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Sample records for glyceryl trinitrate gtn

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

    PubMed

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

    2003-09-01

    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 g.kg-1.min-1, 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, <5 nM. There were no changes in maternal and fetal mean arterial pressure and heart rate or in uterine activity. Overall, the steady-state [GTN] was established by 5 min, and the UV/MA ratio of [GTN] was 0.18. The FA [GTN] (<5 nM) indicates that the fetus cleared essentially all GTN in the UV, and the maternal and fetal heart rate and mean arterial pressure appear to be independent of maternal GTN infusion.

  2. Biodegradation of glyceryl trinitrate by Penicillium corylophilum Dierckx.

    PubMed Central

    Zhang, Y Z; Sundaram, S T; Sharma, A; Brodman, B W

    1997-01-01

    Penicillium corylophilum Dierckx, isolated from a contaminated water wet, double-base propellant, was able to completely degrade glyceryl trinitrate (GTN) in a buffered medium (pH 7.0) containing glucose and ammonium nitrate. In the presence of 12 mg of initial fungal inoculum, GTN (48.5 to 61.6 mumol) was quantitatively transformed in a stepwise process to glyceryl dinitrate (GDN) and glyceryl mononitrate (GMN) within 48 h followed by a decrease in the GDN content with a concomitant increase in the GMN level. GDN was totally transformed to GMN within 168 h, and the complete degradation of GMN was achieved within 336 h. The presence of glucose and ammonium nitrate in the growth medium was essential for completion of the degradation of GTN and its metabolites. Complete degradation of GTN by a fungal culture has not been previously reported in the literature. PMID:9143106

  3. Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease.

    PubMed

    Franks, A G

    1982-01-09

    The effects of topical glyceryl trinitrate in Raynaud's disease were compared with those of placebo in a double-blind, crossover trial in 17 patients with bilateral Raynaud's disease and an associated collagen disease, who were receiving oral sympatholytic agents at the maximum levels they could tolerate. 1% glyceryl trinitrate ointment or a placebo of lanolin was applied to one hand only for 6 weeks, then patients changed to the other preparation for 6 weeks. The results were evaluated every 2 weeks. The frequency of attacks, severity of attacks, and size of ulcers in the treated hand were significantly lower when the patients were using glyceryl trinitrate ointment than when they were using placebo. The treatment of Raynaud's disease may be improved by using topical glyceryl trinitrate ointment as an adjunct to a basic regimen of oral sympatholytic agents. Glyceryl trinitrate ointment may obviate the need for more aggressive treatment, such as intraarterial reserpine, in selected patients.

  4. H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a purinergic receptor-dependent pathway

    PubMed Central

    Cortier, Marion; Boina-Ali, Rahamata; Racoeur, Cindy; Paul, Catherine; Solary, Eric; Jeannin, Jean-François; Bettaieb, Ali

    2015-01-01

    High doses of the organic nitrate glyceryl trinitrate (GTN), a nitric oxide (NO) donor, are known to trigger apoptosis in human cancer cells. Here, we show that such a cytotoxic effect can be obtained with subtoxic concentrations of GTN when combined with H89, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide.2HCl. This synergistic effect requires the generation of reactive oxygen species (ROS) from H89 and NO from GTN treatment that causes cGMP production and PKG activation. Furthermore, the GTN/H89 synergy was attenuated by inhibition of P2-purinergic receptors with suramin and competition with ATP/UDP. By down-regulating genes with antisense oligonucleotides, P2-purinergic receptors P2X3, P2Y1, and P2Y6 were found to have a role in creating this cytotoxic effect. Thus, H89 likely acts as an ATP mimetic synergizing with GTN to trigger apoptosis in aggressive cancer cells. PMID:25762630

  5. Improved preservation of the rat heart with celsior solution supplemented with cariporide plus glyceryl trinitrate.

    PubMed

    Gao, Ling; Hicks, Mark; MacDonald, Peter S

    2005-08-01

    Our aim was to investigate whether the addition of glyceryl trinitrate (GTN), a source of nitric oxide, and/or cariporide, a Na/H exchange inhibitor, to a commercial preservation solution (Celsior) improved and extended cardiac preservation. After baseline indices of cardiac function (aortic flow, coronary flow, heart rate, cardiac output) were measured in an isolated working rat heart model, hearts were arrested and stored at 2-3 degrees C for 6 or 10 h in Celsior solution alone, Celsior supplemented with either 0.1 mg/mL GTN or 10 microM cariporide or both. After storage, functional measurements were repeated and recovery of each parameter was expressed as a percentage of its pre-storage baseline. After 6 h storage, recovery of cardiac function was significantly better in hearts stored in GTN- or cariporide-supplemented Celsior solution compared with Celsior solution alone. The beneficial effect of GTN was significantly abrogated in hearts perfused with glibenclamide prior to storage. Significant recovery of cardiac function after 10 h storage was only observed in hearts stored in Celsior solution supplemented with both GTN and cariporide. Combined supplementation with GTN and cariporide extends the safe period of storage of the rat heart and may be a useful approach to enhancing preservation of the donor heart.

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

    PubMed Central

    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

    2016-01-01

    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

  7. Glyceryl Trinitrate Ointment Did Not Reduce Pain After Stapled Hemorrhoidectomy: A Randomized Controlled Trial

    PubMed Central

    Cross, Trent; Bartlett, Lynne; Mushaya, Chrispen; Ashour, Mohamed; Ho, Yik-Hong

    2012-01-01

    Medications, including topical 0.2% glyceryl trinitrate (GTN), can reduce anal spasm and pain after excisional hemorrhoidectomy. GTN after stapled hemorrhoidopexy was compared with routine postoperative management. Patients with symptomatic grade 3/4 hemorrhoids were recruited. After stapled hemorrhoidopexy, residual perianal skin tags were excised as appropriate. Those requiring double purse-string mucosectomy were excluded. Postoperative pain, pain duration, and complications were assessed. One hundred ten patients (74 men; mean age 50.6 years) were enrolled in the control group and 100 patients (57 men; mean age 49.8 years) in the GTN group. Maximum pain was higher in the GTN group (P  =  0.015). There were no differences between the two groups in residual perianal skin tags requiring excision, postoperative complications, recurrence rates, follow-up period, average pain, duration of pain, or satisfaction scores. Sixteen GTN patients were noncompliant due to side effects. None had persistent perianal skin tags. GTN did not reduce postoperative pain after stapled hemorrhoidectomy. PMID:23102076

  8. Comparative study of glyceryl trinitrate ointment versus surgical management of chronic anal fissure.

    PubMed

    Tauro, Leo Francis; Shindhe, Vittal V; Aithala, P Sathyamoorthy; Martis, John J S; Shenoy, H Divakar

    2011-08-01

    Chronic Anal Fissure (CAF) is common perineal condition and well-known painful entity. Standard surgical treatment even though available, may require long hospital stay and sometimes have worrying complications like anal incontinence. So non-surgical treatment, Glyceryl Trinitrate has been shown to be an effective for chronic anal fissure. It decreases anal tone and ultimately heals the anal fissure. The present study is the attempt to know the efficacy of 0.2% Glyceryl Trinitrate ointment in the treatment of chronic anal fissure and to compare the effectiveness of 0.2% Glyceryl Trinitrate ointment (GTN) versus fissurectomy with lateral internal sphincterotomy (LIS) and fissurectomy with posterior internal sphincterotomy (PIS) in the management of chronic anal fissure. This is a prospective comparative study of management of chronic anal fissure done in our hospital during the period of one and half year from October 2005 to March 2007. Thirty patients treated with 0.2% Glyceryl Trinitrate ointment and 30 patients treated with fissurectomy and lateral internal sphincterotomy and 30 patients treated with posterior internal sphincterotomy, for chronic anal fissure were selected for study. A single brand of 0.2% Glyceryl Trinitrate ointment (Nitrogesic) used for trial arm. Dose of administration was 1.5 cm to 2 cm in the anal canal with device provided by manufacturers of the proprietary preparation and applied twice a daily for 12 weeks. Patients were followed up for 12 weeks and thereafter evaluated for relief of symptoms in all three groups. Observations were recorded at 2 weeks; 6 weeks and 12 weeks of follow up period, regarding symptoms like pain and bleeding during defecation, healing of CAF and also for side effects like headache in GTN group and flatus, fecal incontinence in surgical groups. Data collected in proforma and analyzed. Study revealed CAF was more in male 59 patients (66%) than the female 31 patients (34%), the ratio being 1: 0.52. The

  9. Sublingual glyceryl trinitrate during colonoscopy and terminal ileal intubation: a randomized controlled trial.

    PubMed

    Hill, Patsy-Anne; Panteleimonitis, Sofoklis; McKay, Graham; Watson, Carol; Prach, Andre; Macdonald, Angus

    2017-02-01

    Background and aims Sublingual glyceryl trinitrate has been used as an aid to cannulate the Sphincter of Oddi during endoscopic retrograde cholangiopancreatography. Its role in terminal ileal intubation during colonoscopy is unknown. This study examines the role of sublingual glyceryl trinitrate in terminal ileal intubation during colonoscopy. Methods A triple-blind randomized controlled trial comparing sublingual glyceryl trinitrate (800 µg) vs. placebo (saline) in relation to terminal ileal intubation during colonoscopy was performed. Following caecal intubation, participants received sublingual glyceryl trinitrate/placebo followed by a 2-min observation period before intubation was attempted. Data on time to intubate the terminal ileum and intubation rate were collected. Results A total of 110 patients (age: 58 years (18-75)) were recruited and randomised as per protocol: 54 received sublingual glyceryl trinitrate. Terminal ileal intubation was successful in all patients receiving sublingual glyceryl trinitrate and in 53 (94.6%) of those receiving saline ( p = 0.243: Fischer's exact). The median time taken for ileal intubation after application of spray was 72.5 (7-900) s in the glyceryl trinitrate group compared with 125 (5-900) s in the placebo group ( p = 0.150: Mann-Whitney). There were no major adverse events reported in either group. Conclusions Terminal ileal intubation rates and timing were very good in both groups. Routine sublingual glyceryl trinitrate was not proven to be beneficial in improving terminal ileal intubation or intubation success rates in the hands of experienced colonoscopists. However, trends in this small study might suggest that glyceryl trinitrate could be useful in the hands of less experienced colonoscopists or in difficult terminal ileal intubation cases.

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

    PubMed

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

    2013-07-01

    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 2.5.1.18) 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.

  11. Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo

    PubMed Central

    Laight, David W; Kengatharan, K M; Gopaul, Nitin K; Änggård, Erik E; Carrier, Martin J

    1998-01-01

    We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic, chain-breaking antioxidants vitamin E (0.5% w w−1) or probucol (0.5% w w−1) or the superoxide anion scavenger tiron (1% w v−1 in drinking water).The basal plasma level of the isoprostane 8-epi-PGF2α, an in vivo marker of lipid peroxidation, was elevated by approximately 5 fold in the obese Zucker rat and markedly reduced by dietary lipophilic antioxidants and depressed by dietary tiron.Vasodepression to bolus does GTN (0.1–100 μg kg−1 i.v.), but not endothelium-dependent vasodepression to bolus dose acetylcholine (ACh, 0.02–2.0 μg kg−1 i.v.), was impaired in obese animals and completely restored by dietary antioxidants.Nitrate tolerance developed in vivo during a 1 h infusion of GTN (40 μg kg−1 min−1 i.v.) appeared more severe in obese animals. However, rapid nitrate tolerance was not affected by dietary antioxidants in either the obese or lean Zucker rat.We therefore provide evidence that elevated oxidant stress in the obese Zucker rat is associated with an impairment in nitrate vasodepressor activity. However, our data are not consistent with either a role for oxidant stress in rapid nitrate tolerance development in the anaesthetized Zucker rat or the aggravation of this tolerance by pre-existing oxidant stress. PMID:9831930

  12. Glyceryl trinitrate and caprylic acid for the mitigation of the Desulfovibrio vulgaris biofilm on C1018 carbon steel.

    PubMed

    Li, Y; Zhang, P; Cai, W; Rosenblatt, J S; Raad, I I; Xu, D; Gu, T

    2016-02-01

    Microbiologically influenced corrosion (MIC), also known as biocorrosion, is caused by corrosive biofilms. MIC is a growing problem, especially in the oil and gas industry. Among various corrosive microbes, sulfate reducing bacteria (SRB) are often the leading culprit. Biofilm mitigation is the key to MIC mitigation. Biocide applications against biofilms promote resistance over time. Thus, it is imperative to develop new biodegradable and cost-effective biocides for large-scale field applications. Using the corrosive Desulfovibrio vulgaris (an SRB) biofilm as a model biofilm, this work demonstrated that a cocktail of glyceryl trinitrate (GTN) and caprylic acid (CA) was very effective for biofilm prevention and mitigation of established biofilms on C1018 carbon steel coupons. The most probable number sessile cell count data and confocal laser scanning microscope biofilm images proved that the biocide cocktail of 25 ppm (w/w) GTN + 0.1% (w/w) CA successfully prevented the D. vulgaris biofilm establishment on C1018 carbon steel coupons while 100 ppm GTN + 0.1% CA effectively mitigated pre-established D. vulgaris biofilms on C1018 carbon steel coupons. In both cases, the cocktails were able to reduce the sessile cell count from 10(6) cells/cm(2) to an undetectable level.

  13. Haemodynamic effects of glyceryl trinitrate following repeated application of a transdermal delivery system with a phasic release profile.

    PubMed

    Wiegand, A; Bonn, R; Wagner, F; Trenk, D; Jähnchen, E

    1991-01-01

    The haemodynamic effects and plasma concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites were investigated in 8 healthy male volunteers during 5 days of application of a new transdermal delivery system (TDS) with time-dependent release characteristics, which were considered to prevent or to diminish development of nitrate tolerance. On the first and fifth day of administration the following haemodynamic parameters were determined: digital pulse ratio of height of systolic peak to height of dicrotic wave (i.e. a/b-ratio), heart rate and systolic blood pressure under orthostatic conditions. Peak plasma concentrations of GTN were 139 and 155 pg.ml-1 on the first and fifth day of treatment, and the corresponding trough concentrations (i.e. 24 h after administration) were 52.5 and 36.6 pg.ml-1, respectively. Compared to placebo, the area under the effect curve of the a/b-ratio of the digital pulse was increased on the first (25.6%) and fifth day (13%). A significant increase of heart rate and a decrease of systolic blood pressure were seen only on the first day of treatment. The haemodynamic effects of sublingual GTN 0.8 mg were reduced by 69% (a/b-ratio) and 52% (standing heart rate) on the fifth day compared to the pretreatment values. Thus, the phasic release of GTN from the new TDS can be demonstrated by the time course of the plasma concentrations of GTN and its metabolites. Nevertheless, following repeated administration the hemodynamic effects are blunted.

  14. Glyceryl trinitrate for the treatment of preterm labor

    PubMed Central

    Çalışkan, Şafak; Narin, Mehmet Ali; Dede, Faruk Suat; Narin, Raziye; Dede, Hülya; Kandemir, Ömer

    2015-01-01

    Objective This study was conducted to compare the tocolytic efficacy of glyceryltrinitrate (GTN) with that of magnesium sulfate (MgSO4) and to investigate serum nitric oxide metabolites before and after tocolysis. Material and Methods In total, 48 women between 27 and 34 weeks’ gestation with threatened preterm labor and intact membranes were randomly allocated to receive either GTN or MgSO4 tocolysis. Main outcome measures included tocolytic efficacy and maternal side effect(s) of the tocolytic agent. Obstetric and neonatal outcomes as well as pretreatment and posttreatment nitric oxide (NO) metabolites were assessed. Results Forty-one patients were included into the final analysis. Uterine contraction cessation times were 3.66±1.28 and 6.83±3.47 hours for GTN and MgSO4 groups, respectively. Similarly, maternal side effects were significantly lower in the GTN group than in the MgSO4 group, and no serious maternal side effects were recorded. Serum NO metabolite levels before treatment were significantly lower in the treatment groups than in the controls. Serum nitrite levels were significantly increased after tocolytic treatment both in MgSO4 and GTN groups. Conclusion GTN effectively delays preterm delivery and reduces neonatal morbidity and mortality with less maternal side effects and seems to be an effective and safe alternative to MgSO4. PMID:26401112

  15. 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

    PubMed Central

    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

    2016-01-01

    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

  16. Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate.

    PubMed Central

    Culling, W; Singh, H; Bashir, A; Griffiths, B E; Dalal, J J; Sheridan, D J

    1984-01-01

    We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN. PMID:6422972

  17. 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.

    PubMed

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

    2011-05-01

    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.

  18. Biodegradation of Glycerol Trinitrate and Pentaerythritol Tetranitrate by Agrobacterium radiobacter

    PubMed Central

    White, G. F.; Snape, J. R.; Nicklin, S.

    1996-01-01

    Bacteria capable of metabolizing highly explosive and vasodilatory glycerol trinitrate (GTN) were isolated under aerobic and nitrogen-limiting conditions from soil, river water, and activated sewage sludge. One of these strains (from sewage sludge) chosen for further study was identified as Agrobacterium radiobacter subgroup B. A combination of high-pressure liquid chromatography and nuclear magnetic resonance analyses of the culture medium during the growth of A. radiobacter on basal salts-glycerol-GTN medium showed the sequential conversion of GTN to glycerol dinitrates and glycerol mononitrates. Isomeric glycerol 1,2-dinitrate and glycerol 1,3-dinitrate were produced simultaneously and concomitantly with the disappearance of GTN, with significant regioselectivity for the production of the 1,3-dinitrate. Dinitrates were further degraded to glycerol 1- and 2-mononitrates, but mononitrates were not biodegraded. Cells were also capable of metabolizing pentaerythritol tetranitrate, probably to its trinitrate and dinitrate analogs. Extracts of broth-grown cells contained an enzyme which in the presence of added NADH converted GTN stoichiometrically to nitrite and the mixture of glycerol dinitrates. The specific activity of this enzyme was increased 160-fold by growth on GTN as the sole source of nitrogen. PMID:16535244

  19. 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.

    PubMed

    2004-01-01

    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

  20. 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.

    PubMed

    2007-01-01

    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

  1. Denitration of glycerol trinitrate by resting cells and cell extracts of Bacillus thuringiensis/cereus and Enterobacter agglomerans.

    PubMed Central

    Meng, M; Sun, W Q; Geelhaar, L A; Kumar, G; Patel, A R; Payne, G F; Speedie, M K; Stacy, J R

    1995-01-01

    A number of microorganisms were selected from soil and sediment samples which were known to have been previously exposed to nitrate ester contaminants. The two most effective bacteria for transforming glycerol trinitrate (GTN) were identified as Bacillus thuringiensis/cereus and Enterobacter agglomerans. For both isolates, denitration activities were expressed constitutively and GTN was not required for induction. Dialysis of cell extracts from both isolates did not affect denitration, which indicates that dissociable and depletable cofactors are not required for denitration. With thin-layer chromatography and high-performance liquid chromatography, the denitration pathway for both isolates was shown to be a sequential denitration of GTN to glycerol dinitrate isomers, glycerol mononitrate isomers, and ultimately to glycerol. GTN was observed to be completely converted to glycerol during a long-term incubation of cell extracts. PMID:7618866

  2. Denitration of glycerol trinitrate by resting cells and cell extracts of Bacillus thuringiensis/cereus and Enterobacter agglomerans.

    PubMed

    Meng, M; Sun, W Q; Geelhaar, L A; Kumar, G; Patel, A R; Payne, G F; Speedie, M K; Stacy, J R

    1995-07-01

    A number of microorganisms were selected from soil and sediment samples which were known to have been previously exposed to nitrate ester contaminants. The two most effective bacteria for transforming glycerol trinitrate (GTN) were identified as Bacillus thuringiensis/cereus and Enterobacter agglomerans. For both isolates, denitration activities were expressed constitutively and GTN was not required for induction. Dialysis of cell extracts from both isolates did not affect denitration, which indicates that dissociable and depletable cofactors are not required for denitration. With thin-layer chromatography and high-performance liquid chromatography, the denitration pathway for both isolates was shown to be a sequential denitration of GTN to glycerol dinitrate isomers, glycerol mononitrate isomers, and ultimately to glycerol. GTN was observed to be completely converted to glycerol during a long-term incubation of cell extracts.

  3. Purification, properties, and sequence of glycerol trinitrate reductase from Agrobacterium radiobacter.

    PubMed Central

    Snape, J R; Walkley, N A; Morby, A P; Nicklin, S; White, G F

    1997-01-01

    Glycerol trinitrate (GTN) reductase, which enables Agrobacterium radiobacter to utilize GTN and related explosives as sources of nitrogen for growth, was purified and characterized, and its gene was cloned and sequenced. The enzyme was a 39-kDa monomeric protein which catalyzed the NADH-dependent reductive scission of GTN (Km = 23 microM) to glycerol dinitrates (mainly the 1,3-isomer) with a pH optimum of 6.5, a temperature optimum of 35 degrees C, and no dependence on metal ions for activity. It was also active on pentaerythritol tetranitrate (PETN), on isosorbide dinitrate, and, very weakly, on ethyleneglycol dinitrate, but it was inactive on isopropyl nitrate, hexahydro-1,3,5-trinitro-1,3,5-triazine, 2,4,6-trinitrotoluene, ammonium ions, nitrate, or nitrite. The amino acid sequence deduced from the DNA sequence was homologous (42 to 51% identity and 61 to 69% similarity) to those of PETN reductase from Enterobacter cloacae, N-ethylmaleimide reductase from Escherichia coli, morphinone reductase from Pseudomonas putida, and old yellow enzyme from Saccharomyces cerevisiae, placing the GTN reductase in the alpha/beta barrel flavoprotein group of proteins. GTN reductase and PETN reductase were very similar in many respects except in their distinct preferences for NADH and NADPH cofactors, respectively. PMID:9401040

  4. Old yellow enzyme: Reduction of nitrate esters, glycerin trinitrate, and propylene 1,2-dinitrate

    PubMed Central

    Meah, Younus; Brown, Bette Jo; Chakraborty, Sumita; Massey, Vincent

    2001-01-01

    The reaction of the old yellow enzyme and reduced flavins with organic nitrate esters has been studied. Reduced flavins have been found to react readily with glycerin trinitrate (GTN ) (nitroglycerin) and propylene dinitrate, with rate constants at pH 7.0, 25°C of 145 M−1s−1 and 5.8 M−1s−1, respectively. With GTN, the secondary nitrate was removed reductively 6 times faster than the primary nitrate, with liberation of nitrite. With propylene dinitrate, on the other hand, the primary nitrate residue was 3 times more reactive than the secondary residue. In the old yellow enzyme-catalyzed NADPH-dependent reduction of GTN and propylene dinitrate, ping-pong kinetics are displayed, as found for all other substrates of the enzyme. Rapid-reaction studies of mixing reduced enzyme with the nitrate esters show that a reduced enzyme–substrate complex is formed before oxidation of the reduced flavin. The rate constants for these reactions and the apparent Kd values of the enzyme–substrate complexes have been determined and reveal that the rate-limiting step in catalysis is reduction of the enzyme by NADPH. Analysis of the products reveal that with the enzyme-catalyzed reactions, reduction of the primary nitrate in both GTN and propylene dinitrate is favored by comparison with the free-flavin reactions. This preferential positional reactivity can be rationalized by modeling of the substrates into the known crystal structure of the enzyme. In contrast to the facile reaction of free reduced flavins with GTN, reduced 5-deazaflavins have been found to react some 4–5 orders of magnitude slower. This finding implies that the chemical mechanism of the reaction is one involving radical transfers. PMID:11438708

  5. Dermal Sensitization Potential of Trimethylolethane Trinitrate (TMETN) in Guinea Pigs

    DTIC Science & Technology

    1989-07-01

    27 LeTellier et a/.-15 Appendix A: CHEMICAL DATA Chemical Name: 1,3- Propanediol , 2-methyl-2[(nitrooxy)methyl]-dinitrate (ester) Other...Names: 1,3- Propanediol -2-(hydroxymethyl)-2-methyl-, trinitrate; 1,1,1-Trimethylolethane trinitrate(TMETN), Metriol trinitrate (MTN); Nitropentaglycerin

  6. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Listing of Specific Substances Affirmed as GRAS § 184.1324 Glyceryl monostearate. (a) Glyceryl... esters of fatty acids present in commercial stearic acid. Glyceryl monostearate is prepared by..., of stearic acid that is derived from edible sources. (b) The ingredient must be of a purity...

  7. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Listing of Specific Substances Affirmed as GRAS § 184.1324 Glyceryl monostearate. (a) Glyceryl... esters of fatty acids present in commercial stearic acid. Glyceryl monostearate is prepared by..., of stearic acid that is derived from edible sources. (b) The ingredient must be of a purity...

  8. Acute Oral Toxicity of Trimethylolethane Trinitrate (TMETN) in ICR Mice

    DTIC Science & Technology

    1989-07-01

    56 Brown et al.--16 Appendix A: CHEMICAL DATA Chemical Name: 1,3- Propanediol , 2-methyl-2 [(nitroxy)methyl]-dinitrate (ester) Other Names: 1,3... Propanediol -2-(hydroxymethyl)-2-methyl-, trinitrate; 1,1,1-trimethylolethane trinitrate (TMETN), metriol trinitrate (MTN); nitropentaglycerin Lot Number: 53...0.5 0.6 Brown et al.--56 Appendix G: PATHOLOGY REPORT Oral Lethal Dose (MLD) Test in Mice of 1, 3 - Propanediol , 2-(hydroxymethyl)-2-methyl

  9. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.811 Glyceryl tristearate. The food additive glyceryl tristearate may be safely used in food in accordance with the following prescribed conditions: (a) The food additive (CAS Reg....

  10. 21 CFR 184.1323 - Glyceryl monooleate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... prepared by esterification of commerical oleic acid that is derived either from edible sources or from tall oil fatty acids meeting the requirements of § 172.862 of this chapter. It contains glyceryl...

  11. 21 CFR 184.1323 - Glyceryl monooleate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... prepared by esterification of commerical oleic acid that is derived either from edible sources or from tall oil fatty acids meeting the requirements of § 172.862 of this chapter. It contains glyceryl...

  12. 21 CFR 184.1323 - Glyceryl monooleate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... prepared by esterification of commerical oleic acid that is derived either from edible sources or from tall oil fatty acids meeting the requirements of § 172.862 of this chapter. It contains glyceryl...

  13. 21 CFR 184.1323 - Glyceryl monooleate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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)...

