with the SLN delivery system. Finally, the far less excreted delta-T level in feces further confirmed improved lymphatic transport and overall bioavailability of delta-T by using SLN system. Nobiletin (NOB), one of most abundant polymethoxyflavones (PMFs) found in Citrus genus, has a low solubility in both water and oil at ambient temperatures. Thus it tends to form crystals when the loading exceeds its saturation level in the carrier system. This character greatly impaired its bioavailability and application. To

  18. 丹参酮ⅡA 固体脂质纳米粒的制备及质量评价%Preparation and quality evaluation of tanshinonesⅡA solid lipid nanoparticles

    瞿继兰; 刘志东; 郭秀君; 庞晓晨; 韩真真


    [目的]以山嵛酸甘油酯和单硬脂酸甘油酯为载体材料制备丹参酮 IIA 固体脂质纳米粒(TA-SLN)并评价其质量。[方法]采用乳化固化法制备 TA-SLN,以包封率为指标,通过单因素考察法对处方进行优化,激光粒径测定仪测定其粒径、电位,并用差示扫描量热仪(DSC)表征其性质。[结果]制备的 TA-SLN 平均粒径为(110±4) nm,Zeta 电位为-34.4 mV,包封率为79.08%。DSC 表明其理化性质稳定可靠。[结论]采用乳化固化法制备的 TA-SLN 粒径和包封率较适宜,理化性质稳定,为开发其新制剂奠定了实验基础。%Objective] To prepare tanshinonesⅡA-loaded solid lipid nanoparticles with docosanoic acid glyceride and glyceryl monos-tearate as its lipid matrix and investigate its quality. [Methods] TanshinonesⅡA-loaded solid lipid nanoparticles were prepared by emul-sion evaporation-solidification. With encapsulation efficiency as index, through the single factor the formulation was optimized, using laser particle size analyzer its particle size was measured, Using potential and use DSC its properties was characterized. [Results] The obtained solid lipid nanoparticles had an average size of (110±4) nm, zeta potential was -38.5 mV and the entrapment efficiency was 79.08%. DSC showed that its physical and chemical properties were stable and reliable. [Conclusion] The solid lipid nanoparticles prepared by the emulsion evaporation-solidification have an appropriate size, the encapsulation efficiency and stable physical and chemical properties have provided an experimental foundation for the development of the new formulation.

  19. The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study.

    Kulbacka, Julita; Pucek, Agata; Wilk, Kazimiera Anna; Dubińska-Magiera, Magda; Rossowska, Joanna; Kulbacki, Marek; Kotulska, Małgorzata


    Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of

  20. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Maheshkumar P Soni


    Full Text Available Background: Buparvaquone (BPQ, a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES organs. The present study investigates development of solid lipid nanoparticles (SLN of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C. Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC, powder X-ray diffraction (XRD and scanning electron microscope (SEM study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8% and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52% uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed

  1. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  2. A novel mathematical model considering change of diffusion coefficient for predicting dissolution behavior of acetaminophen from wax matrix dosage form.

    Nitanai, Yuta; Agata, Yasuyoshi; Iwao, Yasunori; Itai, Shigeru


    From wax matrix dosage forms, drug and water-soluble polymer are released into the external solvent over time. As a consequence, the pore volume inside the wax matrix particles is increased and the diffusion coefficient of the drug is altered. In the present study, we attempted to derive a novel empirical mathematical model, namely, a time-dependent diffusivity (TDD) model, that assumes the change in the drug's diffusion coefficient can be used to predict the drug release from spherical wax matrix particles. Wax matrix particles were prepared by using acetaminophen (APAP), a model drug; glyceryl monostearate (GM), a wax base; and aminoalkyl methacrylate copolymer E (AMCE), a functional polymer that dissolves below pH 5.0 and swells over pH 5.0. A three-factor, three-level (3(3)) Box-Behnken design was used to evaluate the effects of several of the variables in the model formulation, and the release of APAP from wax matrix particles was evaluated by the paddle method at pH 4.0 and pH 6.5. When comparing the goodness of fit to the experimental data between the proposed TDD model and the conventional pure diffusion model, a better correspondence was observed for the TDD model in all cases. Multiple regression analysis revealed that an increase in AMCE loading enhanced the diffusion coefficient with time, and that this increase also had a significant effect on drug release behavior. Furthermore, from the results of the multiple regression analysis, a formulation with desired drug release behavior was found to satisfy the criteria of the bitter taste masking of APAP without lowering the bioavailability. That is to say, the amount of APAP released remains below 15% for 10 min at pH 6.5 and exceeds 90% within 30 min at pH 4.0. The predicted formulation was 15% APAP loading, 8.25% AMCE loading, and 400 μm mean particle diameter. When wax matrix dosage forms were prepared accordingly, the predicted drug release behavior agreed well with experimental values at each pH level

  3. Optimization of a novel wax matrix system using aminoalkyl methacrylate copolymer E and ethylcellulose to suppress the bitter taste of acetaminophen.

    Shiino, Kai; Iwao, Yasunori; Miyagishima, Atsuo; Itai, Shigeru


    The purpose of the present study was to design and evaluate a novel wax matrix system containing various ratios of aminoalkyl methacrylate copolymer E (AMCE) and ethylcellulose (EC) as functional polymers in order to achieve the optimal acetaminophen (APAP) release rate for taste masking. A two factor, three level (3(2)) full factorial study design was used to optimize the ratios of AMCE and EC, and the release of APAP from the wax matrix was evaluated using a stationary disk in accordance with the paddle method. The disk was prepared by congealing glyceryl monostearate (GM), a wax with a low melting point, with various ratios of polymers and APAP. The criteria for release rate of APAP from the disk at pH 4.0 and pH 6.5 were calculated to be more than 0.5017 microg/(mlxmin) and less than 0.1414 microg/(mlxmin), respectively, under the assumption that the particle size of spherical matrix should be 100 microm. In multiple regression analysis, the release of APAP at pH 4.0 was found to increase markedly as the concentration of AMCE increased, whereas the release of APAP at pH 6.5 decreased as the EC concentration increased, even when a high level of AMCE was incorporated. Using principle component analysis, it was found that the viscosity of the matrix affects the pH-dependent release of APAP at pH 4.0 and pH 6.5. Furthermore, using multiple regression analysis, the optimum ratio of APAP:AMCE:EC:GM was found to be 30:7:10:53, and the release pattern of APAP from the optimum wax formulation nearly complied with the desired criteria. Therefore, the present study demonstrated that the incorporation of AMCE and EC into a wax matrix system enabled the appropriate release of APAP as a means of taste masking. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  4. Superhydrophilic surfaces from short and medium chain solvo-surfactants

    Valentin Romain


    Full Text Available Pure monoglycerides (GM-Cs and glycerol carbonate esters (GCE-Cs are two families of oleochemical molecules composed of a polar part, glycerol for GM-Cs, glycerol carbonate for GCE-Cs, and a fatty acid lipophilic part. From a chemical point of view, GM-Cs include two free oxygen atoms in the hydroxyl functions and one ester function between the fatty acid and the glycerol parts. GCE-Cs contain two blocked oxygen atoms in the cyclic carbonate backbone and three esters functions: two endocyclic in the five-membered cyclic carbonate function, one exocyclic between the fatty acid and glycerol carbonate parts. At the physico-chemical level, GMCs and GCE-Cs are multifunctional molecules with amphiphilic structures: a common hydrophobic chain to the both families and a polar head, glycerol for GMs and glycerol carbonate for GCE-Cs. Physicochemical properties depend on chain lengths, odd or even carbon numbers on the chain, and glyceryl or cyclocarbonic polar heads. The solvo-surfactant character of GM-Cs and overall GCE-Cs were discussed through the measurements of critical micellar concentration (CMC or critical aggregation concentration (CAC. These surface active glycerol esters/glycerol carbonate esters were classified following their hydrophilic/hydrophobic character correlated to their chain length (LogPoctanol/water = f(atom carbon number. Differential scanning calorimetry and optical polarized light microscopy allow us to highlight the selfassembling properties of the glycerol carbonate esters alone and in presence of water. We studied by thermal analysis the polymorphic behaviour of GCE-Cs, and the correlation between their melting points versus the chain lengths. Coupling the self-aggregation and crystallization properties, superhydrophilic surfaces were obtained by formulating GM-Cs and GCE-Cs. An efficient durable water-repellent coating of various metallic and polymeric surfaces was allowed. Such surfaces coated by self-assembled fatty acid


    何秋; 王怀良; 章新华; 陈磊


    目的:探讨核转录因子-κB(nuclear factor-kappa B,NF-κB)在偏头痛脑膜炎症反应中的作用及细胞间黏附分子-1(intercellular adhesion molecules-1,ICAM-1)表达的调控机制.方法采用静脉注射(iv)硝酸甘油(glyceryl trinitrate,GTN)法建立大鼠偏头痛模型,分为对照组、模型组、溶剂对照组、吡咯烷二硫氨基甲酸(pyrrolidine dithiocarbamate,PDTC)组.各组分别包括0.9%生理盐水或GTN iv后1.5,4h两个实验小组.应用Western印迹法分别观察PDTC对GTN iv后1.5h大鼠脑膜NF-κB蛋白表达水平与GTN iv后4h ICAM-1蛋白表达水平的影响.结果:PDTC 50,100,200各剂量组GTN iv后1.5h大鼠脑膜NF-κB蛋白表达量较模型组分别降低30%(P<0.05)、52%(P<0.01)和65%(P<0.01),呈剂量依赖性;PDTC 50,100,200各剂量组GTN iv后4h大鼠脑膜ICAM-1蛋白表达量较模型组分别降低36%(P<0.05)、71%(P<0.01)和51%(P<0.01),无剂量依赖关系.结论:NF-κB参与偏头痛时脑膜ICAM-1的蛋白合成调控,在偏头痛的脑膜炎症机制中起着重要作用.

  6. 穴位埋线联合中药治疗不稳定型心绞痛临床观察%Clinical Observation on Treatment of Unstable Angina Pectoris with Catgut Embedding at Acupoints and Herbs

    范宗鹏; 吴玉姣


    目的:观察穴位埋线联合中药治疗不稳定型心绞痛临床疗效及副作用.方法:将临床确诊为不稳定型心绞痛患者348 例随机分为2 组,治疗组采用穴位埋线联合中药加常规西药治疗,对照组单纯应用常规西药治疗.2 组进行临床症状,心电图疗效及副作用对比分析.结果:治疗后在胸痛发作次数、持续时间及硝酸甘油耗量治疗组均明显低于对照组(P<0.01),治疗组治疗后心电图总ST 段,总T 波压低程度低于对照组(P<0.05).结论:穴位埋线联合中药加常规西药治疗不稳型心绞痛疗效满意,副作用少.%Objective: To observe clinical effects and adverse reactions of catgut embedding at acupoints and herbs in treating unstable angina pectoris. Method: All 348 patients proved with coronary heart disease and unstable angina pectoris were randomized into two groups. The treatment group received catgut embedding at acupoints, herbs and routine western medicine, the control group were applied with routine western medicine. Curative effects, EEG and side effects were compared and analyzed. Result: The treatment group was lower than the control group significantly in the attack times of chest pain, duration and consumption of glyceryl trinitrate after treating (P<0.05), the treatment group was lower than the control group after treating in depressed degrees of total ST segment and total T segment of ECG (P<0.05). Conclusion: Catgut embedding at acupoints, herbs and routine western medicine could obtain satisfactory effects in treating unstable angina pectoris with minor side-effects.

  7. Role of the N terminus in enzyme activity, stability and specificity in thermophilic esterases belonging to the HSL family.

    Mandrich, Luigi; Merone, Luigia; Pezzullo, Margherita; Cipolla, Laura; Nicotra, Francesco; Rossi, Mosè; Manco, Giuseppe


    A superposition between the structures of Alicyclobacillus acidocaldarius esterase 2 (EST2) and Burkholderia cepacia lipase, the latter complexed with a phosphonate inhibitor, allowed us to hypothesize for the EST2 N terminus a role in restricting the access to the active site and therefore in modulating substrate specificity. In order to test this hypothesis we generated by site-directed mutagenesis some truncated versions of EST2 and its double mutant M211S/R215L (S/L) at the N terminus. In parallel, an analysis of the Sulfolobus solfataricus P2 genome allowed us to identify a gene coding for a putative esterase of the HSL family having a natural deletion of the corresponding region. The product of this gene and the above-mentioned EST2 mutants were expressed in Escherichia coli, purified and characterised. These studies support the notion that the N terminus affects substrate specificity other than several other enzyme parameters. Although the deletions afforded a tenfold and 550-fold decrease in catalytic efficiency towards the best substrate pNP-hexanoate at 50 degrees C for EST2 and S/L, respectively, the analysis of the specific activities with different triacylglycerols with respect to pNP-hexanoate showed that their ratios were higher for deleted versus non-deleted enzymes, on all tested substrates. In particular, the above ratios for glyceryl tridecanoate were 30-fold and 14-fold higher in S/L and EST2 deleted forms, respectively, compared with their full-length versions. This behaviour was confirmed by the analysis of the S.solfataricus esterase, which showed similar specific activities on pNP-hexanoate and triacylglycerols; in addition, higher activities on the latter substrates were observed in comparison with EST2, S/L and their deleted forms. Finally, a dramatic effect on thermophilicity and thermostability in the EST2 deleted forms was observed. This is the first report highlighting the importance of the "cap" domain in the HSL family, since the N

  8. 大叶南五味子果实化学成分研究%Chemical Constituents from the Fruits of Kadsura marmorata

    王宏军; 武新亮; 周铁忠; 邓旭明; 王大成


    Objective:To study the chemical constituents from the fruits of Kadsura marmorata. Methods:The chemical constituents were isolated and purified by chromatography on silica gel,Sephadex LH-20 column and HPLC. Results:9 compounds were isolated and identified as 4,5-dihydroxy-3-methoxybiphenyl(Ⅰ) ,eriobofuran( Ⅱ ) ,30,16β-dihydroxy urs-12-ene(Ⅲ) ,2α,3β,6β,23- tetrahydroxy urs-12,18-dien-28-oic acid(Ⅳ) ,2α,3β,23-trihydroxy urs-12-en-28-oic acid(Ⅴ) ,rutin(Ⅵ) ,2-ethylhexanoic acid(Ⅶ) ,2-monolaurin(Ⅷ) ,glyceryl monoricinoleate (Ⅸ) on the basis of NMR and EI-MS spectroscopic analysis. Conclusion: All these compounds are isolated from this genus for the first time.%目的:研究大叶南五味子果实的化学成分.方法:采用硅胶柱层析、Sephadex LH-20 、HPLC等色谱技术进行分离纯化,NMR和EI-MS等波谱学方法进行结构鉴定,结果:从中分离得到9个化合物,分别鉴定为:4,5-二羟基-3-甲氧基二苯(Ⅰ)、eriobofuran (Ⅱ)、3β,16β-二羟基-12-烯-乌苏烷(Ⅲ)、2α,3β,6β,23-tetrahydroxy urs-12,18-dien28-oic acid(Ⅳ)、2α,3β,23-trihydroxy urs-12-en-28-oic acid(Ⅴ)、芦丁(Ⅵ) 、2-乙基己酸(Ⅶ)、2-月桂酸单甘油酯(Ⅷ)、单蓖麻油酸甘油酯(Ⅸ).结论:以上9个化合物均为首次从南五味子属植物中分离得到.