  14. 21 CFR 184.1323 - Glyceryl monooleate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... commerical oleic acid that is derived either from edible sources or from tall oil fatty acids meeting the...) and glyceryl esters of fatty acids present in commercial oleic acid. (b) The ingredient must be of...

  15. Acute Oral Toxicity of Trimethylolethane Trinitrate (TMETN) in Sprague- Dawley Rats

    DTIC Science & Technology

    1989-07-01

    61 LeTellier et al.--16 Appendix A: CHEMICAL DATA Chemical Name: 1,3- Propanediol , 2-methyl-2 [(nitroxy)methyl]-dinitrate (ester) Other Names: 1,3... Propanediol -2-(hydroxymethyl)-2-methyl-, trinitrate; 1,1,1-trimethylolethane trinitrate (TMETN), metriol trinitrate (MTN); nitropentaglycerin Lot... Propanediol , 2-(hydroxymethyl)- 2-methyl -, trinitrate (TMETN). Species: Rat Strain: Sprague-Dawley. History: See LAIR SOP-OP-STX-36. Animals that

  16. 21 CFR 184.1329 - Glyceryl palmitostearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy metals (as lead): Not more than... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glyceryl palmitostearate. 184.1329 Section 184.1329 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  17. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Iodine number. Not more than 3. (6) Heavy metals (as Pb). Not more than 10 parts per million. (c) In... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glyceryl behenate. 184.1328 Section 184.1328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  18. 21 CFR 184.1329 - Glyceryl palmitostearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... substance is a mixture of mono-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy metals... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glyceryl palmitostearate. 184.1329 Section 184.1329 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  19. 21 CFR 184.1329 - Glyceryl palmitostearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... substance is a mixture of mono-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy metals... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glyceryl palmitostearate. 184.1329 Section 184.1329 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  20. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Iodine number. Not more than 3. (6) Heavy metals (as Pb). Not more than 10 parts per million. (c) In... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glyceryl behenate. 184.1328 Section 184.1328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  1. 21 CFR 184.1329 - Glyceryl palmitostearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... substance is a mixture of mono-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy metals... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glyceryl palmitostearate. 184.1329 Section 184.1329 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  2. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Iodine number. Not more than 3. (6) Heavy metals (as Pb). Not more than 10 parts per million. (c) In... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glyceryl behenate. 184.1328 Section 184.1328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  3. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Iodine number. Not more than 3. (6) Heavy metals (as Pb). Not more than 10 parts per million. (c) In... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Glyceryl behenate. 184.1328 Section 184.1328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...

  4. 21 CFR 184.1329 - Glyceryl palmitostearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... substance is a mixture of mono-, di-, and triglycerides of palmitic acid and stearic acid. (2) Heavy metals... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Glyceryl palmitostearate. 184.1329 Section 184.1329 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  5. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Heavy metals (as Pb). Not more than 10 parts per million. (c) In accordance with § 184.1(b)(1) of this... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glyceryl behenate. 184.1328 Section 184.1328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  6. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  7. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false 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...

  8. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false 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...

  9. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false 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...

  10. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glyceryl-lacto esters of fatty acids. 172.852... § 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 accordance with the following...

  11. High School Observations of AGN Using the GTN

    NASA Astrophysics Data System (ADS)

    McLin, Kevin M.; Jordan, R.; Perkins, A.; Adkins, J.; Cominsky, L.

    2008-03-01

    Students at Deer Valley High School in Antioch, California have undertaken an AGN monitoring program using telescopes of the Global Telescope Network (GTN) and SkyNet. The GTN is a network of small telescopes funded by GLAST to support the science of high energy astrophysics missions, specifically GLAST, Swift and XMM-Newton. It is managed by the NASA E/PO Group at Sonoma State University. SkyNet is a network of small telescopes managed from the University of North Carolina to catch gamma ray burst afterglows. A primary motivator behind both networks is education. In the program outlined here, high school students will schedule, reduce and analyze observations of active galaxies in order to determine if any microflaring activity has occurred. Students will compare their results with previous studies reported in the literature and then report their own results at the Contra Costa County Science and Engineering Fair. This work will give the students direct experience with several aspects of scientific research, including literature searches, data acquisition and analysis, and reporting of results.

  12. Formation of the NO donors glyceryl mononitrate and glyceryl mononitrite from the reaction of peroxynitrite with glycerol.

    PubMed

    White, C R; Moellering, D; Patel, R P; Kirk, M; Barnes, S; Darley-Usmar, V M

    1997-12-01

    Peroxynitrite (ONOO-), formed from the rapid reaction of superoxide (O2-.) with NO, is known to generate stable compounds capable of donating NO on reaction with thiols and molecules containing hydroxy groups. Using glycerol as a model compound for the reactions of ONOO- with biomolecules containing hydroxy groups, we separated the products and identified them by HPLC/MS. It was shown that both glyceryl mononitrate and glyceryl mononitrite were formed and released NO on incubation with copper and l-cysteine. The compounds were stable over a period of 4h when shielded from light and kept on ice. Slow spontaneous decomposition occurred in the buffer used for the bioassay, but this was not sufficient to explain the vasorelaxing properties of these NO donors. It is concluded that the stable organic nitrate and nitrite have the capacity to be metabolized by vascular tissues, resulting in vasorelaxation.

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

    PubMed

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

    2016-04-15

    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).

  14. Serelaxin Treatment Reduces Oxidative Stress and Increases Aldehyde Dehydrogenase-2 to Attenuate Nitrate Tolerance

    PubMed Central

    Leo, Chen Huei; Fernando, Dhanushke T.; Tran, Lillie; Ng, Hooi Hooi; Marshall, Sarah A.; Parry, Laura J.

    2017-01-01

    Background: Glyceryl trinitrate (GTN) is a commonly prescribed treatment for acute heart failure patients. However, prolonged GTN treatment induces tolerance, largely due to increased oxidative stress and reduced aldehyde dehydrogenase-2 (ALDH-2) expression. Serelaxin has several vasoprotective properties, which include reducing oxidative stress and augmenting endothelial function. We therefore tested the hypothesis in rodents that serelaxin treatment could attenuate low-dose GTN-induced tolerance. Methods and Results: Co-incubation of mouse aortic rings ex vivo with GTN (10 μM) and serelaxin (10 nM) for 1 h, restored GTN responses, suggesting that serelaxin prevented the development of GTN tolerance. Male Wistar rats were subcutaneously infused with ethanol (control), low-dose GTN+placebo or low-dose GTN+serelaxin via osmotic minipumps for 3 days. Aortic vascular function and superoxide levels were assessed using wire myography and lucigenin-enhanced chemiluminescence assay respectively. Changes in aortic ALDH-2 expression were measured by qPCR and Western blot respectively. GTN+placebo infusion significantly increased superoxide levels, decreased ALDH-2 and attenuated GTN-mediated vascular relaxation. Serelaxin co-treatment with GTN significantly enhanced GTN-mediated vascular relaxation, reduced superoxide levels and increased ALDH-2 expression compared to GTN+placebo-treated rats. Conclusion: Our data demonstrate that a combination of serelaxin treatment with low dose GTN attenuates the development of GTN-induced tolerance by reducing superoxide production and increasing ALDH-2 expression in the rat aorta. We suggest that serelaxin may improve nitrate efficacy in a clinical setting. PMID:28377719

  15. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (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...

  16. Nitric oxide signaling pathway activation inhibits the immune escape of pancreatic carcinoma cells

    PubMed Central

    LU, YEBIN; HU, JUANJUAN; SUN, WEIJIA; DUAN, XIAOHUI; CHEN, XIONG

    2014-01-01

    The aim of the present study was to investigate the effect of the nitric oxide signaling pathway on immune escape; thus, a tumorigenesis model was established using nude mice. The mice were inoculated with pancreatic carcinoma cells and divided into two groups, a glyceryl trinitrate (GTN) and a placebo group. When tumor volumes reached 150 mm3, the mice in the GTN group were treated with GTN transdermal patches (dose, 7.3 μg/h) while the mice in the placebo group were administered untreated patches. Following treatment, the tumor volume was recorded every 3–4 days and after 28 days, the tumors were analyzed. The results indicated that GTN treatment may reduce the levels of soluble major histocompatibility complex class I chain-related molecules, and natural killer group 2 member D, as well as inhibiting tumor growth. PMID:25364398

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

    PubMed

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

    2009-01-01

    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.

  18. Synthesis, chiral HPLC resolution and configuration assignment of 1-phenylglyceryl trinitrate stereomers.

    PubMed

    Chegaev, Konstantin; Lazzarato, Loretta; Tron, Gian Cesare; Marabello, Domenica; Stilo, Antonella Di; Cena, Clara; Fruttero, Roberta; Gasco, Alberto; Vanthuyne, Nicolas; Roussel, Christian

    2006-06-01

    As an introductory study of in vitro vasodilating activity, the access to the four stereomers of 1-phenylglyceryl trinitrate is described using achiral and chiral chromatography. For semi-preparative separation of the enantiomers, a Chiralcel OD (250 x 10 mm, 10 microm) was used. Catalytic reduction leading to the corresponding stereomers of 1-phenylglycerol allowed absolute configuration assignments. The same methods were used for the separation and configuration assignment of the enantiomers of 3-phenylpropane-1,2-diyl dinitrate.

  19. Numerical study of electron beam welded butt joints with the GTN model

    NASA Astrophysics Data System (ADS)

    Tu, Haoyun; Schmauder, Siegfried; Weber, Ulrich

    2012-08-01

    The fracture behavior of S355NL electron beam welded steel joints is investigated experimentally and numerically. The simulation of crack propagation in an electron beam welded steel joint was performed with the Gurson-Tvergaard-Needleman (GTN) damage model. A parameter study of the GTN model was adopted which reveals the influence of parameters on the material behavior of notched round and compact tension specimens. Based on the combined method of metallographic investigations and numerical calibration, the GTN parameters were fixed. The same parameters were used to predict the ductile fracture of compact tension specimens with the initial crack located at different locations. Good match can be found between the numerical and experimental results in the form of force versus Crack Opening Displacement as well as fracture resistance curves.

  20. The new database of the Global Terrestrial Network for Permafrost (GTN-P)

    NASA Astrophysics Data System (ADS)

    Biskaborn, B. K.; Lanckman, J.-P.; Lantuit, H.; Elger, K.; Streletskiy, D. A.; Cable, W. L.; Romanovsky, V. E.

    2015-09-01

    The Global Terrestrial Network for Permafrost (GTN-P) provides the first dynamic database associated with the Thermal State of Permafrost (TSP) and the Circumpolar Active Layer Monitoring (CALM) programs, which extensively collect permafrost temperature and active layer thickness (ALT) data from Arctic, Antarctic and mountain permafrost regions. The purpose of GTN-P is to establish an early warning system for the consequences of climate change in permafrost regions and to provide standardized thermal permafrost data to global models. In this paper we introduce the GTN-P database and perform statistical analysis of the GTN-P metadata to identify and quantify the spatial gaps in the site distribution in relation to climate-effective environmental parameters. We describe the concept and structure of the data management system in regard to user operability, data transfer and data policy. We outline data sources and data processing including quality control strategies based on national correspondents. Assessment of the metadata and data quality reveals 63 % metadata completeness at active layer sites and 50 % metadata completeness for boreholes. Voronoi tessellation analysis on the spatial sample distribution of boreholes and active layer measurement sites quantifies the distribution inhomogeneity and provides a potential method to locate additional permafrost research sites by improving the representativeness of thermal monitoring across areas underlain by permafrost. The depth distribution of the boreholes reveals that 73 % are shallower than 25 m and 27 % are deeper, reaching a maximum of 1 km depth. Comparison of the GTN-P site distribution with permafrost zones, soil organic carbon contents and vegetation types exhibits different local to regional monitoring situations, which are illustrated with maps. Preferential slope orientation at the sites most likely causes a bias in the temperature monitoring and should be taken into account when using the data for global

  1. The GTN-P Data Management System: A central database for permafrost monitoring parameters of the Global Terrestrial Network for Permafrost (GTN-P) and beyond

    NASA Astrophysics Data System (ADS)

    Lanckman, Jean-Pierre; Elger, Kirsten; Karlsson, Ævar Karl; Johannsson, Halldór; Lantuit, Hugues

    2013-04-01

    Permafrost is a direct indicator of climate change and has been identified as Essential Climate Variable (ECV) by the global observing community. The monitoring of permafrost temperatures, active-layer thicknesses and other parameters has been performed for several decades already, but it was brought together within the Global Terrestrial Network for Permafrost (GTN-P) in the 1990's only, including the development of measurement protocols to provide standardized data. GTN-P is the primary international observing network for permafrost sponsored by the Global Climate Observing System (GCOS) and the Global Terrestrial Observing System (GTOS), and managed by the International Permafrost Association (IPA). All GTN-P data was outfitted with an "open data policy" with free data access via the World Wide Web. The existing data, however, is far from being homogeneous: it is not yet optimized for databases, there is no framework for data reporting or archival and data documentation is incomplete. As a result, and despite the utmost relevance of permafrost in the Earth's climate system, the data has not been used by as many researchers as intended by the initiators of the programs. While the monitoring of many other ECVs has been tackled by organized international networks (e.g. FLUXNET), there is still no central database for all permafrost-related parameters. The European Union project PAGE21 created opportunities to develop this central database for permafrost monitoring parameters of GTN-P during the duration of the project and beyond. The database aims to be the one location where the researcher can find data, metadata, and information of all relevant parameters for a specific site. Each component of the Data Management System (DMS), including parameters, data levels and metadata formats were developed in cooperation with the GTN-P and the IPA. The general framework of the GTN-P DMS is based on an object oriented model (OOM), open for as many parameters as possible, and

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

    PubMed

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

    2016-11-03

    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.

  3. STUDY OF DUAL MATRIX TABLETS CONTAINING HYPROMELLOSE OF DIFFERENT VISCOSITY DEGREE AND GLYCERYL DIBEHENATE.

    PubMed

    Mužíková, Jitka; Holubová, Katerina; Komersová, Alena; Lochar, Václav

    2016-01-01

    Studies are described on the compressibility of directly compressible tableting materials containing two viscosity types of hypromellose in two concentrations and tableting materials containing additional glyceryl dibehenate, also in two concentrations. Compressibility is evaluated by means of the energy profile of the compression process and determination of tensile strength of tablets. Dissolution test examines the rate of release of the active ingredient from matrix tablets, which is subsequently evaluated mathematically. Increased concentrations of both hypromelloses and an addition of glyceryl dibehenate into tablets with both types of hypromellose improved compressibility. The rate of drug release was decreased with increasing viscosity degree of hypromellose and its increasing concentration. An addition of glyceryl dibehenate exerted the same influence on release as increased concentrations of the pertinent hypromellose.

  4. Failure analysis of AZ31 magnesium alloy sheets based on the extended GTN damage model

    NASA Astrophysics Data System (ADS)

    Wang, Rui-ze; Chen, Zhang-hua; Li, Yu-jie; Dong, Chao-fang

    2013-12-01

    Based on the Gurson-Tvergaard-Needleman (GTN) model and Hill's quadratic anisotropic yield criterion, a combined experimental-numerical study on fracture initiation in the process of thermal stamping of Mg alloy AZ31 sheets was carried out. The aim is to predict the formability of thermal stamping of the Mg alloy sheets at different temperatures. The presented theoretical framework was implemented into a VUMAT subroutine for ABAQUS/EXPLICIT. Internal damage evolution due to void growth and coalescence developed at different temperatures in the Mg alloy sheets was observed by scanning electron microscopy (SEM). Moreover, the thermal effects on the void growth, coalescence, and fracture behavior of the Mg alloy sheets were analyzed by the extended GTN model and forming limit diagrams (FLD). Parameters employed in the GTN model were determined from tensile tests and numerical iterative computation. The distribution of major and minor principal strains in the specimens was determined from the numerical results. Therefore, the corresponding forming limit diagrams at different stress levels and temperatures were drawn. The comparison between the predicted forming limits and the experimental data shows a good agreement.

  5. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glyceryl tri-(12-acetoxy-stearate). 178.3505 Section 178.3505 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants...

  6. Water quantitatively induces the mucoadhesion of liquid crystalline phases of glyceryl monooleate.

    PubMed

    Lee, J; Young, S A; Kellaway, I W

    2001-05-01

    The possible role of water in the mucoadhesion phenomenon exhibited by the liquid crystalline phases of glyceryl monooleate was investigated using an in-vitro tensile strength technique. The mucoadhesion of the liquid crystalline phases of glyceryl monooleate was found to occur following uptake of water. The mucoadhesive force of the cubic phase was consistent since it is not capable of taking up additional water. An increase in pre-load period greatly facilitated the mucoadhesion of glyceryl monooleate (0% w/w initial water content), suggesting that the mucoadhesion is dependent upon the extent of the dehydration of the substrate. A good linear relationship between initial water content of the liquid crystalline phases and mucoadhesive force led to the conclusion that the mucoadhesive force increased with decreasing initial water concentration. Rheological properties of the liquid crystalline phases were also studied to allow a correlation between physical changes and mucoadhesion of the liquid crystalline phases, revealing that higher water concentrations in the liquid crystalline phases led to a more ordered structure that showed less mucoadhesion. The results of this study indicated that the mucoadhesive force of the liquid crystalline phases of glyceryl monooleate is determined by the capability to take up water from a water-rich environment. It may, therefore, be advantageous to use the lamellar phase as a buccal drug carrier as opposed to the relatively less mucoadhesive cubic phase.

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

    PubMed

    Johnson, W

    2001-01-01

    Triesters of glycerin and aliphatic acids, known generically as glyceryl triesters and specifically as Trilaurin, etc., are used in cosmetic products as occlusive skin-conditioning agents and/or nonaqueous viscosity-increasing agents. Hundreds of glyceryl triesters are used in a wide variety of cosmetic products at concentrations ranging from a few tenths of a percent to 46%. Glyceryl triesters are also known as triglycerides; ingested triglycerides are metabolized to monoglycerides, free fatty acids, and glycerol, all of which are absorbed in the intestinal mucosa and undergo further metabolism. Dermal absorption of Triolein in mice was nil; the oil remained at the application site. Only slight absorption was seen in guinea pig skin. Tricaprylin and other glyceryl triesters have been shown to increase the skin penetration of drugs. Little or no acute, subchronic, or chronic oral toxicity was seen in animal studies unless levels approached a significant percentage of caloric intake. Subcutaneous injections of Tricaprylin in rats over a period of 5 weeks caused a granulomatous reaction characterized by oil deposits surrounded by macrophages. Dermal application was not associated with significant irritation in rabbit skin. Ocular exposures were, at most, mildly irritating to rabbit eyes. No evidence of sensitization or photosensitization was seen in a guinea pig maximization test. Most of the genotoxicity test systems were negative. Tricaprylin, Trioctanoin, and Triolein have historically been used as vehicles in carcinogenicity testing of other chemicals. In one study, subcutaneous injection of Tricaprylin in newborn mice produced more tumors in lymphoid tissue than were seen in untreated animals, whereas neither subcutaneous or intraperitoneal injection in 4- to 6-week-old female mice produced any tumors in another study. Trioctanoin injected subcutaneously in hamsters produced no tumors. Trioctanoin injected intraperitoneally in pregnant rats was associated with

  8. Reversion of nitrate tolerance in rat aorta rings by freeze-dried red wine.

    PubMed

    Fusi, Fabio; Sgaragli, Giampietro

    2015-04-01

    Chronically administered organic nitrates induce nitrate tolerance and endothelial dysfunction, which limit their therapeutic use. eNOS uncoupling, ROS over-production, aldehyde dehydrogenase-2 as well as superoxide dismutase (SOD) oxidative inhibition, and cGMP desensitization are thought to play an important role. Natural polyphenols are effective antioxidants, which might counteract the mechanisms leading to nitrate tolerance. The aim of this work was to verify whether freeze-dried (dealcoholized) red wine (FDRW) was able to revert glyceryl trinitrate (GTN) tolerance and endothelial dysfunction induced in rat aorta rings with either GTN or diethyldithiocarbamate (DETCA), an irreversible inhibitor of Cu/Zn SOD. GTN induced a concentration-dependent relaxation of rings pre-contracted with phenylephrine. GTN spasmolysis was significantly reduced in rings pre-incubated with either GTN or DETCA. FDRW, at 2.8 µg of gallic acid equivalents (GAE)/mL concentration, was able to revert partially, though significantly, GTN-induced tolerance but not tolerance and endothelial dysfunction induced by DETCA. This work provides the first evidence in vitro that red wine components, at concentrations comparable to those achieved in human blood after moderate consumption of red wine, revert tolerance to nitrates with a mechanism possibly mediated by SOD.

  9. The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles.

    PubMed

    Mayer, B; Beretta, M

    2008-09-01

    Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3-electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies.

  10. The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles

    PubMed Central

    Mayer, B; Beretta, M

    2008-01-01

    Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3-electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies. PMID:18574453

  11. Integration of glacier databases within the Global Terrestrial Network for Glaciers (GTN-G)

    NASA Astrophysics Data System (ADS)

    Zemp, M.; Raup, B. H.; Armstrong, R.; Ballagh, L.; Gärtner-Roer, I.; Haeberli, W.; Hoelzle, M.; Kääb, A.; Kargel, J.; Paul, F.

    2009-04-01

    Changes in glaciers and ice caps provide some of the clearest evidence of climate change and have impacts on global sea level fluctuations, regional hydrological cycles and local natural hazard situations. Internationally coordinated collection and distribution of standardized information about glaciers and ice caps was initiated in 1894 and is today coordinated within the Global Terrestrial Network for Glaciers (GTN-G). A recently established GTN-G Steering Committee coordinates, supports and advices the operational bodies responsible for the international glacier monitoring, which are the World Glacier Monitoring Service (WGMS), the US National Snow and Ice Data Center (NSIDC) and the Global Land Ice Measurements from Space (GLIMS) initiative. In this presentation, we provide an overview of (i) the integration of the various operational databases, (ii) the development of a one-stop web-interface to these databases, and (iii) the available datasets. By joint efforts consistency and interoperability of the different glacier databases is elaborated. Thereby, the lack of a complete worldwide, detailed glacier inventory as well as different historical developments and methodological contexts of the datasets are major challenges for linking individual glaciers throughout the databases. A map-based web-interface, implemented based on OpenLayer 2.0 and Web Map/Feature Services, is elaborated to spatially link the available data and to provide data users a fast overview of all available data. With this new online service, GTN-G provides fast access to information on glacier inventory data from 100,000 glaciers mainly based on aerial photographs and from 80,000 glaciers mainly based on satellite images, length change series from 1,800 glaciers, mass balance series from 230 glaciers, special events (e.g., hazards, surges, calving instabilities) from 130 glaciers, as well as 10,000 photographs from some 470 glaciers.

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

    PubMed

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

    2009-08-01

    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.

  13. Numerical Simulation of Tension Properties for Al-Cu Alloy Friction Stir-Welded Joints with GTN Damage Model

    NASA Astrophysics Data System (ADS)

    Sun, Guo-Qin; Sun, Feng-Yang; Cao, Fang-Li; Chen, Shu-Jun; Barkey, Mark E.

    2015-11-01

    The numerical simulation of tensile fracture behavior on Al-Cu alloy friction stir-welded joint was performed with the Gurson-Tvergaard-Needleman (GTN) damage model. The parameters of the GTN model were studied in each region of the friction stir-welded joint by means of inverse identification. Based on the obtained parameters, the finite element model of the welded joint was built to predict the fracture behavior and tension properties. Good agreement can be found between the numerical and experimental results in the location of the tensile fracture and the mechanical properties.

  14. A central database for the Global Terrestrial Network for Permafrost (GTN-P)

    NASA Astrophysics Data System (ADS)

    Elger, Kirsten; Lanckman, Jean-Pierre; Lantuit, Hugues; Karlsson, Ævar Karl; Johannsson, Halldór

    2013-04-01

    The Global Terrestrial Network for Permafrost (GTN-P) is the primary international observing network for permafrost sponsored by the Global Climate Observing System (GCOS) and the Global Terrestrial Observing System (GTOS), and managed by the International Permafrost Association (IPA). It monitors the Essential Climate Variable (ECV) permafrost that consists of permafrost temperature and active-layer thickness, with the long-term goal of obtaining a comprehensive view of the spatial structure, trends, and variability of changes in the active layer and permafrost. The network's two international monitoring components are (1) CALM (Circumpolar Active Layer Monitoring) and the (2) Thermal State of Permafrost (TSP), which is made of an extensive borehole-network covering all permafrost regions. Both programs have been thoroughly overhauled during the International Polar Year 2007-2008 and extended their coverage to provide a true circumpolar network stretching over both Hemispheres. GTN-P has gained considerable visibility in the science community in providing the baseline against which models are globally validated and incorporated in climate assessments. Yet it was until now operated on a voluntary basis, and is now being redesigned to meet the increasing expectations from the science community. To update the network's objectives and deliver the best possible products to the community, the IPA organized a workshop to define the user's needs and requirements for the production, archival, storage and dissemination of the permafrost data products it manages. From the beginning on, GNT-P data was "outfitted" with an open data policy with free data access via the World Wide Web. The existing data, however, is far from being homogeneous: is not yet optimized for databases, there is no framework for data reporting or archival and data documentation is incomplete. As a result, and despite the utmost relevance of permafrost in the Earth's climate system, the data has not been

  15. Application of the Flory-Huggins theory to the solubility of solids in glyceryl trioleate

    USGS Publications Warehouse

    Chiou, Cary T.; Manes, Milton

    1986-01-01

    The conventional thermodynamic deviation for ideal solid–liquid solubilities is modified by substituting the Flory–Huggins model for Raoult's law. A comparison of published data for eleven solides in glyceryl trioleate with the predictions of the conventional and modified equations shows that the significantly higher athermal solubilities from the modified equation are in much better agreement with the experimental data. This suggests that discrepancies between the data and the predictions of the conventional model for ideal systems result from the inappropriate use of Raoult's law for systems with significant solute–solvent size disparity rather than from specific interactions.

  16. A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

    PubMed Central

    Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

    2009-01-01

    Background and purpose: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach: Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Key results: Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. Conclusions and implications: The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes. PMID:19563531

  17. Validation of formability of laminated sheet metal for deep drawing process using GTN damage model

    SciTech Connect

    Lim, Yongbin; Cha, Wan-gi; Kim, Naksoo; Ko, Sangjin

    2013-12-16

    In this study, we studied formability of PET/PVC laminated sheet metal which named VCM (Vinyl Coated Metal). VCM offers various patterns and good-looking metal steel used for appliances such as refrigerator and washing machine. But, this sheet has problems which are crack and peeling of film when the material is formed by deep drawing process. To predict the problems, we used finite element method and GTN (Gurson-Tvergaard-Needleman) damage model to represent damage of material. We divided the VCM into 3 layers (PET film, adhesive and steel added PVC) in finite element analysis model to express the crack and peeling phenomenon. The material properties of each layer are determined by reverse engineering based on tensile test result. Furthermore, we performed the simple rectangular deep drawing and simulated it. The simulation result shows good agreement with drawing experiment result in position, punch stroke of crack occurrence. Also, we studied the fracture mechanism of PET film on VCM by comparing the width direction strain of metal and PET film.

  18. Validation of formability of laminated sheet metal for deep drawing process using GTN damage model

    NASA Astrophysics Data System (ADS)

    Lim, Yongbin; Cha, Wan-gi; Ko, Sangjin; Kim, Naksoo

    2013-12-01

    In this study, we studied formability of PET/PVC laminated sheet metal which named VCM (Vinyl Coated Metal). VCM offers various patterns and good-looking metal steel used for appliances such as refrigerator and washing machine. But, this sheet has problems which are crack and peeling of film when the material is formed by deep drawing process. To predict the problems, we used finite element method and GTN (Gurson-Tvergaard-Needleman) damage model to represent damage of material. We divided the VCM into 3 layers (PET film, adhesive and steel added PVC) in finite element analysis model to express the crack and peeling phenomenon. The material properties of each layer are determined by reverse engineering based on tensile test result. Furthermore, we performed the simple rectangular deep drawing and simulated it. The simulation result shows good agreement with drawing experiment result in position, punch stroke of crack occurrence. Also, we studied the fracture mechanism of PET film on VCM by comparing the width direction strain of metal and PET film.

  19. Parasite impairment by targeting Plasmodium-infected RBCs using glyceryl-dilaurate nanostructured lipid carriers.

    PubMed

    Jain, Soniya A; Basu, Himanish; Prabhu, Priyanka S; Soni, Umangi; Joshi, Medha D; Mathur, Deepak; Patravale, Vandana B; Pathak, Sulabha; Sharma, Shobhona

    2014-08-01

    Antimalarial therapy is a major contributor to declining malaria morbidity and mortality. However, the high toxicity and low bioavailability of current antimalarials and emerging drug resistance necessitates drug-delivery research. We have previously developed glyceryl-dilaurate nanolipid carriers (GDL-NLCs) for antimalarial drug delivery. Here, we show evidence that GDL-NLCs themselves selectively target Plasmodium-infected red blood cells (iRBCs), and cause severe parasite impairment. The glyceryl-dilaurate lipid-moiety was important in the targeting. GDL-NLCs localized to the parasite mitochondrion and uptake led to mitochondrial-membrane polarization and Ca(2+) ion accumulation, ROS release, and stage-specific iRBC lysis. GDL-NLC treatment also resulted in externalization of iRBC-membrane phosphatidylserine and enhanced iRBC clearance by macrophages. GDL-NLC uptake disrupted the parasite-induced tubulovesicular network, which is vital for nutrient import by the parasite. Laser optical trap studies revealed that GDL-NLCs also restored iRBC flexibility. Such restoration of iRBC flexibility may help mitigate the vasculature clogging that can lead to cerebral malaria. We demonstrate the suitability of GDL-NLCs for intravenous delivery of antimalarial combinations artemether-clindamycin and artemether-lumefantrine in the murine model. Complete parasite clearance was achieved at 5-20% of the therapeutic dose of these combinations. Thus, this nanostructured lipid formulation can solubilize lipophilic drugs, selectively target and impair the parasite-infected red cell, and therefore constitutes a potent delivery vehicle for antimalarials.

  20. Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.

    PubMed

    Daidone, Viviana; Cattini, Maria Grazia; Pontara, Elena; Sartorello, Francesca; Gallinaro, Lisa; Marotti, Alberto; Scaroni, Carla; Pagnan, Antonio; Casonato, Alessandra

    2009-02-01

    Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)(n) modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)(n) of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)(n) proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)(21) and (GT)(19) were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15-19) segregated mainly with haplotype 1, long GT repeats (20-24) with haplotype 2 (p < 0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)(n) locus. We conclude that (GT)(n) and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.

  1. A new sunscreen of the cinnamate class: synthesis and enzymatic hydrolysis evaluation of glyceryl esters of p-methoxycinnamic acid.

    PubMed

    de Freitas, Zaida Maria Faria; dos Santos, Elisabete Pereira; da Rocha, João Ferreira; Dellamora-Ortiz, Gisela Maria; Gonçalves, José Carlos Saraiva

    2005-05-01

    Glyceryl esters of p-methoxycinnamic acid, 1,3-dipalmitoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol and 1,3-dioctanoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol were synthesised in an attempt to increase substantivity and decrease eventual undesirable effects of sunscreens of this class. To assess if the glyceryl esters could present a higher stability towards hydrolysis by lipases in the stratum corneum, hydrolysis rates were determined in vitro using a commercial fungal lipase from Rhizomucor miehei. Results presented herein show that the glyceryl esters have similar lambda(max) and epsilon values to sunscreens of the cinnamate class. The ester 1,3-dipalmitoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol presented a 2.8 times lower hydrolysis rate by lipase, in vitro, than the commercial sunscreen 2-ethylhexyl-p-methoxycinnamate (alkyl ester). This finding suggests that this triacylglycerol can possibly have a longer retention time in the skin and consequently promote a more intense and effective antisolar action than the commercial sunscreen.

  2. GTN-G, WGI, RGI, DCW, GLIMS, WGMS, GCOS - What's all this about? (Invited)

    NASA Astrophysics Data System (ADS)

    Paul, F.; Raup, B. H.; Zemp, M.

    2013-12-01

    In a large collaborative effort, the glaciological community has compiled a new and spa-tially complete global dataset of glacier outlines, the so-called Randolph Glacier Inventory or RGI. Despite its regional shortcomings in quality (e.g. in regard to geolocation, gener-alization, and interpretation), this dataset was heavily used for global-scale modelling ap-plications (e.g. determination of total glacier volume and glacier contribution to sea-level rise) in support of the forthcoming 5th Assessment Report (AR5) of Working Group I of the IPCC. The RGI is a merged dataset that is largely based on the GLIMS database and several new datasets provided by the community (both are mostly derived from satellite data), as well as the Digital Chart of the World (DCW) and glacier attribute information (location, size) from the World Glacier Inventory (WGI). There are now two key tasks to be performed, (1) improving the quality of the RGI in all regions where the outlines do not met the quality required for local scale applications, and (2) integrating the RGI in the GLIMS glacier database to improve its spatial completeness. While (1) requires again a huge effort but is already ongoing, (2) is mainly a technical issue that is nearly solved. Apart from this technical dimension, there is also a more political or structural one. While GLIMS is responsible for the remote sensing and glacier inventory part (Tier 5) of the Global Terrestrial Network for Glaciers (GTN-G) within the Global Climate Observing System (GCOS), the World Glacier Monitoring Service (WGMS) is collecting and dis-seminating the field observations. Along with new global products derived from satellite data (e.g. elevation changes and velocity fields) and the community wish to keep a snap-shot dataset such as the RGI available, how to make all these datasets available to the community without duplicating efforts and making best use of the very limited financial resources available must now be discussed. This

  3. Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability.

    PubMed

    Lian, Ruyue; Lu, Yi; Qi, Jianping; Tan, Yanan; Niu, Mengmeng; Guan, Peipei; Hu, Fuqiang; Wu, Wei

    2011-12-01

    Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

  4. Development and evaluation of liquid embolic agents based on liquid crystalline material of glyceryl monooleate.

    PubMed

    Du, Ling-Ran; Lu, Xiao-Jing; Guan, Hai-Tao; Yang, Yong-Jie; Gu, Meng-Jie; Zheng, Zhuo-Zhao; Lv, Tian-Shi; Yan, Zi-Guang; Song, Li; Zou, Ying-Hua; Fu, Nai-Qi; Qi, Xian-Rong; Fan, Tian-Yuan

    2014-08-25

    New type of liquid embolic agents based on a liquid crystalline material of glyceryl monooleate (GMO) was developed and evaluated in this study. Ternary phase diagram of GMO, water and ethanol was constructed and three isotropic liquids (ILs, GMO:ethanol:water=49:21:30, 60:20:20 and 72:18:10 (w/w/w)) were selected as potential liquid embolic agents, which could spontaneously form viscous gel cast when contacting with water or physiological fluid. The ILs exhibited excellent microcatheter deliverability due to low viscosity, and were proved to successfully block the saline flow when performed in a device to simulate embolization in vitro. The ILs also showed good cytocompatibility on L929 mouse fibroblast cell line. The embolization of ILs to rabbit kidneys was performed successfully under monitoring of digital subtraction angiography (DSA), and embolic degree was affected by the initial formulation composition and used volume. At 5th week after embolization, DSA and computed tomography (CT) confirmed the renal arteries embolized with IL did not recanalize in follow-up period, and an obvious atrophy of the embolized kidney was observed. Therefore, the GMO-based liquid embolic agents showed feasible and effective to embolize, and potential use in clinical interventional embolization therapy.

  5. Liquid crystalline phases and their dispersions in aqueous mixtures of glycerol monooleate and glyceryl monooleyl ether.

    PubMed

    Popescu, Georgeta; Barauskas, Justas; Nylander, Tommy; Tiberg, Fredrik

    2007-01-16

    The aqueous phase behavior of mixtures of 1-glycerol monooleate (GMO) and its ether analogue, 1-glyceryl monooleyl ether (GME) has been investigated by a combination of polarized microscopy, X-ray diffraction, and NMR techniques. Three phase diagrams of the ternary GMO/GME/water system have been constructed at 25, 40, and 55 degrees C. The results demonstrate that the increasing amount of GME favors the formation of the reversed phases, evidenced by the transformation of the lamellar and bicontinuous cubic liquid crystalline phases of the binary GMO/water system into reversed micellar or reversed hexagonal phases. For a particular liquid crystalline phase, increasing the GME content has no effect on the structural characteristics and hydration properties, thus suggesting ideal mixing with GMO. Investigations of dispersed nanoparticle samples using shear and a polymeric stabilizer, Pluronic F127, show the possibility of forming two different kinds of bicontinuous cubic phase nanoparticles by simply changing the GMO/GME ratio. Also NMR self-diffusion measurements confirm that the block copolymer, Pluronic F127, used to facilitate dispersion formation, is associated with nanoparticles and provides steric stabilization.

  6. Preparation of multiparticulate vaginal tablet using glyceryl monooleate for sustained progesterone delivery.

    PubMed

    Biradar, Shailesh V; Dhumal, Ravindra S; Shah, Manish H; Paradkar, Anant R; Yamamura, Shigeo

    2009-01-01

    Most of the sustained release vaginal formulations are in the form of bioadhesive gels and tablets. Though proved efficient, their presence in the vagina for a longer time as a bulk produces discomfort and interference with body functioning including sexual activities. Hence, they lack complete patient compliance. In this study, multiparticulate vaginal tablets were prepared by utilizing progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium trisilicate (MTS) and have presented PRO sustained release in simulated vaginal fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting excipients on compression, phase, bioadhesion and drug release properties of prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT) prepared with hydrophilic excipients showed rapid disintegration but, diminished sustaining ability owing to transformation into lamellar phase whereas the multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients presented both rapid disintegration and sustained release in SVF by virtue of cubic phase retention. During bioadhesivity testing, fast disintegration of MHT with formation of uniform and viscous bioadhesive layer on cow mucosa was observed even with a small volume of SVF. As MHT may not produce discomfort and interference, it will be preferred over bioadhesive gel or tablet.

  7. Spray dried glyceryl monooleate-magnesium trisilicate dry powder as cubic phase precursor.

    PubMed

    Shah, Manish H; Biradar, Shailesh V; Paradkar, Anant R

    2006-10-12

    Glyceryl monooleate (GMO) is a polar amphiphilic lipid, which forms different sequential lyotropic liquid crystals upon hydration. GMO has been utilized for various delivery systems and routes of administrations. Owing to sticky and waxy nature of GMO, preparation of oral solid dosage form utilizing GMO is still a challenge for pharmaceutical researchers. Therefore, the objective of the present work was to fabricate dry powder precursors using GMO, which upon hydration in situ forms cubic phase and can be wisely used for fabrication of oral solid dosage forms. In addition to this, dry powder precursor was evaluated for drug loading, in vitro release behavior and in vivo performance of model drug diclofenac sodium (DiNa). The dry powder precursor was obtained by spray-drying GMO with DiNa using magnesium trisilicate (MTS) as adsorbent. The percent drug entrapment of various batches of powder precursor was in the range of 84-93% indicating high content uniformity. SEM and image analysis showed that as the amount of MTS in powder precursor was increased, the particle size decreased. Furthermore, the viscosity of powder precursor was function of amount of MTS. The rate of water uptake of powder precursor was higher due to uniform layer of GMO on the MTS surface, which led to faster transformation of lamellar phase into cubic phase. The polarizing light microscopy confirmed that cubic phase was formed upon hydration of powder precursor. The drug released from powder precursor was initially governed by the cubic phase formed and in later stage it depends upon dynamic swelling behavior of hexagonally packed cylindrical aggregates. The drug loaded powder precursor was found to have more effective and prolonged anti-inflammatory and analgesic activity as compared to pure drug. Thus the dry powder precursor of cubic phase was prepared in which drug release was entirely governed by the mesophases formed.

  8. The Z′ = 12 superstructure of Λ-cobalt(III) sepulchrate trinitrate governed by C—H⋯O hydrogen bonds

    PubMed Central

    Dey, Somnath; Schönleber, Andreas; Mondal, Swastik; Prathapa, Siriyara Jagannatha; van Smaalen, Sander; Larsen, Finn Krebs

    2016-01-01

    Λ-Cobalt(III) sepulchrate trinitrate crystallizes in P6322 with Z = 2 (Z′ = 1/6) at room temperature. Slabs perpendicular to the hexagonal axis comprise molecules Co(sepulchrate) alternating with nitrate groups A and B. Coordinated by six sepulchrate molecules, highly disordered nitrate groups C are accommodated between the slabs. Here we report the fully ordered, low-temperature crystal structure of Co(sep)(NO3)3. It is found to be a high-Z′ structure with Z′ = 12 of the 12-fold superstructure with monoclinic symmetry P21 (c unique). Correlations between structural parameters are effectively removed by refinements within the superspace approach. Superstructure formation is governed by a densification of the packing in conjunction with ordering of nitrate group C, the latter assuming different orientations for each of the Z′ = 12 independent copies in the superstructure. The Co(sep) moiety exhibits small structural variations over its 12 independent copies, while orientations of nitrate groups A and B vary less than the orientations of the nitrate group C do. Molecular packing in the superstructure is found to be determined by short C—H⋯H—C contacts, with H⋯H distances of 2.2–2.3 Å, and by short C—H⋯O contacts, with H⋯O distances down to 2.2 Å. These contacts presumably represent weak C—H⋯O hydrogen bonds, but in any case they prevent further densification of the structure and strengthening of weak N—H⋯O hydrogen bonds with observed H⋯O distances of 2.4–2.6 Å. PMID:27240768

  9. Non-Invasive Vagus Nerve Stimulation as Treatment for Trigeminal Allodynia

    PubMed Central

    Oshinsky, Michael L.; Murphy, Angela L.; Hekierski, Hugh; Cooper, Marnie; Simon, Bruce J.

    2014-01-01

    Implanted vagus nerve stimulation (VNS) has been used to treat seizures and depression. In this study, we explore the mechanism of action of non-invasive vagus nerve stimulation (nVNS) for the treatment of trigeminal allodynia. Rats were repeatedly infused with inflammatory mediators directly onto the dura, which leads to chronic trigeminal allodynia. nVNS for 2min decreases periorbital sensitivity in rats with periorbital trigeminal allodynia for up to 3.5hr after stimulation. Using microdialysis, we quantified levels of extracellular neurotransmitters in the trigeminal nucleus caudalis (TNC). Allodynic rats showed a 7.7±0.9 fold increase in extracellular glutamate in the TNC following i.p. administration of the chemical headache trigger, glyceryl trinitrate (GTN; 0.1mg/kg). Allodynic rats, which received nVNS, had only a 2.3±0.4 fold increase in extracellular glutamate following GTN similar to the response in control naive rats. When nVNS was delayed until 120min after GTN treatment, the high levels of glutamate in the TNC were reversed following nVNS. The nVNS stimulation parameters used in this study did not produce significant changes in blood pressure or heart rate. These data suggest that nVNS may be used to treat trigeminal allodynia. PMID:24530613

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

    PubMed Central

    Izzo, Giuseppe; Di Martino, Natale; Renzi, Adolfo

    2014-01-01

    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. PMID:25089280

  11. Local L-NG-monomethyl-arginine attenuates the vasodilator action of bradykinin in the human forearm.

    PubMed Central

    O'Kane, K P; Webb, D J; Collier, J G; Vallance, P J

    1994-01-01

    1. Studies in animals indicate that bradykinin relaxes blood vessels directly through an action on smooth muscle and indirectly through the release of endothelium-derived mediators. Its precise mechanism of action in the human arterial circulation is not yet known. 2. In this study the effects of a specific inhibitor of nitric oxide synthase, L-NG-monomethyl-arginine (L-NMMA) and noradrenaline on the vasodilator responses to bradykinin were examined in the forearm arterial bed of healthy volunteers. Noradrenaline was used as a control for vasoconstriction by L-NMMA; glyceryl trinitrate (GTN) as a control vasodilator acting independently of the NO synthase enzyme. 3. L-NMMA (4 mumol min-1; 5 min) alone reduced resting forearm blood flow by 44% (P < 0.01; n = 6) confirming that nitric oxide plays an important role in regulating vascular tone. 4. Bradykinin (10 and 100 pmol min-1; 3 min each dose) and GTN (2 and 5 nmol min-1; 3 min each dose) increased forearm blood flow in a dose-dependent manner (percentage changes 171 +/- 17% and 398 +/- 35%, and 176 +/- 21% and 268 +/- 42%, respectively; n = 6). 5. The response to bradykinin, but not that to GTN, was attenuated by L-NMMA compared with noradrenaline (P < 0.05; n = 6), suggesting that bradykinin-induced vasodilatation in the forearm is mediated, at least in part, by stimulating release of nitric oxide. PMID:7833219

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

    PubMed

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

    2015-06-20

    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.

  13. The effect of peroxynitrite decomposition catalyst MnTBAP on aldehyde dehydrogenase-2 nitration by organic nitrates: role in nitrate tolerance.

    PubMed

    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

    2014-11-01

    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

  14. (GT)n Repeat Polymorphism in Heme Oxygenase-1 (HO-1) Correlates with Clinical Outcome after Myeloablative or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Køllgaard, Tania; Kornblit, Brian; Petersen, Jesper; Klausen, Tobias Wirenfeldt; Mortensen, Bo Kok; Brændstrup, Peter; Sengeløv, Henrik; Høgdall, Estrid; Müller, Klaus; Vindeløv, Lars; Andersen, Mads Hald; thor Straten, Per

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)n repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)n repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT. Subsequently, we compared the length of the (GT)n repeat with clinical outcome after HCT. We demonstrated that transplants from a HO-1high donor after MA-conditioning (n = 13) is associated with higher relapse incidence at 3 years (p = 0.01, n = 110). In the NMA-conditioning setting transplantation of HO-1low donor cells into HO-1low recipients correlated significantly with decreased relapse related mortality (RRM) and longer progression free survival (PFS) (p = 0.03 and p = 0.008, respectively). Overall, our findings suggest that HO-1 may play a role for the induction of GVT effect after allogeneic HCT. PMID:27997582

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

    PubMed

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

    1997-07-01

    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.

  16. Temperature data acquired from the DOI/GTN-P Deep Borehole Array on the Arctic Slope of Alaska, 1973-2013

    NASA Astrophysics Data System (ADS)

    Clow, G. D.

    2014-05-01

    A homogeneous set of temperature measurements obtained from the DOI/GTN-P Deep Borehole Array between 1973 and 2013 is presented; DOI/GTN-P is the US Department of the Interior contribution to the Global Terrestrial Network for Permafrost (GTN-P). The 23-element array is located on the Arctic Slope of Alaska, a region of cold continuous permafrost. Most of the monitoring wells are situated on the Arctic coastal plain between the Brooks Range and the Arctic Ocean, while others are in the foothills to the south. The data represent the true temperatures in the wellbores and surrounding rocks at the time of the measurements; they have not been corrected to remove the thermal disturbance caused by drilling the wells. With a few exceptions, the drilling disturbance is estimated to have been on the order of 0.1 K or less by 1989. Thus, most of the temperature measurements acquired during the last 25 yr are little affected by the drilling disturbance. The data contribute to ongoing efforts to monitor changes in the thermal state of permafrost in both hemispheres by the Global Terrestrial Network for Permafrost, one of the primary subnetworks of the Global Terrestrial Observing System (GTOS). The data will also be useful for refining our basic understanding of the physical conditions in permafrost in Arctic Alaska, as well as providing important information for validating predictive models used for climate impact assessments. The processed data are available from the Advanced Cooperative Arctic Data and Information Service (ACADIS) repository at doi:10.5065/D6N014HK.

  17. Using ground data of the Global Terrestrial Network of Permafrost (GTN-P) for the evaluation of ESA Data User Element (DUE) Permafrost remote sensing derived products

    NASA Astrophysics Data System (ADS)

    Elger, K.; Heim, B.; Bartsch, A.; Paulik, Ch.; Duguay, C.; Hachem, S.; Soliman, A.; Boike, J.; Langer, M.; Lantuit, H.

    2012-04-01

    Permafrost is one of the essential climate variables addressed by the Global Terrestrial Observing System (GCOS). Remote sensing data provide area-wide monitoring of e.g. surface temperatures or soil surface status (frozen or thawed state) in the Arctic and Subarctic, where ground data collection is difficult and restricted to local measurements at few monitoring sites. The task of the ESA Data User Element (DUE) Permafrost project is to build-up an Earth observation service for northern high-latitudinal permafrost applications with extensive involvement of the international permafrost research community (www.ipf.tuwien.ac.at/permafrost). The satellite-derived DUE Permafrost products are Land Surface Temperature, Surface Soil Moisture, Surface Frozen and Thawed State, Digital Elevation Model (locally as remote sensing product and circumpolar as non-remote sensing product) and Subsidence, and Land Cover. Land Surface Temperature, Surface Soil Moisture, and Surface Frozen and Thawed State will be provided for the circumpolar permafrost area north of 55° N with 25 km spatial resolution. In addition, regional products with higher spatial resolution were developed for five case study regions in different permafrost zones of the tundra and taiga (Laptev Sea [RU], Central Yakutia [RU], Western Siberia [RU], Alaska N-S transect, [US] Mackenzie River and Valley [CA]). This study shows the evaluation of two DUE Permafrost regional products, Land Surface Temperature and Surface Frozen and Thawed State, using freely available ground truth data from the Global Terrestrial Network of Permafrost (GTN-P) and monitoring data from the Russian-German Samoylov research station in the Lena River Delta (Central Siberia, RU). The GTN-P permafrost monitoring sites with their position in different permafrost zones are highly qualified for the validation of DUE Permafrost remote sensing products. Air and surface temperatures with high-temporal resolution from eleven GTN-P sites in Alaska

  18. Worldwide glacier monitoring as part of policy-related climate observation: development and strategy of the Global Terrestrial Network for Glaciers (GTN-G)

    NASA Astrophysics Data System (ADS)

    Haeberli, W.; Zemp, M.

    2011-12-01

    Internationally coordinated observation of long-term glacier fluctuations as a key indication of global climate changes has a long tradition, starting already in 1894. With the development of the Global Climate Observing System in support of the United Nations Framework Convention on Climate Change, glaciers and ice caps became an Essential Climate Variable within the Global Terrestrial Observing System. A corresponding Global Terrestrial Network for Glaciers (GTN-G) was indeed established as a pilot project to this program. The basic principles followed by GTN-G and similar networks are to be relevant, feasible, comprehensive and understandable to a wider scientific community and the public. Following recommendations by the International Council for Sciences, a contribution should be made to free and unrestricted international sharing of high-quality, long-term and standardized data and information products. A tiered strategy was adopted in order to bridge the gap between detailed process studies at selected field sites with global coverage through satellite remote sensing. Efforts were also made to ensure continuity of long-term measurement series by combining traditional approaches with modern, future-oriented technologies. Today, the GTN-G is jointly run by three operational bodies in glacier monitoring, which are the World Glacier Monitoring Service, the US National Snow and Ice Data Center, and the Global Land Ice Measurements from Space initiative. With an online service, GTN-G provides fast access to regularly updated information on glacier fluctuation and inventory data. Currently, this includes global information from 100,000 glaciers mainly based on aerial photographs and outlines from 95,000 glaciers mainly based on satellite images, length change series from 1,800 glaciers, mass balance series from 250 glaciers, information on special events (e.g., hazards, surges, calving instabilities) from 130 glaciers, as well as 13,000 photographs from some 500

  19. The involvement of the release of nitric oxide in the pharmacological activity of the new furoxan derivative CHF 2363.

    PubMed Central

    Civelli, M.; Giossi, M.; Caruso, P.; Razzetti, R.; Bergamaschi, M.; Bongrani, S.; Gasco, A.

    1996-01-01

    1. The mechanism of action and the pharmacological effects of the new furoxan derivative, CHF 2363 (4-ethoxy-3-phenylsulphonylfuroxan), were investigated. 2. Pre-incubation of CHF 2363 with human platelet-rich plasma produced a concentration-dependent inhibition of the platelet aggregation induced by collagen, adenosine diphosphate (ADP) and platelet activating factor (PAF). The test compound was about 5 times more potent than sodium nitroprusside. 3-Isobutyl-1-methyl-xanthine (IBMX) potentiated the antiaggregating effect of CHF 2363. 3. CHF 2363 was a potent inhibitor of rubbed endothelium rabbit aortic ring contraction induced by noradrenaline. Comparison of IC50 values showed that CHF 2363 was as potent as glyceryl trinitrate (GTN). 4. Increasing concentrations of CHF 2363 elevated platelet guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels. Adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were unaffected. 5. Oxyhaemoglobin reduced all the pharmacological actions of the test compound. Moreover, CHF 2363 concentration-dependently released nitric oxide (NO) in platelet-rich plasma. The NO release was correlated to its ability to increase platelet cyclic GMP levels. 6. After exposure of rat aortic strips to supramaximal concentrations of GTN (550 microM), the vasorelaxant activity of CHF 2363 did not change, although that of GTN decreased about 55 fold. 7. It has been concluded that the new furoxan derivative CHF 2363 exerts a potent antiaggregating and vasorelaxant activity via NO release and increase of cyclic GMP levels. No in vitro cross tolerance between GTN and CHF 2363 was observed. PMID:8799563

  20. ESA DUE Permafrost: Evaluation of remote sensing derived products using ground data from the Global Terrestrial Network of Permafrost (GTN-P)

    NASA Astrophysics Data System (ADS)

    Elger, K. K.; Heim, B.; Lantuit, H.; Boike, J.; Bartsch, A.; Paulik, C.; Duguay, C. R.; Hachem, S.; Soliman, A. S.