  9. Method developments approaches in supercritical fluid chromatography applied to the analysis of cosmetics.

    Lesellier, E; Mith, D; Dubrulle, I


    Analyses of complex samples of cosmetics, such as creams or lotions, are generally achieved by HPLC. These analyses are often multistep gradients, due to the presence of compounds with a large range of polarity. For instance, the bioactive compounds may be polar, while the matrix contains lipid components that are rather non-polar, thus cosmetic formulations are usually oil-water emulsions. Supercritical fluid chromatography (SFC) uses mobile phases composed of carbon dioxide and organic co-solvents, allowing for good solubility of both the active compounds and the matrix excipients. Moreover, the classical and well-known properties of these mobile phases yield fast analyses and ensure rapid method development. However, due to the large number of stationary phases available for SFC and to the varied additional parameters acting both on retention and separation factors (co-solvent nature and percentage, temperature, backpressure, flow rate, column dimensions and particle size), a simplified approach can be followed to ensure a fast method development. First, suited stationary phases should be carefully selected for an initial screening, and then the other operating parameters can be limited to the co-solvent nature and percentage, maintaining the oven temperature and back-pressure constant. To describe simple method development guidelines in SFC, three sample applications are discussed in this paper: UV-filters (sunscreens) in sunscreen cream, glyceryl caprylate in eye liner and caffeine in eye serum. Firstly, five stationary phases (ACQUITY UPC(2)) are screened with isocratic elution conditions (10% methanol in carbon dioxide). Complementary of the stationary phases is assessed based on our spider diagram classification which compares a large number of stationary phases based on five molecular interactions. Secondly, the one or two best stationary phases are retained for further optimization of mobile phase composition, with isocratic elution conditions or, when

  10. Chemical constituents from leaves of Ananas comosus and their biological activities%菠萝叶的化学成分及生物活性研究

    黄筱娟; 陈文豪; 纪明慧; 郭飞燕; 舒火明; 郑彩娟


    目的 研究菠萝Ananas comosus叶的化学成分及生物活性.方法 采用硅胶柱色谱、Sephadex LH-20柱色谱、重结晶等方法进行分离纯化,根据理化性质和波谱数据鉴定化合物结构,并对各化合物进行抗菌活性、卤虫致死活性测定.结果 从菠萝叶95%乙醇提取物中分离纯化得到8个化合物,分别鉴定为tricin-4'’-O-[10"-O-(8"-hydroxyl) feruloyl-(9"'-O-p-coumaroyl) glyceryl] ether (1)、2,4-二氯苯甲酸(2)、小麦黄素(3)、金圣草黄素(4)、1-O-对羟基肉桂酰单甘油酯(5)、1-O-阿魏酰单甘油酯(6)、1-O-阿魏酸-3-O-对羟基肉桂酰甘油酯(7)、1,3-二氧阿魏酰甘油酯(8).化合物1对金黄色葡萄球菌和大肠杆菌表现出与阳性对照环丙沙星相当的抑制活性,最小抑菌浓度(MIC)均达到0.156 μg/mL.卤虫致死活性结果显示,化合物1和4的ICso值分别为21.4、25.0 μtg/mL.结论 除化合物5外,其余化合物均首次从该植物中分离得到,其中化合物1为新化合物,命名为菠萝叶酯A,且有良好的抑菌活性和卤虫致死活性.

  11. Evaluating the link between self-assembled mesophase structure and drug release.

    Phan, Stephanie; Fong, Wye-Khay; Kirby, Nigel; Hanley, Tracey; Boyd, Ben J


    Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V(2)) and inverse hexagonal (H(2)) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I(2)) and inverse micelles (L(2)). The systems are comparable as they were all prepared from the one lipid, glyceryl monooleate (GMO), which sequentially forms all four phases with increasing hexadecane (HD) content in excess water. Phase identity was confirmed by small angle X-ray scattering (SAXS). SAXS data indicated that four mesophases were formed with increasing HD content at 25°C: V(2) phase (Pn3m space group) formed at 0-4% (w/w) HD, H(2) phase formed at 4-25% (w/w) HD, I(2) phase (Fd3m space group) formed at 25-40% (w/w) HD and finally L(2) phase formed at >40% (w/w) HD. Analogous compositions using phytantriol rather than GMO as the core lipid did not produce the I(2) phase, with only V(2) to H(2) to L(2) transitions being apparent with increasing HD concentration. In order to relate the liquid crystal phase structure to drug release rate, in vitro release tests were conducted by incorporating radio-labelled glucose as a model hydrophilic drug into the four GMO-based mesophases. It was found that the drug release followed first-order diffusion kinetics and was fastest from V(2) followed by L(2), H(2), and I(2). Drug release was shown to be significantly faster from bicontinuous cubic phase than the other mesophases, indicating that the state of the water compartments, whether open or closed, has a great influence on the rate of drug release. It is envisioned that liquid crystalline mesophases with slower release characteristics will more likely have potential applications as sustained release drug delivery systems, and hence

  12. 刺五加果肉化学成分的研究(Ⅱ)%Chemical Constituents from Pulp of Acanthopanax senticosus ( Maxim) Harms (Ⅱ)

    闫兆威; 刘金平; 卢丹; 李平亚


    Twelve compounds were isolated from the water extract of the pulp of Acanthopanax senticosus (Rupr. Et Maxim) Harms by various column chromatographic techniques. The structures were elucidated on the basis spectral data ( H NMR, 13 C NMR and MS) and chemical evidences. Their structures were determined as (-)-3,4-divanillyltetrahydrofuran (1)、(-)-savinin (2) 、5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (3)、Eleutheroside A (4)、Eleutheroside B (5)、Uracil (6)、2-furoic acid (7)、Succinic acid (8)、Phthalic acid bis-(2-ethyl-hexyl) ester (9)、Glyceryl monos-tearate (10)、Isoselachoceric acid (11) and Octadecane (12). Among them compounds 1、3、6 、7 、8 and 9 are isolated from this plant for the first time.%应用多种色谱技术进行分离纯化,从刺五加果肉水提取物中分离得到12个化合物,经理化性质和波谱分析鉴定其结构分别为:(-)-3,4-二香草基四氢呋喃(1)、桧脂素(2)、5α,8α-桥二氧麦角甾-6,22-双烯-3-醇(3)、刺五加苷A(4)、刺五加苷B(5)、尿嘧啶(6)、2-呋喃甲酸(7)、琥珀酸(8)、Phthalic acid bis-(2-ethyl-hexyl) ester (9)、硬脂酸甘油酯(10)、正二十四烷酸(11)和正三十八烷(12).其中化合物1、3、6、7、8和9为首次从本植物中分得.

  13. The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle.

    Sherif, Saly; Bendas, Ehab R; Badawy, Sabry


    Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy

  14. Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.

    Cristiane de Oliveira

    Full Text Available Studying the uptake of 2-deoxy glucose (2-DG analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor during mild and severe biliary AP.Wistar rats (300 g; 8-12/group were administered NIR 2-DG (10 nM; I.V.. Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g within 10 minutes of giving NIR 2-DG. Controls (CON only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP.NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality

  15. Enhanced oral absorption of 20(S-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

    Jin X


    Full Text Available Xin Jin,1,2 Zhen-hai Zhang,1 E Sun,1 Xiao-bin Tan,1 Song-lin Li,3 Xu-dong Cheng,4 Ming You,4 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China; 3Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China; 4ALG Bioscience Co, Ltd, Suzhou, People's Republic of ChinaBackground: 20(S-protopanaxadiol (PPD, similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases.Methods: In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo.Results: The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPD-cubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3 increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration–time curve (AUC0–∞ ] and PPD-cubosome containing piperine (AUC0–∞ compared to that of raw PPD (AUC0–∞ were 166

  16. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Malgorzata Zwolinska-Wcislo; Tomasz Brzozowski; Agata Ptak-Belowska; Aneta Targosz; Katarzyna Urbanczyk; Slawomir Kwiecien; Zbigniew Sliwowski


    AIM: To determine the eff ect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a nonselective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The eff ects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5- tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive aff erent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL.1β and TNF-α levels. These eff ects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF. These eff ects were restored by co

  17. The effect of peroxynitrite decomposition catalyst MnTBAP on aldehyde dehydrogenase-2 nitration by organic nitrates: role in nitrate tolerance.

    Mollace, Vincenzo; Muscoli, Carolina; Dagostino, Concetta; Giancotti, Luigino Antonio; Gliozzi, Micaela; Sacco, Iolanda; Visalli, Valeria; Gratteri, Santo; Palma, Ernesto; Malara, Natalia; Musolino, Vincenzo; Carresi, Cristina; Muscoli, Saverio; Vitale, Cristiana; Salvemini, Daniela; Romeo, Francesco


    Bioconversion of glyceryl trinitrate (GTN) into nitric oxide (NO) by aldehyde dehydrogenase-2 (ALDH-2) is a crucial mechanism which drives vasodilatory and antiplatelet effect of organic nitrates in vitro and in vivo. Oxidative stress generated by overproduction of free radical species, mostly superoxide anions and NO-derived peroxynitrite, has been suggested to play a pivotal role in the development of nitrate tolerance, though the mechanism still remains unclear. Here we studied the free radical-dependent impairment of ALDH-2 in platelets as well as vascular tissues undergoing organic nitrate ester tolerance and potential benefit when using the selective peroxynitrite decomposition catalyst Mn(III) tetrakis (4-Benzoic acid) porphyrin (MnTBAP). Washed human platelets were made tolerant to nitrates via incubation with GTN for 4h. This was expressed by attenuation of platelet aggregation induced by thrombin (40U/mL), an effect accompanied by GTN-related induction of cGMP levels in platelets undergoing thrombin-induced aggregation. Both effects were associated to attenuated GTN-induced nitrite formation in platelets supernatants and to prominent nitration of ALDH-2, the GTN to NO metabolizing enzyme, suggesting that GTN tolerance was associated to reduced NO formation via impairment of ALDH-2. These effects were all antagonized by co-incubation of platelets with MnTBAP, which restored GTN-induced responses in tolerant platelets. Comparable effect was found under in in vivo settings. Indeed, MnTBAP (10mg/kg, i.p.) significantly restored the hypotensive effect of bolus injection of GTN in rats made tolerants to organic nitrates via chronic administration of isosorbide-5-mononitrate (IS-5-MN), thus confirming the role of peroxynitrite overproduction in the development of tolerance to vascular responses induced by organic nitrates. In conclusion, oxidative stress subsequent to prolonged use of organic nitrates, which occurs via nitration of ALDH-2, represents a key event

  18. Effect of Various Additives on the Physical Properties of Polyvinylchloride Resin

    Imran Nazir Unar


    Full Text Available The compounding of Polyvinylchloride (PVC with some additives was studied for the enhancement of physical and mechanical properties. Two categories of formulations (un-plasticized and plasticized PVC were prepared with PVC (K value ranging from 60 to 70 taking as base polymer. Different additives generally categorized as plasticizers, fillers, stabilizers, pigments and processing aids, were mixed in the standard concentration unit “parts per hundred resins (phr” with base polymer. Cable compound and shoe compound were prepared in plasticized-PVC category containing mainly plasticizing additives like diisooctyl phthalate (DIOP (40 phr and epoxidized soybean oil (2-3 phr with general plasticizer (50-80 phr respectively. Whereas the rigid pipe and sheet compounds were prepared as un-plasticized PVC category containing different fillers/stabilizers like tribasic lead sulphate (6 phr, lead stearate (1 phr, glyceryl monostearate (0.4 phr in rigid pipe and butylin mercaptides (2-2.5 phr, fatty alcohol and fatty acid ester (0.5-0.8 phr in rigid sheet compound. Experimental investigation was carried out for analyzing the mechanical properties like tensile strength, elongation at break, hardness and physical property i.e. specific gravity for the compounded samples. An appreciable increase was observed in tensile strength from 460 Kg/cm2 (base PVC-polymer to a range of 550 Kg/cm2 for un-plasticized PVC compounds (rigid PVC-pipe and sheet with little increase in elongation at break from 56% (base polymer to 124.33% and 150% (for Pipe and Sheet compounds respectively. On the other side the elongation at break for plasticized PVC compounds was increased from 56% to 250.67% (for cable compound and 351.33% (for shoe compound, where as the tensile strength was decreased from 460 Kg/cm2 to 150.33 Kg/cm2 (for cable compound and 120.33 Kg/cm2 (for shoe compound. The hardness (shore A, D was increased from 40 to 80 for all the compounds except shoe compound

  19. A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

    Mojahedian, Mohammad M; Daneshamouz, Saeid; Samani, Soliman Mohammadi; Zargaran, Arman


    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron

  20. Relationship of levels of Vitamin D with flow-mediated dilatation of brachial artery in patients of myocardial infarction and healthy control: A case-control study