    2011-12-01

    The task of the ESA DUE Permafrost project is to build up an Earth observation service for high-latitudinal permafrost applications with extensive involvement of the permafrost research community. The DUE Permafrost products derived from remote sensing are land surface temperature (LST), surface soil moisture (SSM), surface frozen and thawed state (freeze/ thaw), terrain, land cover, and surface waters. Weekly and monthly averages for most of the DUE Permafrost products will be made available for the years 2007-2010. The DUE Permafrost products are provided for the circumpolar permafrost area (north of 55°N) with 25 km spatial resolution. In addition, regional products with higher spatial resolution (300-1000 m/ pixel) were developed for five case study regions. These regions are: (1) the Laptev Sea and Eastern Siberian Sea Region (RU, continuous very cold permafrost/ tundra), (2) the Yakutsk Region (RU, continuous cold permafrost/ taiga), (3) the Western Siberian transect including Yamal Peninsula and Ob Region (RU, continuous to discontinuous/ taiga-tundra), (4) the Alaska Highway Transect (US, continuous to discontinuous/ taiga-tundra), and (5) the Mackenzie Delta and Valley Transect (CA, continuous to discontinuous/ taiga-tundra). The challenge of the programme is to adapt remote sensing products that are well established and tested in agricultural low and mid-latitudinal areas for highly heterogeneous taiga/ tundra permafrost landscapes in arctic regions. Ground data is essential for the evaluation of DUE Permafrost products and is provided by user groups and global networks. A major part of the DUE Permafrost core user group is contributing to GTN-P, the Global Terrestrial Network of Permafrost. Its main programmes, the Circumpolar Active Layer Monitoring (CALM) and the Thermal State of Permafrost (TSP) have been thoroughly overhauled during the last International Polar Year (2007-2008). Their spatial coverage has been extended to provide a true circumpolar

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

    PubMed

    Galeotti, N; Ghelardini, C

    2013-07-15

    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.

  2. Macroangiopathy--does it play a role in young people?

    PubMed

    Donaghue, K C; Robinson, J; McCredie, R; Fung, A; Silink, M; Celermajer, D S

    1998-01-01

    Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5 vs. 9%, (p = 0.0002) and 14 vs. 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The mean urinary albumin excretion rate of the diabetic group with abnormal EDD was 5.76 +/- 2.82 vs. 8.05 +/- 4.88 microg/min in those with normal EDD (p = 0.25). In the diabetic adolescents there was no significant correlation observed between the test for early large vessel disease, HbAlc and tests for diabetic microangiopathy.

  3. Short (GT)n microsatellite repeats in the heme oxygenase-1 gene promoter are associated with antioxidant and anti-inflammatory status in Mexican pediatric patients with sepsis.

    PubMed

    Vázquez-Armenta, Gabriela; González-Leal, Natalia; J Vázquez-de la Torre, Mayra; Muñoz-Valle, José Francisco; Ramos-Márquez, Martha E; Hernández-Cañaveral, Iván; Plascencia-Hernández, Arturo; Siller-López, Fernando

    2013-01-01

    An adequate immune and antioxidant response is a key to the resolution of sepsis. Heme oxygenase-1 (HMOX1) is a stress protein with a polymorphic (GT)n repeat in its gene promoter that regulates its expression in response to oxidative injury, such as that present in sepsis. HMOX1 is the rate-limiting enzyme of heme degradation, and the heme breakdown products, CO, Fe, and bilirubin, are considered to be biologically active metabolites with direct or indirect antioxidant and anti-inflammatory properties. In this study, we investigated the inflammatory and antioxidant response and the relationship with the HMOX1 levels and HMOX1 polymorphism in Mexican septic pediatric patients. In a case-control pilot study, we enrolled 64 septic patients and 72 hospitalized control patients without a diagnosis of sepsis. DNA extracted from buffy coat was genotyped for HMOX1 (GT)n polymorphism by PCR and markers of antioxidant and inflammatory status were quantified in plasma by analysis of the oxygen radical absorbance capacity (ORAC), protein carbonyl (PC), interleukin (IL) 6, IL10, and HMOX1 levels. In septic children, oxidative and inflammatory markers were elevated, and HMOX1 levels were positively correlated with IL10 levels. Genotypic and allelic distribution of HMOX1 polymorphism showed no difference between groups. HMOX1 short-allele septic carriers (< 25 GT repeats) presented favorable ORAC, PC and IL10 levels. This study confirms that an active response against pediatric sepsis involves the expression of HMOX1 and IL10, suggesting that the high antioxidant status associated with HMOX1 short-allele septic carriers might provide a beneficial environment for sepsis resolution.

  4. Exercise training improves conduit vessel function in patients with coronary artery disease.

    PubMed

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

    2003-07-01

    It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.

  5. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells.

    PubMed

    Barsoum, Ivraym B; Smallwood, Chelsea A; Siemens, D Robert; Graham, Charles H

    2014-02-01

    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.

  6. DOI/GTN-P climate and active-layer data acquired in the National Petroleum Reserve: Alaska and the Arctic National Wildlife Refuge, 1998-2011

    USGS Publications Warehouse

    Urban, Frank E.; Clow, Gary D.

    2014-01-01

    This report provides data collected by the climate monitoring array of the U.S. Department of the Interior on Federal lands in Arctic Alaska over the period August 1998 to July 2011; this array is part of the Global Terrestrial Network for Permafrost, (DOI/GTN-P). In addition to presenting data, this report also describes monitoring, data collection, and quality-control methodology. This array of 16 monitoring stations spans lat 68.5°N. to 70.5°N. and long 142.5°W. to 161°W., an area of approximately 150,000 square kilometers. Climate summaries are presented along with quality-controlled data. Data collection is ongoing and includes the following climate- and permafrost-related variables: air temperature, wind speed and direction, ground temperature and soil moisture, snow depth, rainfall, up- and downwelling shortwave radiation, and atmospheric pressure. These data were collected by the U.S. Geological Survey in close collaboration with the Bureau of Land Management and the U.S. Fish and Wildlife Service.

  7. DOI/GTN-P climate and active-layer data acquired in the National Petroleum Reserve-Alaska and the Arctic National Wildlife Refuge

    USGS Publications Warehouse

    Urban, Frank E.; Clow, Gary D.

    2014-01-01

    This report provides data collected by the climate monitoring array of the U.S. Department of the Interior on Federal lands in Arctic Alaska over the period August 1998 to July 2013; this array is part of the Global Terrestrial Network for Permafrost, (DOI/GTN-P). In addition to presenting data, this report also describes monitoring, data collection, and quality-control methods. This array of 16 monitoring stations spans lat 68.5°N. to 70.5°N. and long 142.5°W. to 161°W., an area of approximately 150,000 square kilometers. Climate summaries are presented along with quality-controlled data. Data collection is ongoing and includes the following climate- and permafrost-related variables: air temperature, wind speed and direction, ground temperature, soil moisture, snow depth, rainfall totals, up- and downwelling shortwave radiation, and atmospheric pressure. These data were collected by the U.S. Geological Survey in close collaboration with the Bureau of Land Management and the U.S. Fish and Wildlife Service.

  8. DOI/GTN-P Climate and active-layer data acquired in the National Petroleum Reserve–Alaska and the Arctic National Wildlife Refuge, 1998–2015

    USGS Publications Warehouse

    Urban, Frank E.; Clow, Gary D.

    2017-02-06

    This report provides data collected by the climate monitoring array of the U.S. Department of the Interior on Federal lands in Arctic Alaska over the period August 1998 to July 2015; this array is part of the Global Terrestrial Network for Permafrost (DOI/GTN-P). In addition to presenting data, this report also describes monitoring, data collection, and quality-control methods. The array of 16 monitoring stations spans lat 68.5°N. to 70.5°N. and long 142.5°W. to 161°W., an area of approximately 150,000 square kilometers. Climate summaries are presented along with quality-controlled data. Data collection is ongoing and includes the following climate- and permafrost-related variables: air temperature, wind speed and direction, ground temperature, soil moisture, snow depth, rainfall totals, up- and downwelling shortwave radiation, and atmospheric pressure. These data were collected by the U.S. Geological Survey in close collaboration with the Bureau of Land Management and the U.S. Fish and Wildlife Service.

  9. DOI/GTN-P Climate and active-layer data acquired in the National Petroleum Reserve–Alaska and the Arctic National Wildlife Refuge, 1998–2014

    USGS Publications Warehouse

    Urban, Frank E.; Clow, Gary D.

    2016-03-04

    This report provides data collected by the climate monitoring array of the U.S. Department of the Interior on Federal lands in Arctic Alaska over the period August 1998 to July 2014; this array is part of the Global Terrestrial Network for Permafrost (DOI/GTN-P). In addition to presenting data, this report also describes monitoring, data collection, and quality-control methods. The array of 16 monitoring stations spans lat 68.5°N. to 70.5°N. and long 142.5°W. to 161°W., an area of approximately 150,000 square kilometers. Climate summaries are presented along with quality-controlled data. Data collection is ongoing and includes the following climate- and permafrost-related variables: air temperature, wind speed and direction, ground temperature, soil moisture, snow depth, rainfall totals, up- and downwelling shortwave radiation, and atmospheric pressure. These data were collected by the U.S. Geological Survey in close collaboration with the Bureau of Land Management and the U.S. Fish and Wildlife Service.

  10. Analysis of curing of a sustained release coating formulation by application of NIR spectroscopy to monitor changes associated with glyceryl monostearate.

    PubMed

    Howland, Harris; Fahmy, Raafat; Hoag, Stephen W

    2015-01-01

    For controlled release, latex or pseudolatex coatings to function as designed, it must be cured at temperatures at or slightly above the polymer's glass transition temperature. The focus of this study is to develop an understanding of the curing process and to develop near infrared spectroscopy as a tool for monitoring curing. Differential scanning calorimetry studies were used to determine how the thermal properties of glyceryl monostearate (GMS) and its polymorphic forms relate to the extent of Eudragit® polymer coat curing at different curing temperatures. The different GMS melting endotherms were used to monitor the extent of curing and as references for model development. The calculated melting peak areas for the GMS were plotted versus time and found to be dependent on time and temperature used for curing. Principal component analysis and parallel factor analysis were used to investigate the effect of curing on the films and showed that spectral changes could be could be directly related to the changes associated with the GMS during curing. Partial least square models developed could predict the extent of curing and the final state of GMS post curing.

  11. Glyceryl Tribenzoate: A Flavoring Ingredient, Inhibits the Adoptive Transfer of Experimental Allergic Encephalomyelitis via TGF-β: Implications for Multiple Sclerosis Therapy

    PubMed Central

    Mondal, Susanta; Dasarathi, Sridevi; Pahan, Kalipada

    2017-01-01

    Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Here, we have explored a novel use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS, via TGF-β. Oral feeding of GTB suppressed clinical symptoms of adoptively-transferred relapsing-remitting (RR) EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. GTB also attenuated clinical symptoms of RR-EAE in PLP-TCR transgenic mice and chronic EAE in male C57/BL6 mice. Accordingly, GTB also suppressed perivascular cuffing, preserved the integrity of blood-brain barrier and blood-spinal cord barrier, inhibited inflammation, and stopped demyelination in the CNS of EAE mice. Interestingly, GTB treatment upregulated TGF-β and enriched regulatory T cells (Tregs) in splenocytes as well as in vivo in EAE mice. Blocking TGF-β by neutralizing antibodies abrogated GTB-mediated enrichment of Tregs and protection of EAE. These results suggest that oral GTB may be considered as a possible therapy for MS patients. PMID:28367355

  12. A new class of furoxan derivatives as NO donors: mechanism of action and biological activity.

    PubMed Central

    Ferioli, R; Folco, G C; Ferretti, C; Gasco, A M; Medana, C; Fruttero, R; Civelli, M; Gasco, A

    1995-01-01

    1. The mechanism of action and biological activity of a series of R-substituted and di-R-substituted phenylfuroxans is reported. 2. Maximal potency as vasodilators on rabbit aortic rings, precontracted with noradrenaline (1 microM), was shown by phenyl-cyano isomers and by the 3,4-dicyanofuroxan, characterized by a potency ratio 3-10 fold higher than glyceryl trinitrate (GTN). This effect was reduced upon coincubation with methylene blue or oxyhaemoglobin (10 microM). 3. The furoxan derivatives showing maximal potency as vasodilators were also able to inhibit collagen-induced platelet aggregation, with IC50 values in the sub-micromolar range. 4. The furoxan derivatives were able to stimulate partially purified, rat lung soluble guanylate cyclase; among the most active compounds, the 3-R-substituted isomers displayed a higher level of stimulatory effect than the 4-R analogues. 5. Solutions (0.1 mM) of all the tested furoxans, prepared using 50 mM phosphate buffer, pH 7.4, (diluting 10 mM DMSO stock solutions) did not release nitric oxide (NO) spontaneously; however in presence of 5 mM L-cysteine, a significant NO-releasing capacity was observed, which correlated significantly with their stimulation of the guanylate cyclase activity. PMID:7773542

  13. Inhibitory effects of calcium antagonists on alpha-adrenoceptor-mediated contraction in the human internal mammary artery.

    PubMed Central

    He, G W; Acuff, T E; Ryan, W H; Yang, C Q; Douthit, M B; Bowman, R T; Mack, M J

    1994-01-01

    1. The internal mammary artery has become a preferred coronary bypass graft. Sympathomimetic amines are spasmogens for vasospasm and calcium antagonists are frequently administered drugs perioperatively. The effect of calcium antagonists on alpha-adrenoceptor-mediated contraction depends on the subtype of alpha-adrenoceptor and the type of origin of vascular smooth muscle. This study was designed to investigate the effect of calcium antagonists on alpha-adrenoceptor-mediated contraction in the IMA. 2. Human IMA segments taken from 22 patients undergoing IMA--coronary artery bypass grafting were mounted in an organ bath under the physiological pressure determined from their own length-tension curves. 3. Three ring segments were allocated into three groups. One served as a control and the others were treated with clinically related concentrations of nifedipine (20 or 200 nM) for 25 min before concentration-contraction curves to alpha 1-adrenoceptor agonist methoxamine (MO) or full alpha-adrenoceptor agonist noradrenaline (NA) were established. 4. In separate experiments, the concentration-relaxation curves to nifedipine were established in the IMA rings precontracted with MO (30 microM) or NA (10 microM). Glyceryl trinitrate (GTN, 3 microM) was added to further relax the vessels. 5. Pretreatment with nifedipine (200 nM) only slightly inhibited the MO- (1.74 +/- 0.32 vs 2.88 +/- 0.56 g) or NA- (2.43 +/- 0.66 vs 3.60 +/- 0.82 g) induced contraction without statistical significance (P > 0.05). 6. On the other hand, nifedipine only caused 34.49% relaxation in the MO-precontracted and 24.39% relaxation in the NA-precontracted IMAs. In contrast, GTN caused 76.16% (against MO, P < 0.05) or 92.22% (against NA, P < 0.0001) relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7910471

  14. Glyceryl triacetate for Canavan disease: a low-dose trial in infants and evaluation of a higher dose for toxicity in the tremor rat model.

    PubMed

    Madhavarao, C N; Arun, P; Anikster, Y; Mog, S R; Staretz-Chacham, O; Moffett, J R; Grunberg, N E; Gahl, W A; Namboodiri, A M A

    2009-10-01

    Canavan disease (CD) is a fatal dysmyelinating genetic disorder associated with aspartoacylase deficiency, resulting in decreased brain acetate levels and reduced myelin lipid synthesis in the developing brain. Here we tested tolerability of a potent acetate precursor, glyceryl triacetate (GTA), at low doses in two infants diagnosed with CD, aged 8 and 13 months. Much higher doses of GTA were evaluated for toxicity in the tremor rat model of CD. GTA was given orally to the infants for up to 4.5 and 6 months, starting at 25 mg/kg twice daily, doubling the dose weekly until a maximum of 250 mg/kg reached. Wild-type and tremor rat pups were given GTA orally twice daily, initially at a dose of 4.2 g/kg from postnatal days 7 through 14, and at 5.8 g/kg from day 15 through 23, and thereafter in food (7.5%) and water (5%). At the end of the trial (approximately 90 to 120 days) sera and tissues from rats were analysed for changes in blood chemistry and histopathology. GTA treatment caused no detectable toxicity and the patients showed no deterioration in clinical status. In the high-dose animal studies, no significant differences in the mean blood chemistry values occurred between treated and untreated groups, and no lesions indicating toxicity were detectable in any of the tissues examined. Lack of GTA toxicity in two CD patients in low-dose trials, as well as in high-dose animal studies, suggests that higher, effective dose studies in human CD patients are warranted.

  15. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain.

    PubMed

    Mathew, Raji; Arun, Peethambaran; Madhavarao, Chikkathur N; Moffett, John R; Namboodiri, M A Aryan

    2005-10-01

    Canavan disease (CD) is a fatal genetic neurodegenerative disorder caused by mutations in the gene for aspartoacylase, an enzyme that hydrolyzes N-acetylaspartate (NAA) into L-aspartate and acetate. Because aspartoacylase is localized in oligodendrocytes, and NAA-derived acetate is incorporated into myelin lipids, we hypothesize that an acetate deficiency in oligodendrocytes is responsible for the pathology in CD, and we propose acetate supplementation as a possible therapy. In our preclinical efforts toward this goal, we studied the effectiveness of orally administered glyceryl triacetate (GTA) and calcium acetate for increasing acetate levels in the murine brain. The concentrations of brain acetate and NAA were determined simultaneously after intragastric administration of GTA. We found that the acetate levels in brain were increased in a dose- and time-dependent manner, with a 17-fold increase observed at 1 to 2 h in 20- to 21-day-old mice at a dose of 5.8 g/kg GTA. NAA levels in the brain were not significantly increased under these conditions. Studies using mice at varying stages of development showed that the dose of GTA required to maintain similarly elevated acetate levels in the brain increased with age. Also, GTA was significantly more effective as an acetate source than calcium acetate. Chronic administration of GTA up to 25 days of age did not result in any overt pathology in the mice. Based on these results and the current Food and Drug Administration-approved use of GTA as a food additive, we propose that it is a potential candidate for use in acetate supplementation therapy for CD.

  16. Final amended report on the safety assessment of Ammonium Thioglycolate, Butyl Thioglycolate, Calcium Thioglycolate, Ethanolamine Thioglycolate, Ethyl Thioglycolate, Glyceryl Thioglycolate, Isooctyl Thioglycolate, Isopropyl Thioglycolate, Magnesium Thioglycolate, Methyl Thioglycolate, Potassium Thioglycolate, Sodium Thioglycolate, and Thioglycolic Acid.

    PubMed

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

    2009-01-01

    This safety assessment includes Ammonium and Glyceryl Thioglycolate and Thioglycolic Acid Butyl, Calcium, Ethanolamine, Ethyl, Isooctyl, Isopropyl, Magnesium, Methyl, Potassium, and Sodium Thioglycolate, as used in cosmetics. Thioglycolates penetrate skin and distribute to the kidneys, lungs, small intestine, and spleen; excretion is primarily in urine. Thioglycolates were slightly toxic in rat acute oral toxicity studies. Thioglycolates are minimal to severe ocular irritants. Thioglycolates can be skin irritants in animal and in vitro tests, and can be sensitizers. A no-observable-adverse-effect level for reproductive and developmental toxicity of 100 mg/kg per day was determined using rats. Thioglycolates were not mutagenic, and there was no evidence of carcinogenicity. Thioglycolates were skin irritants in some clinical tests. Clinically significant adverse reactions to these ingredients used in depilatories are not commonly seen, suggesting current products are formulated to be practically nonirritating under conditions of recommended use. Formulators should take steps necessary to assure that current practices are followed.

  17. 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.

    PubMed

    2007-01-01

    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

  18. Influence of nitrovasodilators and endothelin-1 on rheology of human blood in vitro.

    PubMed

    Walter, R; Mark, M; Gaudenz, R; Harris, L G; Reinhart, W H

    1999-10-01

    1. The shear stress of flowing blood profoundly influences the release of endothelium-dependent vasodilative and constrictive factors. Conversely, the influence of these mediators such as nitric oxide (NO) or endothelin-1 (ET-1) on blood rheology remains elusive. In the present study the influence of nitrovasodilators and ET-1 on red blood cell (RBC) shape and whole blood viscosity were investigated. 2. Incubation of whole blood with sodium-nitroprusside (SNP, 10-5 - 10-2 M), glyceryl trinitrate (GTN, 0.0001 - 0.1 mg mL-1), S-nitroso-N-acetylpenicillamine (SNAP, 10-6 - 10-3 M), and the active metabolite of molsidomine (SIN-1, 10-6 - 10-3 M), but not molsidomine (10-6 - 10-3 M), resulted in significantly increased amounts of methaemoglobin, indicating a relevant interaction with RBCs. Treatment with SNP at 10-2 M induced a marked echinocytosis (morphological index: 2.23+/-0.98 vs -0.17+/-0.10; P<0.001) and increased blood viscosity (haematocrit 45%) at a high shear rate of 94.5 s-1 (6.46+/-0.60 vs 5.07+/-0.35 mPa.s; P<0.01) and a low shear rate of 0.1 s-1 (88.6+/-36.8 vs 42.1+/-11.7 mPa.s; P<0.01). Echinocytosis was probably due to cyanide accumulation. SIN-1 at 10-3 M slightly decreased high shear viscosity (4.88+/-0.28 vs 4. 95+/-0.30 mPa.s; P<0.05). SNAP at 10-3 M slightly increased both high (5.14+/-0.23 vs 5.05+/-0.24 mPa.s; P<0.01) and low shear (53.9+/-7.2 vs 51.2+/-5.9 mPa.s; P<0.05) viscosity. Molsidomine and GTN failed to influence whole blood viscosity. ET-1 (10-9 - 10-6 M) had no effect on RBC shape and viscosity. 3. We conclude that the most important modulators of vascular tone, NO and ET-1, do not affect RBC shape and blood viscosity, which is important from both a physiological and a pharmacological point of view.

  19. Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans

    PubMed Central

    Rathod, Krishnaraj S.; Kapil, Vikas; Velmurugan, Shanti; Khambata, Rayomand S.; Siddique, Umme; Khan, Saima; Van Eijl, Sven; Bansal, Jascharanpreet; Pitrola, Kavi; Shaw, Christopher; D’Acquisto, Fulvio; Colas, Romain A.; Marelli-Berg, Federica

    2016-01-01

    BACKGROUND. Cardiovascular disease occurs at lower incidence in premenopausal females compared with age-matched males. This variation may be linked to sex differences in inflammation. We prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males. METHODS. We performed 2 clinical studies in healthy volunteers. In 12 men and 12 women, we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD). In a further 8 volunteers of each sex, we assessed FMD response to glyceryl trinitrate (GTN) at baseline and at 8 hours and 32 hours after typhoid vaccine. In a separate study in 16 men and 16 women, we measured inflammatory exudate mediators and cellular recruitment in cantharidin-induced skin blisters at 24 and 72 hours. RESULTS. Typhoid vaccine induced mild systemic inflammation at 8 hours, reflected by increased white cell count in both sexes. Although neutrophil numbers at baseline and 8 hours were greater in females, the neutrophils were less activated. Systemic inflammation caused a decrease in FMD in males, but an increase in females, at 8 hours. In contrast, GTN response was not altered in either sex after vaccine. At 24 hours, cantharidin formed blisters of similar volume in both sexes; however, at 72 hours, blisters had only resolved in females. Monocyte and leukocyte counts were reduced, and the activation state of all major leukocytes was lower, in blisters of females. This was associated with enhanced levels of the resolving lipids, particularly D-resolvin. CONCLUSIONS. Our findings suggest that female sex protects against systemic inflammation-induced endothelial dysfunction. This effect is likely due to accelerated resolution of inflammation compared with males, specifically via neutrophils, mediated by an elevation of the D-resolvin pathway. TRIAL REGISTRATION. ClinicalTrials.gov NCT01582321 and NRES: City Road and Hampstead Ethics

  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

    PubMed Central

    Malik, Sarthak; Giri, Subhash; Madhu, S. V.; Rathi, Vinita; Banerjee, B. D.; Gupta, Nikhil

    2016-01-01

    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(OH)D levels were studied in all cases and controls. Correlation was also studied between FMD and 25(OH)D. 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(OH)D 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(OH)D 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. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial

    PubMed Central

    2015-01-01

    Summary 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 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), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122. Findings Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7·0 [95% CI −8·5 to −5·6] mm Hg/–3·5 [–4·4 to −2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9·5 [95% CI −11·8 to −7·2] mm Hg/–5·0 [–6·4 to −3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 (95% CI 0·91–1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90–1·22; p=0·55). Interpretation

  2. In vitro suppression of drug-induced methaemoglobin formation by Intralipid(®) in whole human blood: observations relevant to the 'lipid sink theory'.

    PubMed

    Samuels, T L; Willers, J W; Uncles, D R; Monteiro, R; Halloran, C; Dai, H

    2012-01-01

    To provide further evidence for the lipid sink theory, we have developed an in vitro model to assess the effect of Intralipid® 20% on methaemoglobin formation by drugs of varying lipid solubility. Progressively increasing Intralipid concentrations from 4 to 24 mg.ml⁻¹ suppressed methaemoglobin formation by the lipid soluble drug glyceryl trinitrate in a dose-dependent manner (p < 0.001). Both dose and timing of administration of Intralipid to blood previously incubated with glyceryl trinitrate for 10 and 40 min resulted in significant suppression of methaemoglobin formation (p < 0.0001 and p < 0.05, respectively). Mathematical modelling demonstrated that the entire process of methaemoglobin formation by glyceryl trinitrate was slowed down in the presence of Intralipid. Intralipid did not significantly suppress methaemoglobin formation induced by 2-amino-5-hydroxytoluene (partially lipid soluble) or sodium nitrite (lipid insoluble; both p > 0.5). This work may assist determination of the suitability of drugs taken in overdose for which Intralipid might be deployed.