    Sarthak Malik


    Full Text Available Background: Cardiovascular diseases (CVD remain the leading cause of death worldwide. Vitamin D deficiency has been linked to increased risk of adverse CV events. Vitamin D deficiency may be responsible for endothelial dysfunction which in turn affects the onset and progression of coronary artery disease and its risk factors, directly or indirectly through various mechanisms. Materials and Methods: It was case-control study. A total of 50 cases of acute myocardial infarction (AMI (aged 40-60 years, admitted to medicine emergency/CCU, were taken as per ACC/AHA 2007 guidelines. An equal number of age- and sex-matched controls were also taken. Risk factors of AMI, flow-mediated dilatation (FMD, and 25(OHD levels were studied in all cases and controls. Correlation was also studied between FMD and 25(OHD. Results: The mean values of FMD were 18.86 ± 5.39% and 10.35 ± 4.90% in controls and cases, respectively (P < 0.05. The endothelial dilatation after glyceryl trinitrate (GTN was also studied and was found to be 26.175 ± 4.25% and 18.80 ± 5.72% in controls and cases, respectively (P < 0.05. The mean levels of 25(OHD in controls and cases were 25.45 ± 12.17 and 14.53 ± 8.28 ng/ml, respectively. In this study, 56% of subjects were Vitamin D deficient, 25% were Vitamin D insufficient, and only 19% had Vitamin D in normal range. A positive correlation coefficient was found between FMD and 25(OH Vitamin D levels (r = 0.841, P < 0.01. In this study, a positive correlation coefficient was also found between endothelial dilatation after GTN and 25(OHD levels (r = 0.743, P < 0.01. Conclusion: In this study, it was found that FMD was markedly impaired in patients of AMI when compared to controls. It was also found that majority of the study population was Vitamin D deficient; however, the deficiency was more severe in patients of AMI. We also found out that FMD was positively correlated (r = 0.841 to the deficiency state of Vitamin D in all the study

  1. Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein.

    Sara Janssen

    Full Text Available BACKGROUND: Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3 is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell. METHODS: Wild-type (WT and α-gustducin knockout (gust(-/- mice were fed a glyceryl trioctanoate-enriched diet (OD during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo. RESULTS: Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/- mice. Gastric emptying was accelerated in WT but not in gust(-/- mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels. CONCLUSION: This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.

  2. Box-Behnken响应面法优化吲哚美辛固体脂质纳米粒处方%Formulation Optimization of Indomethacin-loading Solid Lipid Nanoparticles by Box-Behnken Response Surface Methodology

    陈凯; 李收; 金凯; 赵晶; 郝吉福


    目的:优化吲哚美辛固体脂质纳米粒处方。方法:以吲哚美辛为模型药物、山嵛酸甘油酯为油相、泊洛沙姆188和聚乙二醇-12-羟基硬脂酸酯为乳化剂,以浊度、包封率、载药量为指标,采用Box-Behnken响应面法优化处方中油相用量、乳化剂-油相比例、药物-油相比例。采用扫描电镜、差示扫描热分析(DSC)表征固体脂质纳米粒的理化性质。结果:最优处方的油相用量为0.91%,乳化剂-油相比例为1∶1,药物-油相比例为1∶5;所制吲哚美辛固体脂质纳米粒的浊度为1025~1030 NTU,包封率为98.94%~99.08%,载药量为2.43%~2.46%,粒径为181.5~182.3 nm,多分散性指数(PDI)为0.340~0.341(n=3);DSC结果显示吲哚美辛不是以结晶状态存在于固体脂质纳米粒中。结论:成功筛选出最优处方,制得吲哚美辛固体脂质纳米粒。%OBJECTIVE:To optimize the formulation of indomethacin-loading solid lipid nanoparticle(SLN). METHODS:Us-ing indomethacin as model drug,glyceryl behenate as oil phase,poloxamer 188 and polyethylene glycol-12-hydroxystearic acid as emulsifier,with turbidity,entrapment efficiency and drug loading amount as index,Box-Behnken response surface methodology was used to optimize the amount of oil phase,emulsifier-oil phase ratio,drug-oil phase ratio. The physicochemical properties of SLNs were characterized by SEM and DSC. RESULTS:The optimal formulation was as follows as oil phase of 0.91%,emulsifier-oil ratio of 1∶1,drug-oil phase ratio of 1∶5. The turbidity,entrapment efficiency and drug loading amount of prepared nanoparticle were 1 025-1 030 NTU,98.94%-99.08%,2.43%-2.46%,respectively;particle size and polydispersity index(PDI)were 181.5-182.3 nm and 0.340-0.341(n=3). The results of DSC showed that indomethacin was not present in crystalline state dispersed into SLNs. CONCLUSIONS:The optimal formulation is screened successfully

  3. Synthesis of trimethylolpropane fatty acid diester-monoacetate by alkali catalysis%碱催化合成三羟甲基丙烷二脂肪酸一乙酸酯的研究

    王尔佩; KELVIN Windi; 唐书泽; 马祥; 汪勇


    Trimethylolpropane fatty acid triester( TFATE) was synthesized using corn oil deodorizer distill-ate as raw material, then TFATE was transesterified with glyceryl triacetate ( GTA) to produce renewable biolubricant base oil trimethylolpropane fatty acid diester-monoacetate ( TMP-DE-MA) . Trimethylol-propane potassium salt ( TMP-K) was used as catalyst, and the effects of reaction time, reaction tem-perature, molar ratio of reactants and catalyst dosage on the content of TMP-DE-MA were discussed. The results showed that the optimal synthesis conditions were obtained as follows:vacuum 800 Pa, reac-tion time 3 h, reaction temperature 190℃, molar ratio of TFATE to GTA 1∶1. 25, and molar ratio of TMP-K to GTA 0. 075∶1. Under the optimal conditions, the content of TMP-DE-MA in the product was 52. 56%. The average relative molecular weights of TFATE, TMP-DE-MA and trimethylolpropane fatty acid monoester-diacetate ( TMP-ME-DA) analysed by electrospray ionization mass spectrometry (ESI-MS) were 905. 9, 690. 8 and 435. 4, respectively.%研究以玉米油脱臭馏出物为原料制备三羟甲基丙烷脂肪酸三酯( TFATE ),通过TFATE与三乙酸甘油酯( GTA)酯交换制备可再生的生物润滑油基础油三羟甲基丙烷二脂肪酸一乙酸酯。使用三羟甲基丙烷钾( TMP-K)为催化剂,通过测定三羟甲基丙烷二脂肪酸一乙酸酯( TMP-DE-MA)在反应产物中的含量,探讨了反应时间、反应温度、反应物摩尔比、催化剂添加量对反应的影响。最佳合成条件为:真空度800 Pa,反应时间3 h,反应温度190℃, TFATE 与 GTA 摩尔比1∶1.25,催化剂TMP-K与GTA摩尔比0.075∶1。在最佳合成条件下,反应产物中TMP-DE-MA的含量为52.56%。经电喷雾离子化质谱(ESI-MS)分析,TFATE的平均相对分子质量为905.9, TMP-DE-MA的平均相对分子质量为690.8,三羟甲基丙烷一脂肪酸二乙酸酯( TMP-ME-DA)的平均相对分子质量为435.4。

  4. 中高含水油井防偏磨水基润滑液的研制与应用%Development and Application of Anti-Eccentric Wear Water-Based Lubricant for High and Medium Water-Cut Oil Wells



    为更好地延长中高含水期偏磨油井检泵周期,借鉴机械切削、磨削、拉拨、轧制和液压传动等领域广泛应用的水基润滑理论,以聚氧乙烯丙三醇硼酸酯硬脂酸酯、脂肪酸咪唑啉硼酸酯、两性表面活性剂SS-Z、聚氧乙烯烷基苯酚醚磺酸钠盐等为主剂,添加氟碳表面活性剂和维生素C合成了FYR-4水基润滑液.该润滑液体系中高反应活性的磷和氮、脂肪酸分子所形成的吸附膜和摩擦化学反应膜,具有优良的抗磨减摩性能和生物降解性.30余口油井的现场应用表明,油井日常维护中添加0.25%~0.50%的水基润滑液FYR-4后,检泵周期平均延长275 d,应用效果良好,为中高含水期油井偏磨治理提供了新途径.%In order to greatly prolong the checking period of pumps for the eccentric-wear oil wells in the medium and high water-cut periods,a water-based lubricating fluid FYR-4 has been synthesized based on the water-based lubrication theory widely applied in the fields, such as mechanical cutting, grinding, drawing, rolling and hydraulic transmission. The water-based lubricating fluid FYR-4 takes polyoxyethyl-ene glyceryl borate stearate,fatty acid imidazoline borate,amphoteric surfactant SS-Z,and polyoxyethylene alkyl phenol ether sulfonic aicd sodium as main agents,and with synergistic function of fluorocarbon sur-factant and vitamin C,jointly forming chemical reaction film and adsorption film with boundary lubricant on the surface of tubing pipe and sucker rod. The adsorption film and tribochemical reaction film were formed by highly reactive phosphor and nitrogen, functioning as carrier fatty acid molecule in the system with good friction-reduction and biodegradability. By adding FYR-4 water-based lubricating fluid of 0. 25%-0. 50% to 30 oil wells for routine maintenance,their average checking period of pumps has prolonged by 275 days or even longer, providing valuable reference for the eccentric-wear management of

  5. Effect of acupuncture liver channel of points on content of G protein alpha subunits in the rat brain stem after nitroglycerin infusion%针刺肝经腧穴对偏头痛大鼠脑干组织G蛋白含量的影响

    钟广伟; 李炜; 王素娥; 李臻琰; 文玲波


    目的研究针刺肝经腧穴对实验性偏头痛大鼠肝干组织G蛋白亚基(Gsa和Gia)含量的影响.方法通过皮下注射硝酸甘油(10mg/kg)建立实验性偏头痛大鼠模型,将动物随机分成正常对照组、生理盐水组、模型对照组和针刺治疗组,运用免疫印迹法(Western b1ot)检测脑干组织Gia和Gsa的含量.结果皮下注射硝酸甘油4h后脑干组织Gsa蛋白含量明显升高(P<0.01),Gia蛋白含量明显降低(P<0.01),Gsa/Gia蛋白比值升高;针刺治疗组与模型组比较,脑干组织中Gsa蛋白含量明显降低(P<0.01),Gia蛋白含量明显升高(P<0.01),Gsa/Gia蛋白比值降低.结论偏头痛发作可能与大鼠脑干组织G蛋白信号传导系统功能障碍有关,针刺介导的G蛋白信号通路可能是其防治偏头痛的重要机制之一.%Objective: In order to explore the effect of acupuncture the liver channel of points on the content of G protein alpha subunits in the rat brain stem after nitroglycerin infusion. Methods: The model of migraine rats were reproduced in accordance with Knynihar-tassorelli methods by infusing the NO lonor nitroglycerin [glyceryl trintrate (GTN)] i.h, then the rats were divided randomly into four groups: Normal control group, Saline control group, Model control group and Acupuncture treatment group. The content of Giα and Gsα protein in the rat brain stem was analysed by western blot method. Results: The model control group of the content of Gsα protein in the rat brain stem was significantly raised (P <0.01), the Giα protein was significantly reduced (P <0.01), and the ration of Gsα/Giα was increased by comparison with the normal control group. The acupuncture group of Gsα protein in the rat brain stem went up apparently than the model group (P <0.01), and Giα protein was slightly higher than the model group (P <0.01), resulting in reducing of Gsα/Giα rations. Conclusion: Our results provided important information for understanding how

  6. 基于液相色谱与质谱联用技术的良性前列腺肥大小鼠血清代谢组学分析%Serum metabolomics analysis on benign prostate hyperplasia in mice based on liquid chromatography-mass spectrometry

    耿越; 孙丰霞; 马玉; 邓立刚; 吕建云; 李腾; 王聪聪


    良性前列腺肥大已成为影响老龄男性生活质量的一个常见因素,其发病机制迄今尚未完全阐明。本研究采用超高压液相色谱-四极杆飞行时间串联质谱( UPLC-QTOF-MS)技术检测正常小鼠、良性前列腺肥大和非那雄胺干预的模型小鼠血清中代谢物的变化,对3组小鼠的血清代谢谱进行了分析。采用偏最小二乘-判别分析( PLS-DA)对3组小鼠代谢物分类并寻找潜在生物标志物。数据显示,3组小鼠的血清代谢物谱得到了很好的区分,发现并鉴定了3个潜在生物标志物,分别为1-棕榈酰溶血磷脂酰胆碱、1-O-十六烷基-2-O-乙酰基-SN-甘油基-3-磷酸胆碱和( Z)-13-二十二烯酰胺。结果表明良性前列腺肥大的发生与脂质代谢紊乱密切相关。%Benign prostatic hyperplasia( BPH)increasingly becomes a common factor affecting the quality of life of aging men. Its pathogenesis has not yet been fully elucidated. Ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS) was employed to detect the changes of serum metabolites in normal mice,benign prostatic hyperplasia model mice and BPH model mice with finasteride intervention. The serum metabo-lite profiles of the three groups of mice were analyzed. Partial least squares-discriminant analy-sis( PLS-DA)was used for group differentiation and biomarker selection. The results showed good distinction among the three groups of mice serum metabolite spectra. Three potential bio-markers, 1-hexadecanoyl-SN-glycero-3-phosphocholine, 1-O-hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine and( Z)-13-docosenamide,were discovered and identified. They all indica-ted the occurrence of benign prostatic hypertrophy is closely related to the disorders of lipid metabolism. Compared with the control group,the contents of the first two substances were significantly increased in the serum of BPH model mice,and significantly

  7. A systematic review and meta-analysis of the treatment of anal fissure.

    Nelson, R L; Manuel, D; Gumienny, C; Spencer, B; Patel, K; Schmitt, K; Castillo, D; Bravo, A; Yeboah-Sampong, A


    Anal fissure has a very large number of treatment options. The choice is difficult. In an effort to assist in that, choice presented here is a systematic review and meta-analysis of all published treatments for anal fissure that have been studied in randomized controlled trials. Randomized trials were sought in the Cochrane Controlled Trials Register, Medline, EMBASE and the trials registry sites and who/int/ictrp/search/en. Abstracts were screened, full-text studies chosen, and finally eligible studies selected and abstracted. The review was then divided into those studies that compared two or more surgical procedures and those that had at least one arm that was non-surgical. Studies were further categorized by the specific interventions and comparisons. The outcome assessed was treatment failure. Negative effects of treatment assessed were headache and anal incontinence. Risk of bias was assessed for each study, and the strength of the evidence of each comparison was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. One hundred and forty-eight eligible trials were found and assessed, 31 in the surgical group and 117 in the non-surgical group. There were 14 different operations described in the surgical group and 29 different non-surgical treatments in the non-surgical group along with partial lateral internal sphincterotomy (LIS). There were 61 different comparisons. Of these, 47 were reported in 2 or fewer studies, usually with quite small patient samples. The largest single comparison was glyceryl trinitrate (GTN) versus control with 19 studies. GTN was more effective than control in sustained cure (OR 0.68; 95% CI 0.63-0.77), but the quality of evidence was very poor because of severe heterogeneity, and risk of bias due to inadequate clinical follow-up. The only comparison to have a GRADE quality of evidence of high was a subgroup analysis of LIS versus any medical therapy (OR 0.12; CI 0