  3. 21 CFR 582.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose Food... substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice....

  4. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... glycerol content: Not to exceed 0.5 percent. Unsaponifiable matter: Not to exceed 0.5 percent. Melting point (Class II): 69 °C-73 °C. (c) The additive is used or intended for use as follows when standards...

  5. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... glycerol content: Not to exceed 0.5 percent. Unsaponifiable matter: Not to exceed 0.5 percent. Melting point (Class II): 69 °C-73 °C. (c) The additive is used or intended for use as follows when standards...

  6. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... glycerol content: Not to exceed 0.5 percent. Unsaponifiable matter: Not to exceed 0.5 percent. Melting point (Class II): 69 °C-73 °C. (c) The additive is used or intended for use as follows when standards...

  7. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... reacting stearic acid with glycerol in the presence of a suitable catalyst. (b) The food additive meets the... number: 186-192. Hydroxyl number: Not to exceed 5.0. Free glycerol content: Not to exceed 0.5...

  8. The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation.

    PubMed

    Noriega, Víctor; Martínez-Laperche, Carolina; Buces, Elena; Pion, Marjorie; Sánchez-Hernández, Noemí; Martín-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; González-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, José B; Martínez, Carmen; Gónzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C; Sampol, Antonia; Jiménez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Díez-Martín, José L; Buño, Ismael

    2015-01-01

    The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.

  9. The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

    PubMed Central

    Buces, Elena; Pion, Marjorie; Sánchez-Hernández, Noemí; Martín-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; González-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, José B.; Martínez, Carmen; Gónzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C.; Sampol, Antonia; Jiménez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Díez-Martín, José L.; Buño, Ismael

    2015-01-01

    The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08–0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients. PMID:26473355

  10. Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation.

    PubMed

    Lewis, Nia C S; Bailey, Damian M; Dumanoir, Gregory R; Messinger, Laura; Lucas, Samuel J E; Cotter, James D; Donnelly, Joseph; McEneny, Jane; Young, Ian S; Stembridge, Mike; Burgess, Keith R; Basnet, Aparna S; Ainslie, Philip N

    2014-03-01

    Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g., chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima-media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2-) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3-4 (acute high altitude) and 12-14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders' FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m s(-1); P = 0.001). These changes persisted at days 12-14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2- increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = -0.53) and chronic (n = 7, r = -0.69; P ≤ 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders

  11. Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

    PubMed Central

    Lewis, Nia C S; Bailey, Damian M; duManoir, Gregory R; Messinger, Laura; Lucas, Samuel J E; Cotter, James D; Donnelly, Joseph; McEneny, Jane; Young, Ian S; Stembridge, Mike; Burgess, Keith R; Basnet, Aparna S; Ainslie, Philip N

    2014-01-01

    Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2–) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m s−1; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2– increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = −0.53) and chronic (n = 7, r = −0.69; P

  12. Acute Dermal Toxicity of Trimethylolethane Trinitrate (TMETN) in Rabbits

    DTIC Science & Technology

    1989-07-01

    and lateral sections of the animals (surface area approximately 300 cm 2 ) were close-clipped with electric clippers (Oster® Model A5, Size 40 blade...13 Nov 84 Cause: Unknown Syndrome : None Gross Comments: All lesions including the liver lesion were considered as incidental findings and not

  13. Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres

    PubMed Central

    Teixeira, Cleber E; Bento, Antonio C; Lopes-Martins, Rodrigo A B; Teixeira, Simone A; von Eickestedt, Vera; Muscará, Marcelo N; Arantes, Eliane C; Giglio, Jose R; Antunes, Edson; de Nucci, Gilberto

    1998-01-01

    The effect of Tityus serrulatus scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade. Tityus serrulatus venom (3–100 μg), acetylcholine (ACh; 0.3–30 nmol) and glyceryl trinitrate (GTN; 0.5–10 nmol) dose-dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3 μM). The selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (ODQ; 30 μM) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30 μM) also inhibited the relaxations induced by Tityus serrulatus venom but, in contrast to ODQ, the inhibition was irreversible. The non-selective NO synthase (NOS) inhibitors NΩ-nitro-L-arginine methyl ester (L-NAME; 10 μM) and NG-iminoethyl-L-ornithine (L-NIO; 30 μM) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh- and Tityus serrulatus venom-induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of L-arginine (300 μM), but not D-arginine (300 μM). The neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM, 100 μM) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), Tityus serrulatus venom and GTN. TRIM was approximately 1,000 times less potent than L-NAME in inhibiting rabbit cerebellar NOS in vitro, as measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. The protease inhibitor aprotinin (Trasylol; 10 μg ml−1) and the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]-BK; 50 nM) did not affect the rabbit isolated corpus cavernosum relaxations induced by Tityus serrulatus venom. The ATP-dependent K+ channel antagonist glibenclamide (10 μM) and the Ca2+-activated

  14. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators.

    PubMed Central

    Salvemini, D; Currie, M G; Mollace, V

    1996-01-01

    We have evaluated the contributions of nitric oxide (NO) and prostacyclin (PGI2) in the in vivo antiplatelet effects of clinically useful nitrovasodilators. In rats, intravenous infusion of three NO donors, glyceryl trinitrate, sodium nitroprusside, or 3'-morpholinosydnonimine, the stable metabolite of molsidomine, released 6-keto PGF1alpha (the stable metabolite of PGI2) and inhibited ex vivo human platelet aggregation to adenosine diphosphate by at least 80%. In in vitro studies, glyceryl trinitrate, sodium nitroprusside, and 3'-morpholinosydnonimine, at clinically attainable concentrations, increased cyclooxygenase activity in endothelial cells (EC), which resulted in a four- to sixfold release of 6-keto PGF1alpha. Pretreatment of the EC with hemoglobin which binds to and inactivates the biological actions of NO, but not by methylene blue (MelB), attenuated the NO-mediated PGI2 from the EC by at least 70%. Release of 6-keto PGF1alpha by the NO donors increased the ability of these compounds to inhibit thrombin-induced human platelet aggregation by at least 10 times; this potentiation was inhibited by hemoglobin but not by MeB. MeB blocked the direct anti-platelet effect of the NO donors in the absence of EC. In summary, we have demonstrated that NO, directly as well as together with an NO-driven cyclooxygenase activation (and hence PGI2), release contributes to the marked anti-platelet effects observed after the in vivo administration of clinically used nitrovasodilators. PMID:8647949

  15. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

    PubMed Central

    Clarkson, P; Adams, M R; Powe, A J; Donald, A E; McCredie, R; Robinson, J; McCarthy, S N; Keech, A; Celermajer, D S; Deanfield, J E

    1996-01-01

    In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process. PMID:8621785

  16. Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness.

    PubMed

    Randsoe, T; Meehan, C F; Broholm, H; Hyldegaard, O

    2015-01-01

    Nitric oxide (NO) releasing agents have, in experimental settings, been shown to decrease intravascular nitrogen bubble formation and to increase the survival rate during decompression sickness (DCS) from diving. The effect has been ascribed to a possible removal of preexisting micronuclei or an increased nitrogen washout on decompression through augmented blood flow rate. The present experiments were conducted to investigate whether a short- or long-acting NO donor [glycerol trinitrate (GTN) or isosorbide-5-mononitrate (ISMN), respectively] would offer the same protection against spinal cord DCS evaluated by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17 s, and spinal cord conduction was studied by measurements of SEPs. Histological samples of the spinal cord were analyzed for lesions of DCS. In total, 58 rats were divided into 6 different treatment groups. The first three received either saline (group 1), 300 mg/kg iv ISMN (group 2), or 10 mg/kg ip GTN (group 3) before compression. The last three received either 300 mg/kg iv ISMN (group 4), 1 mg/kg iv GTN (group 5), or 75 μg/kg iv GTN (group 6) during the dive, before decompression. In all groups, decompression caused considerable intravascular bubble formation. The ISMN groups showed no difference compared with the control group, whereas the GTN groups showed a tendency toward faster SEP disappearance and shorter survival times. In conclusion, neither a short- nor long-acting NO donor had any protective effect against fatal DCS by intravenous bubble formation. This effect is most likely due to a fast ascent rate overriding the protective effects of NO, rather than the total inert tissue gas load.

  17. Biological denitration of propylene glycol dinitrate by Bacillus sp. ATCC 51912.

    PubMed

    Sun, W Q; Meng, M; Kumar, G; Geelhaar, L A; Payne, G F; Speedie, M K; Stacy, J R

    1996-05-01

    In previous studies, bacterial cultures were isolated that had the ability to degrade the nitrate ester glyceryl trinitrate (i.e., nitroglycerin). The goal of the present study was to examine the ability of resting cells and cell-free extracts of the isolate Bacillus sp. ATCC 51912 to degrade the more recalcitrant nitrate ester propylene glycol dinitrate (PGDN). It was observed that the PGDN-denitrating activity was expressed during growth even when cells were cultured in the absence of nitrate esters. This indicates that nitrate esters are not required for expression of denitration activity. Using cell-free extracts, PGDN was observed to be sequentially denitrated to propylene glycol mononitrate (PGMN) and propylene glycol with the second denitration step proceeding more slowly than the first. Also it was observed that dialysis of the cell-free extracts did not affect denitration activity indicating that regenerable cofactors [e.g., NAD(P)H or ATP] are not required for denitration.

  18. Sphincter of Oddi Function and Risk Factors for Dysfunction

    PubMed Central

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

    2017-01-01

    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

  19. Sphincter of Oddi Function and Risk Factors for Dysfunction.

    PubMed

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

    2017-01-01

    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.

  20. An overview of drugs and ancillary equipment for the dentist's emergency kit.

    PubMed

    Chapman, P J

    2003-06-01

    The concept of a basic (i.e., essential) medical emergency kit suitable for a general dental practitioner varies somewhat between different authorities. A practitioner's choice is also dependant on the proximity of medical aid and the nature of the dental practice. Over recent years the trend has been to restrict the items to a minimum, in the interest of both common sense and safety, for example, just oxygen, adrenaline 1:1000, an oral carbohydrate source, glyceryl trinitrate and aspirin as first options. Ancillary equipment should include an oxygen therapy facemask, a pocket mask and a set of oral (Guedel) airways. Two further medication options for consideration are an aerosol bronchodilator and, in certain circumstances, an injectable antihypoglycaemic agent. This paper provides a selective overview of the subject. An absolute necessity is for dentists to be competent in Basic Life Support skills, and to maintain a complete and current medical history for all patients.

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

    PubMed

    Groning, R; Braun, F J

    1996-05-01

    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.

  2. Regulation of Human Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity by Electrophiles in Vitro*

    PubMed Central

    Oelze, Matthias; Knorr, Maike; Schell, Richard; Kamuf, Jens; Pautz, Andrea; Art, Julia; Wenzel, Philip; Münzel, Thomas; Kleinert, Hartmut; Daiber, Andreas

    2011-01-01

    Recently, mitochondrial aldehyde dehydrogenase (ALDH-2) was reported to reduce ischemic damage in an experimental myocardial infarction model. ALDH-2 activity is redox-sensitive. Therefore, we here compared effects of various electrophiles (organic nitrates, reactive fatty acid metabolites, or oxidants) on the activity of ALDH-2 with special emphasis on organic nitrate-induced inactivation of the enzyme, the biochemical correlate of nitrate tolerance. Recombinant human ALDH-2 was overexpressed in Escherichia coli; activity was determined with an HPLC-based assay, and reactive oxygen and nitrogen species formation was determined by chemiluminescence, fluorescence, protein tyrosine nitration, and diaminonaphthalene nitrosation. The organic nitrate glyceryl trinitrate caused a severe concentration-dependent decrease in enzyme activity, whereas incubation with pentaerythritol tetranitrate had only minor effects. 4-Hydroxynonenal, an oxidized prostaglandin J2, and 9- or 10-nitrooleate caused a significant inhibition of ALDH-2 activity, which was improved in the presence of Mg2+ and Ca2+. Hydrogen peroxide and NO generation caused only minor inhibition of ALDH-2 activity, whereas peroxynitrite generation or bolus additions lead to severe impairment of the enzymatic activity, which was prevented by the thioredoxin/thioredoxin reductase (Trx/TrxR) system. In the presence of glyceryl trinitrate and to a lesser extent pentaerythritol tetranitrate, ALDH-2 may be switched to a peroxynitrite synthase. Electrophiles of different nature potently regulate the enzymatic activity of ALDH-2 and thereby may influence the resistance to ischemic damage in response to myocardial infarction. The Trx/TrxR system may play an important role in this process because it not only prevents inhibition of ALDH-2 but is also inhibited by the ALDH-2 substrate 4-hydroxynonenal. PMID:21252222

  3. Synthesis of some novel organic nitrates and comparative in vitro study of their vasodilator profile.

    PubMed

    Chegaev, Konstantin; Lazzarato, Loretta; Marcarino, Paolo; Di Stilo, Antonella; Fruttero, Roberta; Vanthuyne, Nicolas; Roussel, Christian; Gasco, Alberto

    2009-07-09

    Synthesis and structural characterization of the 4-phenylbutane-1,2-diyl dinitrate and of the erythro and threo diastereoisomers of 4-phenylbutane-1,2,3-triyl trinitrate as well as the HPLC chiral separation of the corresponding racemic mixtures are reported. Vasodilator activity of the single enantiomers of these products, of 4-phenylbutyl nitrate, and of the previously described phenylpropyl analogues were assessed on rat aorta strips precontracted with phenylephrine. The compounds were able to relax the contracted tissue in a concentration dependent manner. In the couples of antipodes, a complete lack of enantioselectivity was observed as far as the vasodilator potency is concerned. The concentration response curves of the products, with the exception of those of all the trinitrooxy substituted models, were rightward shifted in the presence of ALDH-2 inhibitors. Mono and dinitrates, but not trinitrates, displayed in vitro cross-tolerance with GTN. This new series of nitric acid esters is an interesting tool that can help to shed light on the unresolved puzzle of nitrate pharmacology. Selected members are worthy of additional study as potential drugs.

  4. Application of a shear-modified GTN model to incremental sheet forming

    NASA Astrophysics Data System (ADS)

    Smith, Jacob; Malhotra, Rajiv; Liu, W. K.; Cao, Jian

    2013-12-01

    This paper investigates the effects of using a shear-modified Gurson-Tvergaard-Needleman model, which is based on the mechanics of voids, for simulating material behavior in the incremental forming process. The problem chosen for analysis is a simplified version of the NUMISHEET 2014 incremental forming benchmark test. The implications of the shear-modification of the model specifically for incremental sheet forming processes are confirmed using finite element analysis. It is shown that including the shear term has a significant effect on fracture timing in incremental forming, which is not well reflected in the observed tensile test simulations for calibration. The numerical implementation and the need for comprehensive calibration of the model are briefly discussed.

  5. Treatment of Xerosis with a Topical Formulation Containing Glyceryl Glucoside, Natural Moisturizing Factors, and Ceramide

    PubMed Central

    Kausch, Martina; Rippke, Frank; Schoelermann, Andrea M.; Filbry, Alexander W.

    2012-01-01

    Objective: To assess the effects of Light Formulation, an oil-in-water emulsion, and Rich Formulation, a water-in-oil emulsion, for the treatment of xerosis. Design: Two double-blind, vehicle-controlled trials (both formulations); a double-blind, randomized regression study (Rich Formulation); and a single-blind tolerability study (Light Formulation). The two formulations were applied twice daily for two weeks, for five days in the regression study, and twice daily for two weeks in the tolerability study. Setting: Studies were conducted during winter in Hamburg, Germany. Participants: A total of 169 subjects were enrolled and 154 completed the studies. The majority were between 50 and 80 years of age, women, all with very dry skin. One withdrew because of an incompatibility reaction that reoccurred with the subject's own body lotion after sun exposure. Measurements: Skin hydration and skin barrier function with both formulations over two weeks, long-term moisturization effect after discontinuation of Rich Formulation, and symptom improvement and skin tolerability with Light Formulation. Results: Vehicle-controlled studies of Light and Rich Formulations demonstrated significantly improved hydration at Weeks 1 and 2 versus the untreated site and vehicles, and significantly reduced transepidermal water loss versus untreated site and basic vehicle. Both products significantly decreased visible dryness and tactile roughness. In the regression study, Rich Formulation maintained significant moisturization six days after treatment discontinuation. Light Formulation reduced symptoms of itching, burning, tightness, tingling, and feeling of dryness. Conclusion: These formulations represent a new approach for the treatment of xerosis by addressing multiple key deficiencies in skin hydration. PMID:22916312

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

    PubMed

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

    2015-10-15

    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.

  7. A safety trial of high dose glyceryl triacetate for Canavan disease.

    PubMed

    Segel, Reeval; Anikster, Yair; Zevin, Shoshana; Steinberg, Avraham; Gahl, William A; Fisher, Drora; Staretz-Chacham, Orna; Zimran, Ari; Altarescu, Gheona

    2011-07-01

    Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis. Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25 g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5 g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8 months and 1 year with high dose GTA, for 4.5 and 6 months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3 months are required in order to test the long-term efficacy of this drug.

  8. Problem Definition Study on the Health Effects of Diethyleneglycol Dinitrate, Triethylenegycol Dinitrate, and Trimethylolethane Trinitrate and Their Respective Combustion Products

    DTIC Science & Technology

    1983-04-01

    propellants without the use of relatively inert diluents such as vaseline, used in some earlier formulations (Phillips, 1943), thereby decreasing...numerous. Information documenting the carcinogenicity, teratogenicity, mutageni- city, eye and skin irritation, skin sensitization, non -oncogenic chronic...sequence of PG > DEG > TEC > TMEG from high to low. At concentrations up to 500 pg per plate, TMEG was not * . bactericidal in five Salmoneila strains

  9. Effect of sublingual nitrate on respiratory reflexes arising from stimulation of juxta-pulmonary capillary (J) receptors by i.v. lobeline and short duration exercise.

    PubMed

    Anand, Ashima; Srivastava, Niraj; Raj, Hans

    2012-05-31

    Juxta-pulmonary capillary (J or pulmonary C fiber) receptors are stimulated by an increase in pulmonary blood flow and give rise to respiratory acceleration and related sensations and inhibit exercise. However, the reverse, i.e., the effect of reducing pulmonary blood flow on their reflexes, is as yet not known. This was investigated by carrying out a placebo-controlled study on the acute effects of a single dose (0.4 mg) of sublingual glyceryl nitrate (GTN), known to shift blood from the central to the peripheral circulation, on the respiratory parameters of exercising healthy subjects and on their responses to i.v. lobeline. In 10 subjects, GTN use delayed the first appearance of respiratory sensations from 9.08 ± 0.9 min to 11 min (P=0.002), reduced the increase in minute ventilation by the end of 10 min of exercise (P=0.003) and increased its duration by 1-4s and doubled it in the remaining one subject. In a majority of 8 of them, the effect of GTN on i.v. lobeline-induced respiratory reflexes and sensations was a significant increase in the dose required (P=0.006) for producing threshold effects and in the latency of their appearance (P=0.003). The latter feature points to a reduction in blood flow in the lung parenchyma where these receptors are located and to which they are sensitive. As this would have led to a reduced stimulation of these receptors, it would account for the delayed appearance of respiratory symptoms, a reduction in ventilatory increase and prolongation of exercise duration. We demonstrated a mechanism of reducing the stimulus level of J receptors by reducing pulmonary blood flow by means of pharmacological sequestration with GTN use, which then led to a reduction in the magnitude of respiratory and viscerosomatic reflexes, while noting at the same time that changes in blood flow in the pulmonary bed do not directly influence limb muscles, tendons and joints which also determine exercise output.

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

    PubMed

    Jin, Yiguang; Yang, Fang; Du, Lina

    2013-12-01

    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.

  11. Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants.

    PubMed

    Madheswaran, Thiagarajan; Baskaran, Rengarajan; Yong, Chul Soon; Yoo, Bong Kyu

    2014-02-01

    The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.

  12. 1-O-alkenyl-sn-glyceryl-3-phosphorylcholine may be a novel posttranslational modification used by the placenta.

    PubMed

    Lowry, Philip

    2011-01-01

    Neurokinin B (NKB) secreted by the placenta was previously found to be raised in preeclampsia and most of the symptoms in this disease appeared to be through progressive activation of the three neurokinin receptors. Further characterization of placental NKB revealed that placental NKB eluted in the approximate position of a 13mer and this was confirmed by TOF mass spectrometry which gave a mass of 1580. Although this is consistent with dimethylated NKB-Gly-Lys-Arg, further characterization (immunological and mass spectrometric fragment analysis) suggested a novel posttranslational modification containing phosphocholine (PC) with some evidence for glycerol and a coordinated alkene. The structure that fits all the data is that a form of platelet activating factor is attached to the aspartyl side chain at position 4 of NKB and thus now implicates placental NKB in the platelet pathology seen in preeclampsia. As it has been reported that it is the PC group per se attached to certain proteins secreted by filarial nematodes imparts them with immune inhibitory properties and thus survival in the host over long periods, attaching PC to placental secretory peptide hormones (also be found on the placental precursors of CRF, ACTH, and activin) may result in a similar situation.

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

    PubMed

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

    2015-03-01

    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.

  14. Collaboration: a solution to the challenge of conducting nursing research in cardiac rehabilitation.

    PubMed

    Gallagher, Robyn; Sadler, Leonie; Kirkness, Ann; Belshaw, Julie; Roach, Kellie; Warrington, Darrell

    2013-01-01

    Clinical nurse leaders such as clinical nurse consultants are required to conduct research and incorporate outcomes of this research into their every day practice. However, undertaking research presents issues for cardiac rehabilitation clinical nurse consultants because they may have competing demands, difficulty with finding replacements and may be relatively isolated from other researchers. The solution to this situation is the formation of a collaborative research team with other cardiac rehabilitation clinical nurse consultants, with the inclusion of an experienced university academic as a mentor for the cardiac rehabilitation clinical nurse consultants working in an Area Health Service encompassing both rural and metropolitan hospitals in New South Wales, Australia. The related research project aimed to evaluate and improve the clients' knowledge and practices related to the use of sublingual glyceryl trinitrate. The team's experiences and suggestions for clinical nurse Leaders are presented in this paper. Essential team characteristics include having shared motivation, good communication practices, flexibility and tolerance, an effective team size, achieving success, willingness to accept challenges and an experienced mentor. The benefits of developing a collaborative team for research led by clinical nurse consultants in cardiac rehabilitation by far outweigh the time and effort involved in the process.

  15. Lateral epicondylalgia: midlife crisis of a tendon.

    PubMed

    Luk, James K H; Tsang, Raymond C C; Leung, H B

    2014-04-01

    The pathogenesis and management of lateral epicondylalgia, or tennis elbow, a common ailment affecting middle-aged subjects of both genders continue to provoke controversy. Currently it is thought to be due to local tendon pathology, pain system changes, and motor system impairment. Its diagnosis is usually clinical, based on a classical history, as well as symptoms and signs. In selected cases, additional imaging (X-rays, ultrasound, and magnetic resonance imaging) can help to confirm the diagnosis. Different treatment modalities have been described, including the use of orthotics, non-steroidal anti-inflammatory drugs, steroid injections, topical glyceryl trinitrate, exercise therapy, manual therapy, ultrasound therapy, laser therapy, extracorporeal shockwave therapy, acupuncture, taping, platelet-rich plasma injections, hyaluronan gel injections, botulinum toxin injections, and surgery. Nevertheless, evidence to select the best treatment is lacking and the choice of therapy depends on the experience of the management team, availability of the equipment and expertise, and patient response. This article provides a snapshot of current medical practice for lateral epicondylalgia management.

  16. Sensitivity analysis of near-infrared functional lymphatic imaging

    PubMed Central

    Weiler, Michael; Kassis, Timothy

    2012-01-01

    Abstract. Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150  μg/mL ICG and 60  g/L albumin. ICG fluorescence can be detected at a concentration of 150  μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time. PMID:22734775

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

    PubMed

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

    2003-12-01

    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.

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

    PubMed

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

    2017-01-01

    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.

  19. Angioplasty of forearm arteries as a finger salvage procedure for patient with end-stage renal failure

    PubMed Central

    Law, Yuk; Chan, Yiu Che; Cheng, Stephen Wing-Keung

    2016-01-01

    Due to the relatively low metabolic demand and extensive collaterals of the upper limb, peripheral arterial disease seldom leads to tissue loss, except in patients with end-stage renal failure (ESRF), rheumatologic diseases, Raynaud’s disease, frostbites, or distal emboli. We report a case of a 51-year-old lady with ESRF who presented to our tertiary referral vascular center with infected gangrene of her right ring finger. Duplex ultrasound showed that her forearm arteries were severely diseased. Digital subtraction angiogram showed severe multilevel stenoses/occlusions in her forearm radial and ulnar arteries. These lesions were successfully angioplastized with 2 mm × 25 mm angioplasty balloon. Completion angiogram showed good radiological results with some post-dilatation spasm which improved with intra-arterial glyceryl trinitrate. The sepsis improved after revascularization, and the distal phalanx was allowed to self-demarcate with dressings and autoamputate with good clinical results. Our case illustrated that even in delayed setting, patients could still benefit from specialist vascular care with a combination of expert care and angioplasty of forearm arteries, with successful salvage of her finger. PMID:27143949

  20. Randomized controlled trial using bosentan to enhance the impact of exercise training in subjects with type 2 diabetes mellitus.

    PubMed

    Schreuder, Tim H A; Duncker, Dirk J; Hopman, Maria T E; Thijssen, Dick H J

    2014-11-01

    In type 2 diabetes patients, endothelin (ET) receptor blockade may enhance blood flow responses to exercise training. The combination of exercise training and ET receptor blockade may represent a more potent stimulus than training alone to improve vascular function, physical fitness and glucose homeostasis. We assessed the effect of an 8 week exercise training programme combined with either ET blockade or placebo on vasculature, fitness and glucose homeostasis in people with type 2 diabetes. In a double-blind randomized controlled trial, brachial endothelium-dependent and ‑independent dilatation (using flow-mediated dilatation and glyceryl trinitrate, respectively), glucose homeostasis (using Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)) and physical fitness (maximal cycling test) were assessed in 18 men with type 2 diabetes (60 ± 6 years old). Subjects underwent an 8 week exercise training programme, with half of the subjects receiving ET receptor blockade (bosentan) and the other half a placebo, followed by reassessment of the tests above. Exercise training improved physical fitness to a similar extent in both groups, but we did not detect changes in vascular function in either group. This study suggests that there is no adaptation in brachial and femoral artery endothelial function after 8 weeks of training in type 2 diabetes patients. Endothelin receptor blockade combined with exercise training does not additionally alter conduit artery endothelial function or physical fitness in type 2 diabetes.