  8. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor

    Wood Paul L


    Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens (ether glycerophosphoethanolamine lipids are decreased in these genetic disorders. The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid (PPI-1011 to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 (RCDP1 and rhizomelic chrondrodysplasia punctata type 2 (RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis. We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease (PMD lymphocytes which possess a proteolipid protein-1 (PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum (ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency. Results In both RCDP1 and RCDP2 lymphocytes, PPI-1011 repleted the target ethanolamine plasmalogen (PlsEtn16:0/22:6 in a concentration dependent manner. In addition, deacylation/reacylation reactions resulted in repletion of PlsEtn 16:0/20:4 in both RCDP1 and RCDP2 lymphocytes, repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP2 lymphocytes, and partial repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP1 lymphocytes. In the Pex7 mouse, oral dosing of labeled PPI-1011 demonstrated repletion of tissue levels of the target plasmalogen PlsEtn 16:0/22:6 with phospholipid remodeling also resulting in significant repletion of PlsEtn 16:0/20:4 and PlsEtn 16:0/18:1. Metabolic conversion of PPI-1011 to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI-1011 is activated

  9. Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat.

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan


    In Thai traditional medicine, rhizomes of Kaempferia parviflora (KP) have been used for treating hypertension and for the promotion of longevity with good health and well being. Ageing is one of the most important risk factors for development of cardiovascular disease. To investigate whether a 6 weeks oral administration of a dichloromethane extract of fresh rhizomes of Kaempferia parviflora (KPD) had any effects on vascular functions, on the accumulation of lipid, as well as on any signs of gross organ toxicity in middle-aged rats. Fresh rhizomes of Kaempferia parviflora were first macerated twice with 95% ethanol to remove the dark color before extracting three times with 100% dichloromethane. The dichloromethane extract was evaporated under reduced pressure to obtain the dried Kaempferia parviflora dichloromethane extract (KPD). The rats were orally administered with the KPD at a dosage of 100mg/kg body weight, or with the same volume of the vehicle (tween 80, 0.2g: carboxy-methylcellulose sodium, 0.2g: distilled water 10 ml) once or twice a day for 6 weeks. Vascular functions were studied on isolated thoracic aorta and the mesenteric artery. The vascular eNOS enzyme was measured by Western blot analysis. Blood chemistry was measured by enzymatic methods. Liver cell lipid accumulation was measured using oil red O staining. A 6 weeks treatment of KPD once a day had no significant effects on any of the studied parameters. When the KPD was given twice a day, the contractile responses to phenylephrine of the thoracic aorta and mesenteric artery were lower than the vehicle control group, and this effect was abolished by N(G)-nitro-l-arginine or by removal of the vascular endothelium. Vasorelaxation to acetylcholine, but not to glyceryl trinitrate, by the thoracic aortic and mesenteric ring precontracted with phenylephrine was higher from the KPD treated rats than those from the vehicle control groups. Western blot analysis showed a higher quantity of thoracic- and

  10. Desarrollo y validación de un método por cromatografía en capa delgada para los estudios de estabilidad del naproxeno Development and validation of a thin-layer chromatography method for stability studies of naproxen

    Yaslenis Rodríguez Hernández


    Full Text Available Se realizó la validación de un método analítico con vistas a su aplicación en los estudios de estabilidad de las futuras formulaciones de supositorios de naproxeno para uso infantil y adulto. Se determinaron los factores que más influyeron en la estabilidad del naproxeno; la mayor degradación ocurrió en el medio ácido, oxidante y por acción de la luz. Se determinó la posibilidad de formación de ésteres entre el grupo carboxilo libre presente en el naproxeno y el monoestearato de glicerilo presente en la base como una de las vías de degradación en la nueva formulación; se obuvieron resultados satisfactorios. Se desarrolló un método por cromatografía en capa delgada y se seleccionaron las mejores condiciones cromatográficas. Se emplearon placas de sílica gel GF254 y revelador ultravioleta a 254 nm. Se evaluaron 3 sistemas de disolventes entre los cuales el A, compuesto por: acético glacial:tetrahidrofurano:tolueno (3:9:90 v/v/v, permitió una adecuada resolución entre el analito y los posibles productos de degradación, con un límite de detección de 1 µg. La aplicación del método propuesto se limitó a la identificación de los posibles productos de degradación solo con fines cualitativos y no como prueba límite. El método fue suficientemente sensible y selectivo para aplicarlo con el objetivo para el cual fue diseñado, según los resultados obtenidos en la validación.The validation of an analytical method was carried out to be applied to the stability studies of the future formulations of naproxen suppositories for infant and adult use. The factors which mostly influenced in the naproxen stability were determined, the major degradation occurred in oxidizing acid medium and by action of light. The possible formation of esters between the free carboxyl group present in naproxen and the glyceryl monoestereate present in the base was identified as one of the degradation paths in the new formulation. The results were

  11. Preparation of New Amphiphilic Liquid-Crystal Diblock Copolymers Bearing Side-on Cholesteryl Mesogen and Their Self-aggregation%具有侧挂胆固醇液晶元的两亲嵌段功能大分子的合成及自组装研究

    胡方振; 陈圣典; 李慧; 孙景景; 盛瑞隆; 罗挺; 曹阿民


    采用可逆加成-断裂链转移(RAFT)聚合法,合成了系列具有刚性疏水胆固醇液晶元的聚甲基丙烯酸甘油酯-嵌段-聚甲基丙烯酸亚己基胆固醇酯(PGMA-b-PMA6Chol)两亲嵌段功能大分子.运用核磁共振(NMR)和凝胶渗透色谱(GPC)表征了其化学结构及分子量,并对其热性质、液晶相结构及相转变行为分别运用热台偏振光显微镜(POM)、热重分析仪(TGA)、示差扫描量热仪(DSC)和二维小角X射线散射(2D-SAXS)表征.采用纳米沉淀法研究了所得嵌段大分子的溶液自组装,动态光散射(DLS)和扫描电子显微镜(SEM)的研究发现溶液自组装聚集体为尺寸0.7~2.0rn的球形结构,其中含有较高刚性链段质量比例的嵌段大分子组装形成开口中空结构的聚集体,且其尺寸随着溶液温度的升高减小,呈现可逆温度变化响应性.结果表明刚性疏水胆固醇液晶单元和具有多羟基结构的亲水性甲基丙烯酸甘油酯的嵌段共聚可以调控该类嵌段大分子自组装及溶液聚集体形貌.%Amphiphilic block copolymers bearing rigid hydrophobic liquid crystal mesogen have recently attracted broad interests since they could spontaneously self-assemble into functional objects at the micron and/or nanometer scales, and these soft matters bearing high-order hierarchical structures have potential applications in micro-reactors, advanced catalysts, biosensors, drug delivery, biotechnology and so forth. In this work, we designed and successfully prepared a new series of amphiphilic liquid crystal poly(glyceryl methaciylate)-b-poly(6-cholesteryloxyhexyl methacrylate) (PGMA-b-PMA6Chol) with hydrophobic PMA6Chol block bearing end-on cholesteryl mesogen through sequential controlled reversible addition-fragmentation chain transfer polymerization (RAFT) and successive removal of ketal protection groups. Then, their structures and comonomer composition were examined by nuclear magnetic resonance (NMR) and gel permeation