  1. Sensitivity analysis of near-infrared functional lymphatic imaging

    NASA Astrophysics Data System (ADS)

    Weiler, Michael; Kassis, Timothy; Dixon, J. Brandon

    2012-06-01

    Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg/mL ICG and 60 g/L albumin. ICG fluorescence can be detected at a concentration of 150 μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

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

    PubMed

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

    2002-01-01

    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.

  3. Rapid and sensitive measurements of nitrate ester explosives using microchip electrophoresis with electrochemical detection.

    PubMed

    Piccin, Evandro; Dossi, Nicolò; Cagan, Avi; Carrilho, Emanuel; Wang, Joseph

    2009-03-01

    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.

  4. Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate.

    PubMed

    Gori, Tommaso; Daiber, Andreas

    2009-01-01

    Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate). Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced in Western countries. In light of their wide use, and of the (re)introduction of PETN in Western markets, the present review focuses on the novel effects of organic nitrates, describing their potential clinical implications and discussing differences among different compounds. We believe that these recent findings have important clinical implications. Since the side effects of organic nitrates such as nitroglycerin and isosorbides appear to be mediated by reactive oxygen species, care should be taken that drugs with antioxidant properties are co-administered. On the other hand, efforts should be made to clinically exploit the preconditioning effects of these drugs.

  5. [Recent findings on nitrates: their action, bioactivation and development of tolerance].

    PubMed

    Münzel, T

    2008-10-01

    Organic nitrates still are one of the most important drug classes used in the treatment of an acute coronary syndrome and stable coronary artery disease as well as acute and chronic congestive heart failure. The mechanism of vasodilatation comprises the release of nitric oxide, which in turn activates soluble guanylate cyclase and lowers the intracellular calcium content leading to relaxation of vascular smooth muscle. Recent research has demonstrated that highly reactive nitrates, such as nitroglycerin (or glyceryl trinitrate) and pentaerthrityl tetranitrate (PETN) are bioactivated by aldehyde dehydrogenase 2 (ALDH-2), an enzyme located in mitochondria. The enzyme, which bioactivates mono- and dinitrates is not yet identified. Despite being effective in the acute treatment of patients, its long-term efficacy is limited by the development of tolerance to nitrates and of endothelial dysfunction. Both of these side effects of nitrate therapy are due to increased production of reactive oxygen species. This review focuses on new aspects of the process of bioactivation of organic nitrates, the conception of oxidative stress of endothelial dysfunction and of the development of tolerance and their therapeutic consequences. Also discussed are more recent findings on nitric oxide donors such as molsidomine, PETN and the combination treatment of isosorbide dinitrate and hydralazine of patients with coronary artery disease and chronic heart failure.

  6. Patellar Tendinopathy

    PubMed Central

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

    2015-01-01

    Context: 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. Evidence Acquisition: PubMed spanning 1962-2014. Study Design: Clinical review. Level of Evidence: Level 4. Results: 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. Conclusion: 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. PMID:26502416

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

    DTIC Science & Technology

    1981-08-01

    contains water, glycerin , glycol, stearate, beeswax, lanolin oil, sesame oil, glyceryl oleate, glyceryl stearate, isopropyl myristate, myristyl...myristate, stearett-2, triethonolamine, sodium glyceryl oleate phosphate, carbomer-940 fragrance , formaldehyde, FD & CY yellow #5. -23- DIRECTIONAL STIFFNESS

  8. Developing an Excel Decision Support System Using In-Transit Visibility to Decrease DoD Transportation Delays

    DTIC Science & Technology

    2008-03-01

    Visibility (ITV) Architecture ................................................................14 GTN ...39 Table 6. Utilized GTN Data Fields...Transportation Command (USTRANSCOM) Global Transportation Network ( GTN ) gives its customers a seamless, near-real-time capability to access and

  9. Crystal structure of tri-hydrogen bis-{[1,1,1-tris-(2-oxido-ethyl-amino-meth-yl)ethane]-cobalt(III)} trinitrate.

    PubMed

    Sethi, Waqas; Johannesen, Heini V; Morsing, Thorbjørn J; Piligkos, Stergios; Weihe, Høgni

    2015-12-01

    The title compound, [Co2(L)2](3+)·3NO3 (-) [where L = CH3C(CH2NHCH2CH2OH1/2)3], has been synthesized from the ligand 1,1,1-tris-(2-hy-droxy-ethyl-amino-meth-yl)ethane. The cobalt(III) dimer has an inter-esting and uncommon O-H⋯O hydrogen-bonding motif with the three bridging hy-droxy H atoms each being equally disordered over two positions. In the dimeric trication, the octa-hedrally coordinated Co(III) atoms and the capping C atoms lie on a threefold rotation axis. The N atoms of two crystallographically independent nitrate anions also lie on threefold rotation axes. N-H⋯O hydrogen bonding between the complex cations and nitrate anions leads to the formation of a three-dimensional network structure. The compound is a racemic conglomerate of crystals containing either d or l mol-ecules. The crystal used for this study is a d crystal.

  10. The Structure of Glycerol Trinitrate Reductase NerA from Agrobacterium radiobacter Reveals the Molecular Reason for Nitro- and Ene-Reductase Activity in OYE Homologues

    PubMed Central

    Oberdorfer, Gustav; Binter, Alexandra; Wallner, Silvia; Durchschein, Katharina; Hall, Mélanie; Faber, Kurt; Macheroux, Peter; Gruber, Karl

    2013-01-01

    In recent years, Old Yellow Enzymes (OYEs) and their homologues have found broad application in the efficient asymmetric hydrogenation of activated C=C bonds with high selectivities and yields. Members of this class of enzymes have been found in many different organisms and are rather diverse on the sequence level, with pairwise identities as low as 20 %, but they exhibit significant structural similarities with the adoption of a conserved (αβ)8-barrel fold. Some OYEs have been shown not only to reduce C=C double bonds, but also to be capable of reducing nitro groups in both saturated and unsaturated substrates. In order to understand this dual activity we determined and analyzed X-ray crystal structures of NerA from Agrobacterium radiobacter, both in its apo form and in complex with 4-hydroxybenzaldehyde and with 1-nitro-2-phenylpropene. These structures, together with spectroscopic studies of substrate binding to several OYEs, indicate that nitro-containing substrates can bind to OYEs in different binding modes, one of which leads to C=C double bond reduction and the other to nitro group reduction. PMID:23606302

  11. Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster (CHO) Cells With and Without Metabolic Activation. Test Article. Diethylene triamine trinitrate (DETN)

    DTIC Science & Technology

    2010-02-25

    chromatid interchanges between chromosomes leading to four-armed configurations. This could be asymmetrical with formation of a dicentric and an acentric...fragment which may be misaligned and a shortened monocentric chromosome , and where there is no sister chromatid union. Dicentric - an asymmetrical...Test for Chemical Induction of Chromosome Aberrations in Cultured Chinese Hamster Ovary (CHO) Cells With and Without Metabolic Activation Test

  12. In Vivo Test for Chemical Induction of Micronucleated Polychromatic Erythrocytes for Mouse bone Marrow Cells, Test Article, Diethylene Triamine Trinitrate (DETN)

    DTIC Science & Technology

    2010-02-25

    marrow cytogenetics tests : Micronucleus Assay. Revised July 1, 2002, (1). OECD Guideline for Testing of Chemicals, No. 474. Mammalian Erythrocyte... Micronucleus Test . Adopted July 21, 1997, (2). International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals...in the Range Finding Test . Five male and five female mice per dose group per harvest time were used in the Micronucleus Assay. The Range Finding Test

  13. Temperature data acquired from the DOI/GTN-P Deep Borehole Array on the Arctic Slope of Alaska, 1973-2013

    USGS Publications Warehouse

    Clow, Gary D.

    2014-01-01

    System (GTOS). The data will also be useful for refining our basic understanding of the physical conditions in permafrost in Arctic Alaska, as well as providing important information for validating predictive models used for climate impact assessments. The processed data are available from the Advanced Cooperative Arctic Data and Information Service (ACADIS) repository at doi:10.5065/D6N014HK.

  14. Does metformin improve vascular heath in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial

    PubMed Central

    2013-01-01

    Background Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D. Methods/Design This study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8–18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. Discussion This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease. Trial registration Australia New Zealand Clinical Trials Registry ACTRN12611000148976 PMID:23865839

  15. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    PubMed

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies.

  16. Evidence that cranberry juice may improve augmentation index in overweight men.

    PubMed

    Ruel, Guillaume; Lapointe, Annie; Pomerleau, Sonia; Couture, Patrick; Lemieux, Simone; Lamarche, Benoît; Couillard, Charles

    2013-01-01

    The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age ± SD: 45 ± 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease ± SE; -14.0 ± 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

  17. A picosecond laser FAIMS analyzer for detecting ultralow quantities of explosives

    NASA Astrophysics Data System (ADS)

    Chistyakov, Alexander A.; Kotkovskii, Gennadii E.; Sychev, Alexey V.; Odulo, Ivan P.; Bogdanov, Artem S.; Perederiy, Anatoly N.; Spitsyn, Evgeny M.; Shestakov, Alexander V.

    2014-10-01

    A method for detecting ultralow quantities of explosives in air and explosive traces using a state-of-the-art picosecond chip Nd3+:YAG laser has been elaborated. The method combines field asymmetric ion mobility spectrometry (FAIMS) with laser ionization of air samples and laser desorption of analyzed molecules from examined surfaces. Radiation of the fourth harmonic (λ = 266 nm, τpulse = 300 ps, Epulse = 20-150 μJ, ν = 20-300 Hz) was used. The ionization efficiencies for trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), and glyceryl trinitrate (NG) were investigated. The dependences on frequency, pulse energy, peak intensity, and average power for TNT and RDX were determined. It was shown that the optimal peak intensity should be no less than 2•106 W/cm2; at lower peak intensities, the increase of the average laser power in the interval 5-15 mW enhanced the ion signal. The results of detection of TNT, RDX, and NG vapors under these conditions were compared with the results obtained using nanosecond laser excitation. The detected ion signals for all explosives were shown to be two- to threefold higher in the case of picosecond excitation. The FAIMS laser desorption regime was developed where a laser beam exiting the detector after removal of a special plug was used. The results of TNT and RDX detection are presented. The chip Nd3+:YAG laser has a small emitter and a consumed electric power of 25 W. The estimated detection threshold of the prototype picosecond laser FAIMS analyzer of explosives is (1-3)•10-15g/cm3 for TNT vapors.

  18. Erosive Hand Osteoarthritis is Associated with Subclinical Atherosclerosis and Endothelial Dysfunction

    PubMed Central

    Koutroumpas, Athanasios; Giannoukas, Athanasios; Zintzaras, Elias; Exarchou, Ekaterini; Baliakos, Aris; Makaritsis, Konstantinos; Sakkas, Lazaros I.

    2013-01-01

    Chronic inflammatory disorders have been associated with accelerated atherosclerosis and increased cardiovascular (CV) risk. Recent evidence suggests that erosive hand osteoarthritis (EOA) has considerable inflammation; therefore, we examined the presence of subclinical atherosclerosis and endothelial dysfunction in EOA. Twenty-four patients with EOA and 24 age- and sex-matched healthy individuals without clinical OA were included in the study. No subject had a history of CV disease. Intima-media thickness (IMT) and atheromatous plaques in the common carotid and common femoral arteries were measured by Doppler ultrasonography. The endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, sublingual glyceryl trinitrate (NTG)-induced dilatation (NMD) of the brachial artery were assessed. The EOA patients had significantly elevated systolic and diastolic blood pressure (p<0.001 for both). The 10-year risk of general CV disease, as predicted with the Framingham Risk Score, was similar in patients and controls (p=0.18). IMT of both common carotid and common femoral artery were increased in EOA (p=0.01 and p<0.01, respectively), but the frequency of atherosclerotic plaques was not increased. There was no difference in FMD and NMD between the two groups, but the difference between FMD and NMD was increased in EOA. In conclusion, this small controlled study showed an association between EOA and subclinical atherosclerosis that cannot be fully attributed to traditional CV risk factors, as assessed by the Framingham score. These results suggest that chronic, low-grade inflammation is implicated in atherosclerosis in EOA. PMID:24711757

  19. Topical analgesics in the management of acute and chronic pain.

    PubMed

    Argoff, Charles E

    2013-02-01

    Oral analgesics are commonly prescribed for the treatment of acute and chronic pain, but these agents often produce adverse systemic effects, which sometimes are severe. Topical analgesics offer the potential to provide the same analgesic relief provided by oral analgesics but with minimal adverse systemic effects. This article describes the results of a systematic review of the efficacy of topical analgesics in the management of acute and chronic pain conditions. A literature search of MEDLINE/PubMed was conducted using the keywords topical analgesic AND chronic pain OR acute pain OR neuropathic pain and focused only on individual clinical trials published in English-language journals. The search identified 92 articles, of which 65 were eligible for inclusion in the review. The most commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs (n=27), followed by lidocaine (n=9), capsaicin (n=6), amitriptyline (n=5), glyceryl trinitrate (n=3), opioids (n=2), menthol (n=2), pimecrolimus (n=2), and phenytoin (n=2). The most common indications were acute soft tissue injuries (n=18), followed by neuropathic pain (n=17), experimental pain (n=6), osteoarthritis and other chronic joint-related conditions (n=5), skin or leg ulcers (n=5), and chronic knee pain (n=2). Strong evidence was identified for the use of topical diclofenac and topical ibuprofen in the treatment of acute soft tissue injuries or chronic joint-related conditions, such as osteoarthritis. Evidence also supports the use of topical lidocaine in the treatment of postherpetic neuralgia and diabetic neuropathy. Currently, limited evidence is available to support the use of other topical analgesics in acute and chronic pain.

  20. Self-management of coronary heart disease in older patients after elective percutaneous transluminal coronary angioplasty

    PubMed Central

    Dawkes, Susan; Smith, Graeme D; Elliott, Lawrie; Raeside, Robert; Donaldson, Jayne H

    2016-01-01

    Objective To explore how older patients self-manage their coronary heart disease (CHD) after undergoing elective percutaneous transluminal coronary angioplasty (PTCA). Methods This mixed methods study used a sequential, explanatory design and recruited a convenience sample of patients (n = 93) approximately three months after elective PTCA. The study was conducted in two phases. Quantitative data collected in Phase 1 by means of a self-administered survey were subject to univariate and bivariate analysis. Phase 1 findings informed the purposive sampling for Phase 2 where ten participants were selected from the original sample for an in-depth interview. Qualitative data were analysed using thematic analysis. This paper will primarily report the findings from a sub-group of older participants (n = 47) classified as 65 years of age or older. Results 78.7% (n = 37) of participants indicated that they would manage recurring angina symptoms by taking glyceryl trinitrate and 34% (n = 16) thought that resting would help. Regardless of the duration or severity of the symptoms 40.5% (n = 19) would call their general practitioner or an emergency ambulance for assistance during any recurrence of angina symptoms. Older participants weighed less (P = 0.02) and smoked less (P = 0.01) than their younger counterparts in the study. Age did not seem to affect PTCA patients' likelihood of altering dietary factors such as fruit, vegetable and saturated fat consumption (P = 0.237). Conclusions The findings suggest that older people in the study were less likely to know how to correctly manage any recurring angina symptoms than their younger counterparts but they had fewer risk factors for CHD. Age was not a factor that influenced participants' likelihood to alter lifestyle factors. PMID:27594866

  1. Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

    PubMed Central

    Nelson, Tyler S.; Akin, Ryan E.; Weiler, Michael J.; Kassis, Timothy; Kornuta, Jeffrey A.

    2014-01-01

    The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (Peff, pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased Peff of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of Peff and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease. PMID:24430884

  2. Crystal structure of tri­hydrogen bis­{[1,1,1-tris­(2-oxido­ethyl­amino­meth­yl)ethane]­cobalt(III)} trinitrate

    PubMed Central

    Sethi, Waqas; Johannesen, Heini V.; Morsing, Thorbjørn J.; Piligkos, Stergios; Weihe, Høgni

    2015-01-01

    The title compound, [Co2(L)2]3+·3NO3 − [where L = CH3C(CH2NHCH2CH2OH1/2)3], has been synthesized from the ligand 1,1,1-tris­(2-hy­droxy­ethyl­amino­meth­yl)ethane. The cobalt(III) dimer has an inter­esting and uncommon O—H⋯O hydrogen-bonding motif with the three bridging hy­droxy H atoms each being equally disordered over two positions. In the dimeric trication, the octa­hedrally coordinated CoIII atoms and the capping C atoms lie on a threefold rotation axis. The N atoms of two crystallographically independent nitrate anions also lie on threefold rotation axes. N—H⋯O hydrogen bonding between the complex cations and nitrate anions leads to the formation of a three-dimensional network structure. The compound is a racemic conglomerate of crystals containing either d or l mol­ecules. The crystal used for this study is a d crystal. PMID:26870462

  3. Evaluation of a Test Article in the Salmonella typhimurium/Ecscherichia coli Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat Liver S-9. Test Article - Diethylene triamine trinitrate (DETN)

    DTIC Science & Technology

    2010-02-25

    the culture is required in order to be metabolized prior to plating . The Pre-Incubation method of treatment is perfonned at the request ofthe...Kalamazoo, Michigan. CULTURE CONDITIONS The cells were grown in Oxoid Nutrient Broth No.2 (Oxoid LTD, Hampshire, England) in a shaker incubator... aseptically placed in the center of the agar overlay. Ten ilL of a 1.0 mg/mL crystal violet solution was then added to the disc. The plates were

  4. Joint Deployment and Redeployment Operations

    DTIC Science & Technology

    2007-11-02

    GCCS, GCSS, and GTN development efforts. To provide full functionality, these planning and execution systems must have a modeling and simulation...development and integration of the global transportation network ( GTN ) into the Global Command and Control System (GCCS) and the Global Combat Support...ongoing movements in the DTS through GTN . GTN provides the central data base for all scheduled transportation movements. The central data base for all

  5. Role of plasma S-nitrosothiols in regulation of blood pressure in anesthetized rabbits with special references to hypotensive effects of acetylcholine and nitrovasodilators.

    PubMed

    Ishibashi, Takaharu; Miwa, Tomoko; Nishizawa, Naoki; Shinkawa, Ikumi; Yoshida, Junko; Kawada, Tomie; Nishio, Matomo

    2011-01-01

    The regulatory role of plasma nitrosothiols (R-SNOs) under steady-state conditions and their possible contribution to pharmacological vasodilation were systematically examined in anesthetized rabbits. Nitrosocystein (Cys-NO), S-nitrosoglutathione (G-SNO), and S-nitrosoalbumin (Alb-SNO) were determined by HPLC-Saville's method with respective sensitivities of 1, 1, and 5 nM. These R-SNOs were not detected under steady-state conditions even in the presence of N-ethylmaleimide, a thiol protective agent used to prevent transnitrosation of R-SNOs. Development of plasma Alb-SNO below 300 nM was observed after intravenous injection (i.v.) of nitric oxide (NO) solution (0.1 to 3 ml/g), NOC7 (an NO releasing agent, above 1 µg/kg), and a low dose of Alb-SNO (10 nmol/kg). However, blood pressure was not significantly reduced by NO solution or Alb-SNO. Intravenous injection of a high dose of Alb-SNO (300 nmol/kg) significantly reduced blood pressure with the appearance not only Alb-SNO in micromolar level in plasma, but also G-SNO in lesser degree. Conversely, the hypotensive effect of Cys-NO (300 nmol/kg, i.v.) and G-SNO (300 nmol/kg, i.v.) accompanied development of Alb-SNO (micromolar level), but not Cys-NO or G-SNO in plasma. R-SNOs were not found in plasma during profound hypotension induced by acetylcholine (10 and 30 µg/kg/min, continuous i.v.), glyceryl trinitrate (100 µg/kg, i.v.), sodium nitroprusside (100 µg/kg, i.v.), and isosorbide dinitrate (300 µg/kg, i.v.). These results indicate that R-SNOs do not play an important role under unstimulated condition. In addition, plasma R-SNOs may not be involved in pharmacological vasodilation where contributions of NO or R-SNOs are suggested.

  6. [Arterial rigidity and endothelial dysfunction in obese children].

    PubMed

    Aggoun, Y; Tounian, P; Dabbas-Tyan, M; Massih, T Abdel; Girardet, J P; Ricour, C; Sidi, D; Bonnet, D

    2002-01-01

    Obesity is a cardiovascular risk factor in adults. Poorly is known about effect of obesity on cardiovascular system in children. Mechanical properties of a great elastic trunk, the common carotid artery (CCA) and endothelium function of the brachial artery were studied in 130 obese children (age: 12 +/- 3 years, body mass index (BMI): 29 +/- 5.5 kg/m2, without hypertension (115 +/- 19/58 +/- 8 mmHg). These patients had a vascular high resolution echographical analysis. Cross sectional compliance (CSC), cross sectional distensibility (CSD) and incremental elastic modulus (Einc) were analysed at the CCA site. The brachial artery dilation was measured after hyperthemia (flow mediated dilation, FMD), an endothelium dependent function and after sublingually glyceryl trinitrate (GTNMD), an independent endothelium function. Fat mass composition and distribution were assessed by dual-energy X-ray absorptiometry in 70 patients. In 50 obese patients an oral glucose tolerance test was done to determine insulin resistance. The obese children had significantly lower CSC and CSD than the healthy controls (respectively 0.12 +/- 0.04 vs 0.14 +/- 0.05 mm2.mmHg-1; p < 0.05 and 0.5 +/- 0.2 vs 0.8 +/- 0.4 mmHg(-1).10(-2); p < 0.001). Obese children had higher value than the controls for Einc (2.4 +/- 0.4 vs 1 +/- 0.24 mmHg.10(3); p < 0.001) that correlated poorly with fasting insulin concentrations (r = 0.34; p < 0.06) and BMI (r = 0.34; p < 0.01). FMD was significantly lower in obese children than in controls (6 +/- 3 vs 8 +/- 4%, p < 0.01) without modification of GTNMD (17 +/- 6 vs 18 +/- 7%, NS). These two parameters were respectively correlated with the android fat distribution (r = 0.36; p < 0.01; r = 0.49; p < 0.001). The CCA stiffness of obese children is linked to the amount of the overweight and to insulin resistance. The android fat distribution is related to endothelium dysfunction.

  7. 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.

    PubMed

    2007-01-01

    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.

  8. Dietary supplement with vitamin C prevents nitrate tolerance.

    PubMed Central

    Bassenge, E; Fink, N; Skatchkov, M; Fink, B

    1998-01-01

    Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We tested the effects of vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h) in nine healthy subjects. Tolerance development was monitored by changes in arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three different series in the same subjects. GTN treatment caused an immediate rise in arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating GTN, the a/b ratio progressively decreased and reached basal levels. In addition, there was a progressive loss of the orthostatic decrease in blood pressure. However, coadministration of Vit-C and GTN fully maintained the GTN-induced changes in the orthostatic blood pressure, and the rise of a/b ratio was augmented by 310% for the duration of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated platelets, which was also reversed by Vit-C administration. These findings demonstrate that dietary supplementation with Vit-C eliminates vascular tolerance and concomitant upregulation of ex vivo-washed platelet activity during long-term nonintermittent administration of GTN in humans. PMID:9649558

  9. The Effects of Platelet-Activating Factor (PAF) and a PAF Antagonist (CV-3988) on Smoke Inhalation Injury in an Ovine Model,

    DTIC Science & Technology

    1992-03-01

    decyl-2-acetyl-sn-glyceryl-3- phosphorylcholine ) has following PAF injection. In models of endotoxin shock, been reported to be one of the principal...instillation of 1-0-octadecyl-2- 25. Traber DL, Herndon DN, Stein MD, et al: The pulmonary lesion acetyl-sn-glyceryl-3- phosphorylcholine or of native platelet-ac...glyceryl ether phosphorylcholine infusion in the change (abstr). Proceedings of the American Burn Association rabbit. Am Rev Respir Dis 124:416, 1981 22nd

  10. An Analysis of Time Series Forecasting Methods for the Airlift of Palletized Sustainment Cargo

    DTIC Science & Technology

    2010-06-01

    is difficult to extend their models to the post-channel system, the nature of the research alone highlights the complex nature of predicting airlift...eliminated, bridge applications have attempted to band-aid the gaps. One such system is USTRANSCOM’s Global Transportation Network ( GTN ). GTN bridges the...d.). IDE and GTN form the basis of a recent partnership between DLA and USTRANSCOM in an effort to improve the end-to-end supply visibility

  11. MNE5 Coalition Logistics Information Sharing (NATO IR Decomposition Methodology)

    DTIC Science & Technology

    2008-07-16

    Populate IR: The name of the Authoritative Data Source Example: Global Transportation Network ( GTN ) • Link to Source / Systems: The connecting link...best chance possible to locate it. Additionally, if there is a document that could be modified to support exchanging this information list it and...COMMERCI AL BILL OF LADING FROM WHICH THE FREIGHT- LADING- BILL WAS Nation al, CTF GTN GTN.doc 18 UNCLASSIFIED –APPROVED FOR PUBLIC RELEASE

  12. MNE 5 Coalition Logistics Information Sharing (NATO IR Decomposition Methodology)

    DTIC Science & Technology

    2008-07-16

    Populate IR: The name of the Authoritative Data Source Example: Global Transportation Network ( GTN ) • Link to Source / Systems: The connecting...the best chance possible to locate it. Additionally, if there is a document that could be modified to support exchanging this information list it...THE COMMERCI AL BILL OF LADING FROM WHICH THE FREIGHT- LADING- BILL WAS Nation al, CTF GTN GTN.doc 18 UNCLASSIFIED –APPROVED FOR PUBLIC

  13. Joint Tactics, Techniques, and Procedures for Foreign Humanitarian Assistance

    DTIC Science & Technology

    2007-11-02

    Transition Model ..................................................................................... IV-23 V-1 Types of Training...DALIS for its basic design. II-14 Chapter II JP 3-07.6 • Global Transportation Network ( GTN ). GTN is a standardized DOD system that provides access to...transportation data inputs from a wide variety of in-transit visibility systems. Users can query the GTN database to track cargo and passengers from

  14. Nitroglycerin Tolerance in Caveolin-1 Deficient Mice

    PubMed Central

    Mao, Mao; Varadarajan, Sudhahar; Fukai, Tohru; Bakhshi, Farnaz R.; Chernaya, Olga; Dudley, Samuel C.; Minshall, Richard D.; Bonini, Marcelo G.

    2014-01-01

    Nitrate tolerance developed after persistent nitroglycerin (GTN) exposure limits its clinical utility. Previously, we have shown that the vasodilatory action of GTN is dependent on endothelial nitric oxide synthase (eNOS/NOS3) activity. Caveolin-1 (Cav-1) is known to interact with NOS3 on the cytoplasmic side of cholesterol-enriched plasma membrane microdomains (caveolae) and to inhibit NOS3 activity. Loss of Cav-1 expression results in NOS3 hyperactivation and uncoupling, converting NOS3 into a source of superoxide radicals, peroxynitrite, and oxidative stress. Therefore, we hypothesized that nitrate tolerance induced by persistent GTN treatment results from NOS3 dysfunction and vascular toxicity. Exposure to GTN for 48–72 h resulted in nitrosation and depletion (>50%) of Cav-1, NOS3 uncoupling as measured by an increase in peroxynitrite production (>100%), and endothelial toxicity in cultured cells. In the Cav-1 deficient mice, NOS3 dysfunction was accompanied by GTN tolerance (>50% dilation inhibition at low GTN concentrations). In conclusion, GTN tolerance results from Cav-1 modification and depletion by GTN that causes persistent NOS3 activation and uncoupling, preventing it from participating in GTN-medicated vasodilation. PMID:25158065

  15. Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin*

    PubMed Central

    Opelt, Marissa; Eroglu, Emrah; Waldeck-Weiermair, Markus; Russwurm, Michael; Koesling, Doris; Malli, Roland; Graier, Wolfgang F.; Fassett, John T.; Schrammel, Astrid; Mayer, Bernd

    2016-01-01

    Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (≤1 μm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (≤1 μm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN-induced activation of sGC. The addition of 1 μm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN-derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild-type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC. PMID:27679490

  16. 40 CFR 180.920 - Inert ingredients used pre-harvest; exemptions from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .../stabilizer Boric acid Sequestrant Buffalo gourd root powder (Cucurbita foetidissima root powder); or.... 31075-24-8) For use in pesticide formulations applied to cotton or wheat only Adjuvant or water... water-soluble film Glyceryl triacetate Stabilizer Glyceryl tris-12-hydroxystearate Flow control...

  17. 21 CFR 172.832 - Monoglyceride citrate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN... glyceryl monooleate and its citric acid monoester manufactured by the reaction of glyceryl monooleate with... addition to oils and fats whereby the additive does not exceed 200 parts per million of the combined...

  18. The anti-inflammatory and analgesic action of transdermal glyceryltrinitrate in the treatment of infusion-related thrombophlebitis.

    PubMed Central

    Berrazueta, J. R.; Poveda, J. J.; Ochoteco, J.; Amado, J. A.; Puebla, F.; Salas, E.; Sarabia, M.

    1993-01-01

    We have carried out a prospective double-blind randomized study in 40 patients with infusion-related thrombophlebitis. Twenty-two patients were included in the glyceryltrinitrate (GTN) ointment group and 18 patients in the control heparinoid group. Pain was assessed by an analogue scale. At 48 hours the analgesic index was 84.6 +/- 18 units with GTN and 49 +/- 45 units with heparinoid ointment (P < 0.01). Faster relief of oedema was also observed in the GTN-treated group. All signs of thrombophlebitis were relieved in less than 4 days in the GTN group compared with 9 days in the controls (P < 0.005). We conclude that transdermal GTN is useful therapy for infusion-related thrombophlebitis showing evidence of anti-inflammatory and analgesic effect. PMID:8383319

  19. Involvement of phorbol-12-myristate-13-acetate-induced protein 1 in goniothalamin-induced TP53-dependent and -independent apoptosis in hepatocellular carcinoma-derived cells

    SciTech Connect

    Kuo, Kung-Kai; Chen, Yi-Ling; Chen, Lih-Ren; Li, Chien-Feng; Lan, Yu-Hsuan; Chang, Fang-Rong; Wu, Yang-Chang; Shiue, Yow-Ling

    2011-10-01

    The objective was to investigate the upstream apoptotic mechanisms that were triggered by a styrylpyrone derivative, goniothalamin (GTN), in tumor protein p53 (TP53)-positive and -negative hepatocellular carcinoma (HCC)-derived cells. Effects of GTN were evaluated by the flow cytometry, alkaline comet assay, immunocytochemistry, small-hairpin RNA interference, mitochondria/cytosol fractionation, quantitative reverse transcription-polymerase chain reaction, immunoblotting analysis and caspase 3 activity assays in two HCC-derived cell lines. Results indicated that GTN triggered phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, also known as NOXA)-mediated apoptosis via TP53-dependent and -independent pathways. In TP53-positive SK-Hep1 cells, GTN furthermore induced TP53 transcription-dependent and -independent apoptosis. After GTN treatment, accumulation of reactive oxygen species, formation of DNA double-strand breaks, transactivation of TP53 and/or PMAIP1 gene, translocation of TP53 and/or PMAIP1 proteins to mitochondria, release of cytochrome c from mitochondria, cleavage of caspases and induction of apoptosis in both cell lines were sustained. GTN might represent a novel class of anticancer drug that induces apoptosis in HCC-derived cells through PMAIP1 transactivation regardless of the status of TP53 gene. - Highlights: > Goniothalamin (GTN) induced apoptosis in hepatocellular carcinomas-derived cells. > The apoptosis induced by GTN is PMAIP1-dependent, regardless of TP53 status. > The apoptosis induced by GTN might be TP53 transcription-dependent or -independent. > GTN-induced apoptosis is mitochondria- and caspases-mediated.

  20. Solid lipid extrusion of sustained release dosage forms.

    PubMed

    Reitz, Claudia; Kleinebudde, Peter

    2007-09-01

    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.

  1. 5-Acetyl goniothalamin suppresses proliferation of breast cancer cells via Wnt/β-catenin signaling.

    PubMed

    Boonmuen, Nittaya; Thongon, Natthakan; Chairoungdua, Arthit; Suksen, Kanoknetr; Pompimon, Wilart; Tuchinda, Patoomratana; Reutrakul, Vichai; Piyachaturawat, Pawinee

    2016-11-15

    Styryl lactones are plant-derived compounds from genus Goniothalamus with promising anti-proliferation and anticancer properties. However, the exact mechanism and the target for their activities remained unclear. In the present study, we investigated the effect of 5-acetyl goniothalamin (5GTN) from Goniothalamus marcanii on Wnt/β-catenin signaling pathway which is a key regulator in controlling cell proliferation in breast cancer cells (MCF-7 and MDA-MB-231). 5GTN, a naturally occurring derivative of goniothalamin (GTN) mediated the toxicity to MCF-7 and MDA-MB-231 cells in a dose- and time- related manner, and was more potent than that of GTN. 5GTN strongly inhibited cell proliferation and markedly suppressed transcriptional activity induced by β-catenin in luciferase reporter gene assay. In consistent with this view, the expression of Wnt/β-catenin signaling target genes including c-Myc, cyclin D1 and Axin2 in MCF-7 and MDA-MB-231 cells were suppressed after treatment with 5GTN. It was concomitant with cell cycle arrest at G1 phase and cell apoptosis in MCF-7 cells. In addition, 5GTN enhanced glycogen synthase kinase (GSK-3β) activity and therefore reduced the expression of active form of β-catenin protein in MCF-7 and MDA-MB-231 cells. Taken together, 5GTN exhibited a promising anticancer effect against breast cancer cells through an inhibition of Wnt/β-catenin signaling. This pathway may be served as a potential chemotherapeutic target for breast cancer by 5GTN.

  2. Enabling the Interoperability of Large-Scale Legacy Systems

    DTIC Science & Technology

    2008-01-01

    with two schemas to evaluate IMT on the mapping task: (1) the WPS- GTN schema and (2) the Master Model schema (see Table 1). This task...focuses on mapping WPS- GTN to the Master Model , which has 12,383 fields. This pair of schemas has 10,302,656 1:1 possible field mappings. USTRANSCOM...provided 597 of the 832 mappings from WPS- GTN to the Master Model , which we used as the Gold Standard for our investigation. There were no mappings

  3. Lipstick dermatitis due to C18 aliphatic compounds.

    PubMed

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

    1987-04-01

    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.

  4. 76 FR 5796 - Gas Transmission Northwest Corporation; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... Energy Regulatory Commission Gas Transmission Northwest Corporation; Notice of Application January 26, 2011. Take notice that on January 14, 2011, Gas Transmission Northwest Corporation (GTN), 717 Texas..., Manager, Project Determinations & Regulatory Administration, Gas Transmission Northwest Corporation,...

  5. The Rise of Air Mobility and Its Generals

    DTIC Science & Technology

    2008-03-01

    sorties two to one.3 “Never before in the history of warfare have so many air missions during wartime been air mobility over such an extended period.”4...Transportation Network. “ GTN gives its customers located any- where in the world a seamless, near-real-time capability to access—and em- ploy...transportation and deployment information. GTN is an automated command and control information system that supports the family of trans- portation users and

  6. Rate-Dependent Homogenization Based Continuum Plasticity Damage Model for Dendritic Cast Aluminum Alloys

    DTIC Science & Technology

    2011-01-01

    The overall framework of this rate-dependent HCPD model follows the structure of the anisotropic Gursen- Tvergaard-Needleman( GTN ) type elasto...with evolving porosity. The HCPD model follows the Gurson-Tvergaard-Needleman or GTN models framework established in [14, 15, 16, 17] that account for...this method. In [32, 33] the VCFEM model has been extended for rate-dependent elastic- viscoplastic porous ductile material. Micromechanical analysis

  7. Expeditionary Border Security Operations: Eliminating the Seams

    DTIC Science & Technology

    2008-05-22

    CTC model as they actively and passively support TCO and GTN activity. Al Qaeda has operated training camps in the Sudan in the past and conducted...threat model and demonstrate the danger to US national security interests. The rise of TCOs and GTNs as a result of the rapid globalization of the...Initiative TCO- Transnational Criminal Organization GTN - Global Terrorist Network GSPC- Groupe Salafiste pour la Predication et le Combat AQIM

  8. Circulating Cell Free DNA in the Diagnosis of Trophoblastic Tumors

    PubMed Central

    Openshaw, Mark R.; Harvey, Richard A.; Sebire, Neil J.; Kaur, Baljeet; Sarwar, Naveed; Seckl, Michael J.; Fisher, Rosemary A.

    2015-01-01

    Gestational trophoblastic neoplasia (GTN) represents a group of diseases characterized by production of human chorionic gonadotropin (hCG). Since non-gestational tumors may occasionally secrete hCG, histopathological diagnosis is important for appropriate clinical management. However, a histopathological diagnosis is not always available. We therefore investigated the feasibility of extracting cell free DNA (cfDNA) from the plasma of women with GTN for use as a “liquid biopsy” in patients without histopathological diagnosis. cfDNA was prepared from the plasma of 20 women with a diagnosis of GTN and five with hCG-secreting tumors of unknown origin. Genotyping of cfDNA from the patient, genomic DNA from her and her partner and DNA from the tumor tissue identified circulating tumor DNA (ctDNA) (from 9% to 53% of total cfDNA) in 12 of 20 patients with GTN. In one case without a tissue diagnosis, ctDNA enabled a diagnosis of GTN originating in a non-molar conception and in another a diagnosis of non-gestational tumor, based on the high degree of allelic instability and loss of heterozygosity in the ctDNA. In summary ctDNA can be detected in the plasma of women with GTN and can facilitate the diagnosis of both gestational and non-gestational trophoblastic tumors in cases without histopathological diagnosis. PMID:26981554

  9. Circulating Cell Free DNA in the Diagnosis of Trophoblastic Tumors.

    PubMed

    Openshaw, Mark R; Harvey, Richard A; Sebire, Neil J; Kaur, Baljeet; Sarwar, Naveed; Seckl, Michael J; Fisher, Rosemary A

    2016-02-01

    Gestational trophoblastic neoplasia (GTN) represents a group of diseases characterized by production of human chorionic gonadotropin (hCG). Since non-gestational tumors may occasionally secrete hCG, histopathological diagnosis is important for appropriate clinical management. However, a histopathological diagnosis is not always available. We therefore investigated the feasibility of extracting cell free DNA (cfDNA) from the plasma of women with GTN for use as a "liquid biopsy" in patients without histopathological diagnosis. cfDNA was prepared from the plasma of 20 women with a diagnosis of GTN and five with hCG-secreting tumors of unknown origin. Genotyping of cfDNA from the patient, genomic DNA from her and her partner and DNA from the tumor tissue identified circulating tumor DNA (ctDNA) (from 9% to 53% of total cfDNA) in 12 of 20 patients with GTN. In one case without a tissue diagnosis, ctDNA enabled a diagnosis of GTN originating in a non-molar conception and in another a diagnosis of non-gestational tumor, based on the high degree of allelic instability and loss of heterozygosity in the ctDNA. In summary ctDNA can be detected in the plasma of women with GTN and can facilitate the diagnosis of both gestational and non-gestational trophoblastic tumors in cases without histopathological diagnosis.

  10. Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation.

    PubMed

    Orlikova, Barbora; Schumacher, Marc; Juncker, Tom; Yan, Choo Chee; Inayat-Hussain, Salmaan H; Hajjouli, Shéhérazade; Cerella, Claudia; Dicato, Mario; Diederich, Marc

    2013-09-01

    (R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 μM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 μM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.

  11. Propellant Combustion and Propulsion: Nine Year Index and Abstracts of Publications by Princeton University 1968 - 1976.

    DTIC Science & Technology

    1976-12-01

    plastisol NC with TMETN; platonized NC/TMETM). Diagnostic experiments revealed the gross features of the combustion processes. The consistency of the...FLEXIBILITY OF PLASTISOL DOUBLE BASE PROPELLANTS" N. Kubota, T. J. Ohlemiller, L. H. Caveny and M. Summerfield Proceedings of Tenth International Symposium...filled nitrocellulose (NC) and trimethylolethane trinitrate (MTN) plastisols manufactured in conventional vertical mixers. They have the important

  12. The recipient's heme oxygenase-1 promoter region polymorphism is associated with cardiac allograft vasculopathy.

    PubMed

    Freystaetter, Kathrin; Andreas, Martin; Bilban, Martin; Perkmann, Thomas; Kaider, Alexandra; Masetti, Marco; Kocher, Alfred; Wolzt, Michael; Zuckermann, Andreas

    2017-02-10

    Heme oxygenase-1 (HO-1) catalyses the degradation of heme to biliverdin, free iron, and carbon monoxide. The promoter region contains a highly polymorphic (GT)n repeat, where shorter (GT)n repeat sequences are linked to higher transcriptional activity, which was shown to correlate with a cytoprotective effect. Higher HO-1 levels may protect from cardiac allograft vasculopathy. Cardiac allograft recipients transplanted between 1988 and 2012 were analyzed for the HO-1 (GT)n repeat polymorphism using PCR and DNA fragment analysis with capillary electrophoresis. A relation to cardiac allograft vasculopathy (CAV) was analyzed using Cox regression including common risk factors for CAV and the occurrence of rejection episodes as explanatory variables. A total of 344 patients were analyzed, of which 127 patients were positive for CAV (36.9%). In our multivariable Cox regression analysis, the short homozygous HO-1 (GT)n genotype with <27 repeats (S/S) revealed a higher risk for CAV (P = 0.032). Donor age (P = 0.001) and donor weight (P = 0.005) were significant predictors for CAV. A potential risk for CAV was associated with rejection episodes (P = 0.058) and history of smoking (P = 0.06). The recipient HO-1 (GT)n genotype may contribute to CAV development. This finding has to be evaluated in larger series including studies targeting the underlying disease mechanism.

  13. Effect of ethacrynic acid, a glutathione-S-transferase inhibitor, on nitroglycerin-mediated cGMP elevation and vasorelaxation of rabbit aortic strips.

    PubMed

    Kenkare, S R; Benet, L Z

    1993-07-20

    The effects of ethacrynic acid (ECA), an inhibitor of glutathione-S-transferase, on both the pharmacologic and biochemical responses of aortic tissue to nitroglycerin (GTN) were evaluated. Using the rabbit aortic strip model, relaxation responses to 0.6 microM GTN were measured with and without ECA (0.2 mM) pretreatment. These same strips were frozen, and the concentrations of cGMP in the strips were measured using a 3H-labeled radioimmunoassay. Both the relaxation response and the increase in cGMP upon GTN treatment were reduced significantly by pretreatment of the strips with ECA. A correlation was observed between the decreases in the pharmacodynamic and biochemical responses upon ECA pretreatment. cGMP levels in strips treated with sodium nitroprusside, which generates nitric oxide by mechanisms distinct from that for organic nitrates, were not decreased by ECA pretreatment. These observations suggest that the mechanism of GTN action involves a glutathione-S-transferase-mediated metabolic step for GTN and that the isozyme(s) involved in this activation process may be inhibited by ECA.

  14. Application of Gurson-Tvergaard-Needleman constitutive model to the tensile behavior of reinforcing bars with corrosion pits.

    PubMed

    Xu, Yidong; Qian, Chunxiang

    2013-01-01

    Based on meso-damage mechanics and finite element analysis, the aim of this paper is to describe the feasibility of the Gurson-Tvergaard-Needleman (GTN) constitutive model in describing the tensile behavior of corroded reinforcing bars. The orthogonal test results showed that different fracture pattern and the related damage evolution process can be simulated by choosing different material parameters of GTN constitutive model. Compared with failure parameters, the two constitutive parameters are significant factors affecting the tensile strength. Both the nominal yield and ultimate tensile strength decrease markedly with the increase of constitutive parameters. Combining with the latest data and trial-and-error method, the suitable material parameters of GTN constitutive model were adopted to simulate the tensile behavior of corroded reinforcing bars in concrete under carbonation environment attack. The numerical predictions can not only agree very well with experimental measurements, but also simplify the finite element modeling process.

  15. Application of Gurson–Tvergaard–Needleman Constitutive Model to the Tensile Behavior of Reinforcing Bars with Corrosion Pits

    PubMed Central

    Xu, Yidong; Qian, Chunxiang

    2013-01-01

    Based on meso-damage mechanics and finite element analysis, the aim of this paper is to describe the feasibility of the Gurson–Tvergaard–Needleman (GTN) constitutive model in describing the tensile behavior of corroded reinforcing bars. The orthogonal test results showed that different fracture pattern and the related damage evolution process can be simulated by choosing different material parameters of GTN constitutive model. Compared with failure parameters, the two constitutive parameters are significant factors affecting the tensile strength. Both the nominal yield and ultimate tensile strength decrease markedly with the increase of constitutive parameters. Combining with the latest data and trial-and-error method, the suitable material parameters of GTN constitutive model were adopted to simulate the tensile behavior of corroded reinforcing bars in concrete under carbonation environment attack. The numerical predictions can not only agree very well with experimental measurements, but also simplify the finite element modeling process. PMID:23342140

  16. Effect of heme oxygenase-1 gene promoter polymorphism on cancer risk by histological subtype: A prospective study in arseniasis-endemic areas in Taiwan.

    PubMed

    Wu, Meei-Maan; Lee, Chih-Hung; Hsu, Ling-I; Cheng, Wen-Fang; Lee, Te-Chang; Wang, Yuang-Hung; Chiou, Hung-Yi; Chen, Chien-Jen

    2016-04-15

    Heme oxygenase (HO)-1 is upregulated by many stressful stimuli, including arsenic. A GT-repeat ((GT)n) polymorphism in the HO-1 gene promoter inversely modulates the levels of HO-1 induction. Previous HO-1 (GT)n polymorphism studies in relation to cancer risk have shown disparate results. We prospectively investigated the associations between HO-1 (GT)n polymorphism and cancer risk related to arsenic from drinking water. Totally, 1,013 participants from community-based cohorts of arseniasis-endemic areas in Taiwan were followed for 13 years. Allelic polymorphisms were classified into long (L, ≥ 27 (GT)n) and short (S, <27 (GT)n). Newly developed cases were identified through linkage with National Cancer Registry of Taiwan. Multivariate Cox proportional hazard methods were used to evaluate effects of the HO-1 polymorphism alone or combined with arsenic exposure. Results showed that participants with the S/S genotype had an increased risk of Bowen's disease (HR = 10.49; 95% CI: 2.77-39.7), invasive skin cancer (HR = 2.99; 95% CI: 1.13-7.87), and lung squamous cell carcinoma (HR = 3.39; 95% CI: 1.15-9.95) versus those with L/S or L/L genotype. The S/S genotype combined with high arsenic exposure (>300 μg/L) had a greater risk of skin cancer compared to the genotype alone. Consistent with previous findings, participants with the S-allele had a reduced risk of lung adenocarcinoma (HR = 0.21; 95% CI: 0.03-0.68) versus those with L/L genotype. There were no significant differences in risk of urothelial carcinoma among the three genotypes. Associations of HO-1 (GT)n polymorphism with cancer risk differs by histological subtype and the polymorphism should be considered a modifier in the risk assessment of arsenic exposure.

  17. Metabolic Engineering of Plants to Produce Precursors (Phloroglucinol and 1,2,4-butanetriol) of Energetic Materials

    DTIC Science & Technology

    2015-01-02

    Precursors (Phloroglucinol and 1,2,4-butanetriol) of Energetic Materials 5a. CONTRACT NUMBER 5b. GRANT NUMBER N000140810470 5c. PROGRAM...phloroglucinol, which are precursors of energetic materials butanetriol trinitrate (BTTN) and l,3,5-triamino-2,4,6 trinitrobenzene (TATB), respectively, in...energetic materials in plants overcomes many problems associated with the current chemical-based methods. Bacterial synthesis of butanetriol from xylose or

  18. Modeling of void coalescence initiation and its impact on the prediction of material failure

    NASA Astrophysics Data System (ADS)

    Msolli, Sabeur; Bettaieb, Mohamed Ben; Abed-Meraim, Farid

    2016-10-01

    In the present paper, Thomason's criterion is coupled with the well-known Gurson-Tvergaard-Needleman (GTN) damage model and used for the determination of the critical void volume fraction fc, which marks the initiation of the coalescence stage. The onset of void coalescence predicted by Thomason's criterion is compared to that obtained by using a predefined fc, which is usually fitted on the basis of experimental results, as originally proposed in the GTN model. Comparisons are made in terms of both single finite element simulations and numerical results of deep drawing of a cup.

  19. The Canoe Ridge Natural Gas Storage Project

    SciTech Connect

    Reidel, Steve P.; Spane, Frank A.; Johnson, Vernon G.

    2003-06-18

    In 1999 the Pacific Gas and Electric Gas Transmission Northwest (GTN) drilled a borehole to investigate the feasibility of developing a natural gas-storage facility in a structural dome formed in Columbia River basalts in the Columbia Basin of south-central Washington State. The proposed aquifer storage facility will be an unconventional one where natural gas will be initially injected (and later retrieved) in one or multiple previous horizons (interflow zones) that are confined between deep (>700 meters) basalt flows of the Columbia River Basalt Group. This report summarizes the results of joint investigations on that feasibility study by GTN and the US Department of Energy.

  20. Choriocarcinoma in Ongoing Pregnancy Presenting with Intracranial Metastasis

    PubMed Central

    Suri, Vanita; Sikka, Pooja; Aggarwal, Neelam; Chopra, Seema

    2016-01-01

    Choriocarcinoma presents usually as persistent trophoblastic disease, with prognosis worsening with duration from antecedent pregnancy. We present a unique case of a woman with choriocarcinoma who presented in the third trimester of pregnancy with eclampsia. She was managed with magnesium sulphate and underwent a caesarean section. However, she developed seizures in the post-partum period that were further investigated and attributed to intracranial metastatic lesions of Gestational Trophoblastic Neoplasia (GTN). We discussed the diagnostic challenge in this rare case of GTN and the grave potential it can have in such a presentation, as in our patient. PMID:28050451

  1. Assessing the Toxicity and Bioavailability of 2,4-Dinitroanisole in Acute and Sub-Chronic Exposures Using the Earthworm, Eisenia fetida

    DTIC Science & Technology

    2010-06-01

    different methods, 2nd method chosen for final study: ► Coelomocytes collected in 2 ml Guaiacol Glyceryl Ether ( GGE ) solution, centrifuged, decanted...worm to GGE t= 2mins collect coelomocyte solution 1 row per worm/treatment, obtain measurements through spectrophotometer NRRT analysis 1) 2) BUILDING

  2. 21 CFR 172.665 - Gellan gum.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....50 gram of sodium chloride is added. The solution is heated to 80 °C with stirring, held at 80 °C for..., sodium, calcium, and magnesium salt. The polysaccharide may contain acyl (glyceryl and acetyl) groups as... bore pipet and transferred into a solution of 10-percent calcium chloride. A tough worm-like gel...

  3. 21 CFR 172.832 - Monoglyceride citrate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION... monooleate and its citric acid monoester manufactured by the reaction of glyceryl monooleate with citric acid... percent-17 percent. (b) It is used, or intended for use, in antioxidant formulations for addition to...

  4. 21 CFR 172.832 - Monoglyceride citrate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.832... manufactured by the reaction of glyceryl monooleate with citric acid under controlled conditions may be safely... use, in antioxidant formulations for addition to oils and fats whereby the additive does not...

  5. 21 CFR 184.1903 - Tributyrin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Substances Affirmed as GRAS § 184.1903 Tributyrin. (a) Tributyrin (C15H26O6, CAS Reg. No. 60-01-5), also known as butyrin or glyceryl tributyrate, is the triester of glycerin and butyric acid. It is prepared by esterification of glycerin with excess butyric acid. (b) The ingredient meets the specification...

  6. 21 CFR 184.1903 - Tributyrin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Substances Affirmed as GRAS § 184.1903 Tributyrin. (a) Tributyrin (C15H26O6, CAS Reg. No. 60-01-5), also known as butyrin or glyceryl tributyrate, is the triester of glycerin and butyric acid. It is prepared by esterification of glycerin with excess butyric acid. (b) The ingredient meets the specification...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed

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

    2016-01-30

    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.

  9. Triploidy—Observations in 154 Diandric Cases

    PubMed Central

    Scholz, Nanna Brink; Bolund, Lars; Nyegaard, Mette; Faaborg, Louise; Jørgensen, Mette Warming; Lund, Helle; Niemann, Isa; Sunde, Lone

    2015-01-01

    Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0–1,4%). PMID:26562155

  10. Triploidy--Observations in 154 Diandric Cases.

    PubMed

    Scholz, Nanna Brink; Bolund, Lars; Nyegaard, Mette; Faaborg, Louise; Jørgensen, Mette Warming; Lund, Helle; Niemann, Isa; Sunde, Lone

    2015-01-01

    Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0-1,4%).