  12. 2型糖尿病早期内皮依赖性血管舒张功能的临床研究%Clinical investigation on the endothelium-dependent vasodilation function in the early stage of type 2 diabetes mellitus

    赵昉; 邓小戈; 苏文静; 赵国宁


    Objective To study the alteration of endothelium-dependent vasodilation in the early stage of type 2 diabetes mellitus (T2DM). Methods 44 T2DM patients without vascular complications (T2DM) and 40 normal subjects (NC) were recruited. Fasting plasma levels of glucose(FPG), insulin(FIns), hemoglobin A1c (HbA1c), total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol (HDL-C), Low density lipoprotein-cholesterol(LDL-C), uric acid( UA), nitric oxide(NO) and endothelin- 1 (ET- 1) were measured. Oral 75g glucose tolerance test was performed. The inner diameter of brachial artery and carotid artery and the intima-media thickness (IMT) of carotid artery were assayed by a high-resolution ultrasound system before and after reactive hyperemia. Vasodilation function was calculated as percent change in brachial artery diameter before and 1 min after reactive hyperemia (endothelium-dependent), and after sublingual glyceryl- trinitrate (endothelium-independent) therapy. Results FPG, FIns, 2hPG, HbA1c, TC, TG, HDL-C, LDL-C, HOMA-IR, NO and ET-1 were significantly different between T2DM and NC groups (P<0. 05 or P<0. 01 ). There were no significant differences between the two groups in age, sex, BMI, SBP, DBP and UA(P>0. 05). Flow-mediated and GNT-induced vasodilation were lower in T2DM group than in NC group (all P<0. 01). Conclusion The endothelium-dependent vasodilation and the endothelium-independant vasodilation are decreased in the early stage of T2DM.%目的 探讨2型糖尿病(T2DM)早期患者血管内皮功能的变化及其临床意义.方法 选择44例新诊断无并发症的T2DM早期患者和40名年龄、性别等匹配的正常对照者.采集空腹静脉血测定FPG、FIns、HbA1c、TC,TG、HDL-C、LDL-C、UA、NO、内皮素1(ET-1)等,并行75g葡萄糖耐量试验测定2hPG.采用高分辨率血管外彩超测定肱动脉、颈动脉的血管内径及颈动脉内膜中层厚度(IMT),以反应性充血前后血管内径变化百分

  13. Preparation, characterization and evaluation of moisturizing and UV protecting effects of topical solid lipid nanoparticles

    Shiva Golmohammadzadeh


    Full Text Available Solid lipid nanoparticles (SLN were recently proposed as carriers for various pharmaceutical and cosmetic actives. These lipid nanoparticles can act as moisturizers and physical sunscreens on their own. Therefore, the full potential of these carriers has yet to be determined. The present study was aimed to determine and compare moisturizing and UV-protecting effects of different solid lipid nanoparticles (SLN prepared by different solid lipids including Glyceryl monostearate (GMS, Precirol® (P and cetyl palmitate (CP as carrier systems of moisturizers and sunscreens. The influence of the size and matrix crystallinity of the solid lipids on the occlusive factor, skin hydration and UV-protection were evaluated by in vitro and in vivo methods. The SLN were prepared by high-shear homogenization and ultrasound methods. Size, zeta potential and morphological characteristics of the samples were assessed by transmission electron microscopy (TEM and thermotropic properties with differential scanning calorimetry (DSC technique. Results of the assessments showed that SLN-CP significantly increases skin hydration and UV-protection, compared to SLN-GMS and SLN-P. It was demonstrated that the size of SLN, crystallinity index of solid lipid in SLN and probably other mechanisms besides the occlusive factor can influence skin hydration and UV-protection indices. Furthermore, findings of the assessments demonstrated significant difference between in vitro and in vivo assessments regarding occlusive factor and moisturizing effects. Findings of the present study indicate that the SLN-CP could be a promising carrier for sunscreens and moisturizers.Nanopartículas lipídicas sólidas (NLS foram, recentemente, propostas como carreadores de vários ativos cosméticos e farmacêuticos. Essas nanopartículas lipídicas podem atuar como hidratantes e protetores solares físicos por si só. Assim sendo, determinou-se o potencial desses carreadores. Os objetivos do

  14. Metabonomic study on Siwu Tang in radiation-induced blood deficient mice%四物汤对辐射致血虚证小鼠作用的代谢组学研究

    马增春; 霍超; 周思思; 邵帅; 梁乾德; 王宇光; 谭洪玲; 肖成荣; 高月


    Objective: To study the radiation-induced Wood deficiency and the combination of prescription and syndrome of Siwu Tang using ultra performance liquid chromatography-quadrupoles-time of flight mass spectrometer (UPLC-ESI-Q-TOF-MS), in order to discover the changes in metabolic profiles of blood deficient mice induced by radiation, and clarify the relationship between blood deficient syndrome and the mechanism of Siwu Tang. Method: Thirty six C57 mice were randomly divided into three groups: the control group and the model model groups and the Siwu Tang group. The model was established by general irradiation with 3.5Gy60 Coy ray. The animals were sacrificed on the 7th day after radiation and their blood, spleens and thymus were collected and detected using UP1X-ESI-Q-TOF/MS. MarkerLynx XS software was adopted to identify chromatographic peaks in the total ion chromatogram. Data was processed by making principal component analysis and analyzed by orthogonal partial least squares method among these groups, in order to rapidly identify marks through pattern recognition and analysis. Result: Compared with the control group, lysophosphatide, glucosiduronic acid, monoacylglycerol, erythronic acid, ceramide, aspartate phosphate ester, glyceryl phosphatide were obviously changed in the sera of the model group. Monoacylglycerol, ceramide, lysophosphatide, hydroxybutyric acid, palmitinic acid, 3-hydrox-y-stearic acid, diethylarginine, neuraminic acid, phosphatidylserine were found in metabolites of their spleens. Methyladenosine, sitos-terol, carnitine, phosphatidylinositol, pbosphatidylethanolamine, diglyceride, dimethylargiiune, ceramide, hydroxybutyric acid, cholesterol were found in thymus of the model group. Conclusion: Analysis on physiological functions of these biological markers show that radiation could induce the disorder of the metabolism of lipoid and carbohydrate and affect the synthesis of some amino acids, and Siwu Tang can reverse these effects.%目的:基

  15. Calcium channel blockers for inhibiting preterm labour and birth.

    Flenady, Vicki; Wojcieszek, Aleena M; Papatsonis, Dimitri N M; Stock, Owen M; Murray, Linda; Jardine, Luke A; Carbonne, Bruno


    with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to substantial heterogeneity, outcome data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment or perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48). Calcium channel blockers resulted in an increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63 to 0.87). No difference was shown in one trial of outcomes at nine to twelve years of age.Comparing CCBs with ORA, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and