  11. Department of Defense In-Transit Visibility Modifications

    DTIC Science & Technology

    2013-05-23

    14. ABSTRACT Extending operational reach within a Defense Support of Civil Authorities (DSCA) environment demands a comprehensive procurement...VISIBILITY MODIFICATIONS, by Major Charles L. Montgomery, 49 pages. Extending operational reach within a Defense Support of Civil Authorities...GAO U.S. Government Accountability Office GATES Global Air Transportation Execution System GTN Global Transportation Network HD Homeland

  12. Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

    PubMed Central

    Bukhari, Syed Nasir Abbas

    2014-01-01

    The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN) or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2), a natural occurring styryl-lactone. Therefore, it includes (i) the source of GTN and other metabolites; (ii) isolation, purification, and (iii) the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans. PMID:25247178

  13. 77 FR 48132 - Gas Transmission Northwest, LLC; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-13

    ... Energy Regulatory Commission Gas Transmission Northwest, LLC; Notice of Application Take notice that on July 31, 2012, Gas Transmission Northwest, LLC (GTN), filed in Docket No. CP12-494-000, an application... directed to Mr. Richard Parke, Manager, Certificates, Gas Transmission Northwest, LLC, 717 Texas...

  14. Respiratory Toxicology: 1981

    DTIC Science & Technology

    1981-08-01

    therapeutic (vasodilation) effect on angina pectoris (Kalin and Kylin, 1969). It was found that PGDN, EGDN and GTN all were competitive inhibitors of MAO...when expo- sure stops, causes an angina -like effect. In severe cases, vascular spasm may then be followed by death when exposure ceases. Behavorial

  15. EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients.

    PubMed

    Lu, W-G; Ye, F; Shen, Y-M; Fu, Y-F; Chen, H-Z; Wan, X-Y; Xie, X

    2008-01-01

    This study was designed to analyze the outcomes of chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) with EMA-CO regimen as primary and secondary protocol in China. Fifty-four patients with high-risk GTN received 292 EMA/CO treatment cycles between 1996 and 2005. Forty-five patients were primarily treated with EMA-CO, and nine were secondarily treated after failure to other combination chemotherapy. Adjuvant surgery and radiotherapy were used in the selected patients. Response, survival and related risk factors, as well as chemotherapy complications, were retrospectively analyzed. Thirty-five of forty-five patients (77.8%) receiving EMA-CO as first-line treatment achieved complete remission, and 77.8% (7/9) as secondary treatment. The overall survival rate was 87.0% in all high-risk GTN patients, with 93.3% (42/45) as primary therapy and 55.6% (5/9) as secondary therapy. The survival rates were significantly different between two groups (chi(2)= 6.434, P =0.011). Univariate analysis showed that the metastatic site and the number of metastatic organs were significant risk factors, but binomial distribution logistic regression analysis revealed that only the number of metastatic organs was an independent risk factor for the survival rate. No life-threatening toxicity and secondary malignancy were found. EMA-EP regimen was used for ten patients who were resistant to EMA-CO and three who relapsed after EMA-CO. Of those, 11 patients (84.6%) achieved complete remission. We conclude that EMA-CO regimen is an effective and safe primary therapy for high-risk GTN, but not an appropriate second-line protocol. The number of metastatic organs is an independent prognostic factor for the patient with high-risk GTN. EMA-EP regimen is a highly effective salvage therapy for those failing to EMA-CO.

  16. LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

    PubMed Central

    Lertkhachonsuk, Ruangsak; Paiwattananupant, Krissada; Tantbirojn, Patou; Rattanatanyong, Prakasit; Mutirangura, Apiwat

    2015-01-01

    Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN). Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN. Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p = 0.003) and the uCuC of LINE-1 increased in the malignant trophoblast group (p ≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowest p value for distinguishing between the two groups (p < 0.001). The combination of the pretreatment β-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively. Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN. PMID:26448937

  17. Peierls Stress of Dislocations in Molecular Crystal Cyclotrimethylene Trinitramine

    DTIC Science & Technology

    2013-06-04

    inferred from quasi-static simulations. For PRH = 2.14 GPa in a (111) shock, at least five slip systems (with m ≠ 0) remain active. If one considers PRH...1992, 25, 489−496, DOI: 10.1021/ar00023a002. (2) Armstrong, R. W.; Ammon, H . L.; Elban, W. L.; Tsai, D. H . Investigation of Hot-Spot Characteristics...DOI: 10.1063/1.2214639. (5) Cawkwell, M . J.; Ramos, K. J.; Hooks, D. E.; Sewell, T. D. Homogeneous Dislocation Nucleation in Cyclotrimethylene Trinitr

  18. Fluorinated Desensitizing Ingredients for Propellants

    DTIC Science & Technology

    1980-05-24

    Entered) 19. KEY WORDS (Continued) 20 ABSTRACT (Continued) Compound Structure 3-Fluoro-1,2- propanediol dinitrate FCH2CH(ONO2 )CH2ONO2 FDNP 3,3,3...Trifluoro-1,2- propanediol dinitrate F3 CCH(ONO2 )CH2ONO2 TFDNP 4,4,4-Trifluoro-l,2,3-butanetriol F3CCH(ONO 2 )CH(ONO2)CH2ONO 2 Trinitrate TFBTTN Preliminary...are potentially useful propellant ingredients. When compared with 1,2- propanediol dinitrate (DNP), which is currently used in Otto Fuel II, FDNP has a

  19. Clean Manufacture of 2,4,6-Trinitrotoluene (TNT) via Improved Regioselectivity in the Nitration of Toluene

    NASA Astrophysics Data System (ADS)

    Millar, Ross W.; Arber, Anthony W.; Endsor, Robert M.; Hamid, Javid; Eamon Colclough, M.

    2011-04-01

    The U.S. Department of Defense requires an environmentally benign synthesis route to manufacture military grade trinitrotoluene (TNT), which eliminates the production of red water arising from the sulfiting process for removing unsymmetrical trinitrotoluene isomers. We have found that by using a novel nitrating system, N2O5 in dichloromethane, the proportion of metasubstituted nitrotoluenes can be suppressed, and improvements have also been made to the di- and trinitration steps. As a result, TNT with a set point near that of the Mil. Spec. can be made by our process, without the need for sulfite washing; after recrystallization it exceeds the specification.

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

    PubMed

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

    2010-02-22

    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.

  1. The control of ice crystal growth and effect on porous structure of konjac glucomannan-based aerogels.

    PubMed

    Ni, Xuewen; Ke, Fan; Xiao, Man; Wu, Kao; Kuang, Ying; Corke, Harold; Jiang, Fatang

    2016-11-01

    Konjac glucomannan (KGM)-based aerogels were prepared using a combination of sol-gel and freeze-drying methods. Preparation conditions were chosen to control ice crystal growth and aerogel structure formation. The ice crystals formed during pre-freezing were observed by low temperature polarizing microscopy, and images of aerogel pores were obtained by scanning electron microscopy. The size of ice crystals were calculated and size distribution maps were drawn, and similarly for aerogel pores. Results showed that ice crystal growth and aerogel pore sizes may be controlled by varying pre-freezing temperatures, KGM concentration and glyceryl monostearate concentration. The impact of pre-freezing temperatures on ice crystal growth was explained as combining ice crystal growth rate with nucleation rate, while the impacts of KGM and glyceryl monostearate concentration on ice crystal growth were interpreted based on their influences on sol network structure.

  2. Electrochemical characterization of bilayer lipid membrane-semiconductor junctions

    SciTech Connect

    Zhao, Xiao Kang; Baral, S.; Fendler, J.H. )

    1990-03-08

    Three different systems of glyceryl monooleate (GMO), bilayer lipid membrane (BLM) supported semiconductor particles have been prepared and characterized. A single composition of particulate semiconductor deposited only on one side of the BLM constituted system A, two different compositions of particulate semiconductors sequentially deposited on the same side of the BLM represented system B, and two different compositions of particulate semiconductors deposited on the opposite sides of the BLM made up system C.

  3. Automated Nitrocellulose Analysis

    DTIC Science & Technology

    1978-12-01

    is acceptable. (4) As would be expected from the theory of osmosis , a high saline content in the dialysis recipient stream (countersolution) is of...Block 39, II different from Report; IS. SUPPLEMENTARY NOTES IS. KEY WOROS (Continue on rereri Analysis Automated analysis Dialysis Glyceryl...Technicon AutoAnalyzer, involves aspiration of a stirred nitrocellulose suspension, dialysis against 9 percent saline, and hydrolysis with 5N sodium

  4. 21 CFR 184.1901 - Triacetin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Triacetin. 184.1901 Section 184.1901 Food and....1901 Triacetin. (a) Triacetin (C8 H14O6, CAS Reg. No. 102-76-1), also known as 1,2,3,-propanetriol triacetate or glyceryl triacetate, is the triester of glycerin and acetic acid. Triacetin can be prepared...

  5. Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells.

    PubMed

    Brenneman, D E; Spector, A A

    1974-07-01

    Much of the lipid present in the ascites plasma in which Ehrlich cells grow is contained in very low density lipoproteins (VLDL). Chemical measurements indicated that triglycerides were taken up by the cells during in vitro incubation with ascites VLDL. When tracer amounts of radioactive triolein were incorporated into the ascites VLDL, the percentage uptakes of glyceryl tri[1-(14)C]oleate and triglycerides measured chemically were similar. The cells also took up [2-(3)H]glyceryl trioleate that was added to VLDL, but the percentage of available (3)H recovered in the cell lipids was 30-40% less than that of (1 4)C from glyceryl tri[1-(1 4)C]oleate. This difference was accounted for by water-soluble (3)H that accumulated in the incubation medium, suggesting that extensive hydrolysis accompanied the uptake of VLDL triglycerides. Radioactive fatty acids derived from the VLDL triglycerides were incorporated into cell phospholipids, glycerides, and free fatty acids, and they also were oxidized to CO(2). Triglyceride utilization increased as the VLDL concentration was raised. These results suggest that one function of the ascites plasma VLDL may be to supply fatty acid to the Ehrlich cells and that the availability of fatty acid to this tumor is determined in part by the ascites plasma VLDL concentration. Although Ehrlich cells incorporate almost no free glycerol into triglycerides, considerable amounts of [2-(3)H]glyceryl trioleate radioactivity were recovered in cell triglycerides. This indicates that at least some VLDL triglycerides were taken up intact. The net uptake of VLDL protein and cholesterol was very small relative to the triglyceride uptake, suggesting that intact triglycerides are transferred from the ascites VLDL to the Ehrlich cells and that hydrolysis occurs after the triglyceride is associated with the cells.

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

    PubMed Central

    Tommasi, Immacolata; Fusco, Caterina

    2013-01-01

    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. PMID:24163617

  7. Unusual Presentation of Hypothyroidism in a Pregnant Woman, Mimicking Gestational Trophoblastic Neoplasm

    PubMed Central

    Aminimoghaddam, Soheila; Mazloomi, Maryam; Rahimi, Maryam

    2016-01-01

    Hypothyroidism is a common health issue worldwide with varying clinical manifestations. We report a woman who experienced an incomplete abortion and undiagnosed hypothyroidism who was referred to the oncologist with the suspicion of metastatic gestational trophoblastic neoplasm (GTN). A 29-year-old woman with incomplete abortion was referred to an oncologist for possible GTN due to persistent active vaginal bleeding, an elevated beta human chorionic gonadotropin (hCG), abnormal cervical inspection exam, abnormal liver function tests, ovarian enlargement, ascites, and a pleural effusion. She was found to have hypothyroidism in further work-up. She was managed with thyroid hormone replacement therapy and her condition improved after 6 weeks. Complete resolution of the ovarian mass and pericardial and pleural effusion was achieved. This case describes an important experience; hypothyroidism should be considered in the differential diagnosis of any woman with an incomplete abortion presenting with an ovarian mass. Evaluation and correct diagnosis are important to prevent mismanagement. PMID:27034864

  8. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

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

    PubMed

    Wang, L L; Johnson, E A

    1992-02-01

    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.

  10. Characterization of semi-solid Self-Emulsifying Drug Delivery Systems (SEDDS) of atorvastatin calcium by Raman image spectroscopy and chemometrics.

    PubMed

    Breitkreitz, Márcia C; Sabin, Guilherme P; Polla, Griselda; Poppi, Ronei J

    2013-01-25

    A methodology based on Raman image spectroscopy and chemometrics for homogeneity evaluation of formulations containing atorvastatin calcium in Gelucire(®) 44/14 is presented. In the first part of the work, formulations with high amounts of Gelucire(®) 44/14 (80%) and solvents of different polarities (diethylene glycol monoethyl ether, propyleneglycol, propylene glycol monocaprylate and glyceryl mono/dicaprylate/caprate) were prepared for miscibility screening evaluation by classical least squares (CLS). It was observed that Gelucire(®) 44/14 presented higher affinity for the lipophilic solvents glyceryl mono/dicaprylate/caprate and propylene glycol monocaprylate, whose samples were observed to be homogeneous, and lower affinity for the hydrophilic solvents diethylene glycol monoethyl ether and propyleneglycol, whose samples were heterogeneous. In the second part of the work, the ratio of glyceryl mono/dicaprylate/caprate and Gelucire(®) 44/14 was determined based on studies in water and allowed the selection of the proportions of these two excipients in the preconcentrate that provided supersaturation of atorvastatin upon dilution. The preconcentrate was then evaluated for homogeneity by partial least squares (PLS) and an excellent miscibility was observed in this proportion as well. Therefore, it was possible to select a formulation that presented simultaneously homogeneous preconcentrate and solubility enhancement in water by Raman image spectroscopy and chemometrics.

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

    PubMed

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

    2012-01-01

    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.

  12. Intransit Visibility: Capturing All the Source Data.

    DTIC Science & Technology

    1996-05-01

    was abandoned for apush system. Now with version 2.3, participating systems push information to an integrated database, which allows GTN to support a...Transportation (HOST) and the Global Decision Support System (GDSS). PRAMS "records non-unit passenger reservations, issues boarding passes, and generates...the terms of sale are free-on- board (FOB) destination (DoD, 1995: 3-15). Under FOB destination, the vendor delivers goods to a location specified by

  13. The Lack of a Designated National In-Transit Visibility System Affects the Synchronization of Information Sharing and the Timely Distribution of Materials during Natural Disaster Efforts

    DTIC Science & Technology

    2010-06-11

    Global Command and Communication System GTN Global Transportation Network HUD Housing and Urban Division IG Inspector General IRRIS Intelligent...outcome will most likely produce new policies and procedures. Today, the synchronization, collaboration and integration of natural disasters extend ...and performs.” 15 In order to combat some of its logistical challenges, FEMA redesigned the LMD with the intent to model “Department of Defense

  14. Army Battlefield Distribution Through the Lens of OIF: Logical Failures and the Way Ahead

    DTIC Science & Technology

    2007-11-02

    without adequate regard for examining the battlefield effectiveness of such a business-oriented model . Clausewitz wrote in Book Two, Chapter One of...make the systems in use more efficient on the model of industry, unfortunately a more efficient system served only to treat a symptom of the underlying...transportation network ( GTN ) and create a single data warehouse that operational and tactical distribution managers will be able to use in order to meet

  15. War in the Information Age: A Primer for Cyberspace Operations in 21st Century Warfare

    DTIC Science & Technology

    2010-01-01

    undertaking, the Soviets needed sophisticated control systems. They bought early model computers on the open market, but when Russian pipeline...whose distinctive and unique character is framed by the use of electronics and the electromagnetic spectrum to create, store, modify , exchange, and...GCCS), Global Transportation Network ( GTN ), In-Transit Visibility (ITV), Joint Tactical Radio System (JTRS), Blue Force Tracker (BFT), Theater Battle

  16. Aeromedical Evacuation: Validating Civil Reserve Air Fleet

    DTIC Science & Technology

    2009-02-25

    Requirements Center GTN Global Transportation Network xiii IAT.R 0554 GWOT Global War on Terrorism HDPLP High Deck Patient Lift Platform HLS homeland...the requirements against a PACOM plan and/or modify the program. The past several years, USTRANSCOM SG has been unsuccessful in obtaining CRAF AE...flight on September 15, 1991, and the first production model was delivered to Charleston Air Force Base, South Carolina June 14, 1993. The aircraft can

  17. The Battle Command Sustainment Support System: The Army’s Command and Control System for Logistics

    DTIC Science & Technology

    2009-05-21

    a different system to fill the void. Tapestry Industries of San Diego, CA developed the Joint Deployment Logistics Model (JDLM) for Army simulation...strategic to the tactical level and all on a graphic display the operator can modify to meet the commander’s specific requirements. The...electronically uploaded into computer databases such as the Global Transportation Network ( GTN ), the BCS3 can track those shipments projecting and

  18. Uptake and Transformation of the Propellants 2,4-DNT, Perchlorate and Nitroglycerin by Grasses

    DTIC Science & Technology

    2006-07-31

    by performing hydroponic and soil experiments. The propellants 2,4-dinitrotoluene (2,4-DNT), perchlorate and nitroglycerin (GTN) often contaminate...firing ranges due to partially detonated ordnances and incomplete combustion of munitions. In hydroponic experiments, sorption of 2,4-DNT to roots was...and big bluestem (Andropogon gerardii) in the clean-up of propellant contaminated soil was assessed by performing hydroponic and soil experiments. The

  19. Joint Total Asset Visibility A Catalyst for Change in Logistics

    DTIC Science & Technology

    1997-04-01

    was viewed as a force multiplier. On the other hand, when wearing his//her Service or Agency hat, the interviewees, with the exception of the...Operation Desert Shield/Desert Storm, (GPO: 1996), 28-29. 4Colonel Jack Pinnel , “Global Transportation Network: Program Overview & Status Update” , briefing...action officer to the Command’s Crisis Action Team during the Gulf War with later assignment to duty in the GTN office. 5Colonel Jack Pinnel , “Global

  20. Multiple Case Comparison of the In-Transit Visibility Business Process

    DTIC Science & Technology

    2003-03-01

    breakdown in the Air Force “feeder” system. During OEF deployment operations, the Air Force Combat Support Center worked to resolve ITV issues , but was...unsuccessful. After the initial deployment, the Air Staff tasked several agencies to investigate ITV 3 issues (Quinton, 2002). In January 2002, the...and pushed it automatically to GTN.” With modern information technology, these benefits should be easily within grasp. Realizing the benefit

  1. A study on the performance of ductile failure models under different range of stress triaxiality states with experimental validation

    NASA Astrophysics Data System (ADS)

    Amaral, Rui; Teixeira, Pedro; Azinpour, Erfan; Santos, Abel D.; César de Sá, J.

    2016-08-01

    In this work, experimental tests were carried out, under different loading conditions, in order to assess different ductile failure criteria, namely based on GTN, Johnson-Cook or Lemaitre models and to establish new proposals for improvement. Corresponding characterization for damage parameters is performed by an inverse analysis procedure, using reference experimental tests. Numerical simulations of a cross-shaped component are considered for the damage models, and results show a similar trend related with the experimental fracture evidence.

  2. Loglines. September - October 2012

    DTIC Science & Technology

    2012-10-01

    officer, said. To streamline the ordering process, the new toner contract will be available for online ordering and payment via Government Purchase...September - October 2012 Engineering Savings Story by Amanda Neumann T he federal government is one savvy shopper – minus the coupon clipping. Just like...been online that long. “That allows planners to use the data to do analytical studies that could not be done before, because GTN only retained

  3. Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects

    PubMed Central

    Doberer, D; Haschemi, A; Andreas, M; Zapf, T-C; Clive, B; Jeitler, M; Heinzl, H; Wagner, O; Wolzt, M; Bilban, M

    2010-01-01

    BACKGROUND AND PURPOSE Haem oxygenase 1 (HO-1) is an inducible protein that plays a major protective role in conditions such as ischaemia-reperfusion injury and inflammation. In this study, we have investigated the role of haem arginate (HA) in human male subjects in the modulation of HO-1 expression and its correlation with the GT length polymorphism (GTn) in the promoter of the HO-1 gene. EXPERIMENTAL APPROACH In a dose-escalation, randomized, placebo-controlled trial, seven healthy male subjects with a homozygous short (S/S) and eight with a long (L/L) GTn genotype received intravenous HA. HO-1 protein expression and mRNA levels in peripheral blood monocytes, bilirubin, haptoglobin, haemopexin and haem levels were analysed over a 48 h observation period. KEY RESULTS We found that the baseline mRNA levels of HO-1 were higher in L/L subjects, while protein levels were higher in S/S subjects. HA induced a dose-dependent increase in the baseline corrected area under the curve values of HO-1 mRNA and protein over 48 h. The response of HO-1 mRNA was more pronounced in L/L subjects but the protein level was similar across the groups. CONCLUSIONS AND IMPLICATION HA is an effective inducer of HO-1 in humans irrespective of the GTn genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials. PMID:20718734

  4. GT microsatellite repeats in the heme oxygenase-1 gene promoter associated with abdominal aortic aneurysm in Croatian patients.

    PubMed

    Gregorek, Andrea Crkvenac; Gornik, Kristina Crkvenac; Polancec, Darija Stupin; Dabelic, Sanja

    2013-06-01

    Abdominal aortic aneurysm (AAA) is a complex genetic disorder caused by the interplay of genetic and environmental risk factors. The number of (GT)(n) repeats in the heme oxygenase-1 (HO-1) gene promoter modulates transcription of this enzyme, which might have anti-inflammatory, antioxidant, antiapoptotic, and antiproliferative effect. The distribution of alleles and genotypes in Croatian individuals genotyped for the (GT)(n) HO-1 polymorphism was similar to that in other European populations. Frequency of the short (S) alleles (GT < 25) was higher in AAA patients (41.9%) than in non-AAA individuals (28.2%, p = 0.0026) because there were more SL heterozygotes among the AAA patients. The SL genotype appeared to increase the risk for AAA, but the increase was not statistically significant after adjustment for age, sex, smoking, hypertension, and hyperlipidemia (OR = 1.53, 95% CI 0.90-3.09, p = 0.062). These findings contradict those of the only other study performed so far on the association of (GT)(n) HO-1 polymorphism and AAA.

  5. Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms.

    PubMed

    Agnew, C E; Rea, D J; McCann, A J; Lockhart, C J; Hamilton, P K; Quinn, C E; McVeigh, G E; McGivern, R C

    2009-09-01

    Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p<0.00001) and between GTN and non-GTN test states (p=0.0002).

  6. Ductile fracture model in the shearing process of zircaloy sheet for nuclear fuel spacer grids

    NASA Astrophysics Data System (ADS)

    Wang, Jaeyoon; Kim, Naksoo; Lee, Hyungyil

    2012-04-01

    Features of sheared edges are predicted based on material properties of Zircaloy obtained from the tensile test and ductile fracture model such as the Gurson-Tvergaard-Needleman (GTN) and Johnson-Cook models. The sheared edges formations are numerically analyzed in each ductile model. An appropriate ductile fracture model is selected to study the relative depth of sheared edges with respect to process parameters. The tendency of failure parameters that are affected by sheared edges and fracture duration is investigated. We applied changes on parameters of failure models to show that the punch force curve and the ratio of characteristic lengths could be coincided, which led us to conclude that the GTN and Johnson-Cook models are equivalent. In the Johnson-Cook model, however, the characteristic length of the sheared edges does not change as each failure parameter reaches a critical value. Hence, the FE prediction model for forming defects is developed using the GTN failure model. Finally, the characteristic length of sheared edges have been measured using the FE prediction model for shearing process parameters such as punch velocities, clearance, and tool wear. Our results showed that the punch-die clearance is the most significant factor that affects forming defects when compared to other factors.

  7. Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

    PubMed

    Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

    2014-12-01

    Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important.

  8. Photoerasing paper and thermocoloring film

    NASA Astrophysics Data System (ADS)

    Kanakkanatt, Sebastian V.

    1997-08-01

    Thermal coloration of spiropyrans and spiroxazines at or above their melting point is well known to photochromists. The erasure of the color developed by exposure of photochromic paper by radiations of certain wavelengths in the visible region is little known. Six-nitrospirobenzopyran and 8- nitrospirobenzopyran, 8-methoxy-6-nitrospirobenzo-pyran, 6- methoxy-8-nitrospirobenzopyran, and 6,8-dinitrospirobenzopyran have been studied. The medium in which these photochromic dyes were dissolved or incorporated was limited to cellulose derivatives such as cellulose acetate, cellulose acetate- butyrate, and cellulose trinitrate. Paper coated with 6- nitrospirobenzopyran dissolved in an ethyl acetate solution of cellulose trinitrate readily colored on exposure to UV light or IR radiation and faded on exposure to light in the visible range. This unusual phenomenon, although not fully understood, is believed to be a selective light sensitizing ability of nitro groups. The applications of photoerasing paper and thermally colorable films are numerous, such as in polaroid type photography, in copy machines, and in thermally stable photochromic ophthalmic lenses.

  9. The Global Terrestrial Network for Permafrost Database: metadata statistics and prospective analysis on future permafrost temperature and active layer depth monitoring site distribution

    NASA Astrophysics Data System (ADS)

    Biskaborn, B. K.; Lanckman, J.-P.; Lantuit, H.; Elger, K.; Streletskiy, D. A.; Cable, W. L.; Romanovsky, V. E.

    2015-03-01

    The Global Terrestrial Network for Permafrost (GTN-P) provides the first dynamic database associated with the Thermal State of Permafrost (TSP) and the Circumpolar Active Layer Monitoring (CALM) programs, which extensively collect permafrost temperature and active layer thickness data from Arctic, Antarctic and Mountain permafrost regions. The purpose of the database is to establish an "early warning system" for the consequences of climate change in permafrost regions and to provide standardized thermal permafrost data to global models. In this paper we perform statistical analysis of the GTN-P metadata aiming to identify the spatial gaps in the GTN-P site distribution in relation to climate-effective environmental parameters. We describe the concept and structure of the Data Management System in regard to user operability, data transfer and data policy. We outline data sources and data processing including quality control strategies. Assessment of the metadata and data quality reveals 63% metadata completeness at active layer sites and 50% metadata completeness for boreholes. Voronoi Tessellation Analysis on the spatial sample distribution of boreholes and active layer measurement sites quantifies the distribution inhomogeneity and provides potential locations of additional permafrost research sites to improve the representativeness of thermal monitoring across areas underlain by permafrost. The depth distribution of the boreholes reveals that 73% are shallower than 25 m and 27% are deeper, reaching a maximum of 1 km depth. Comparison of the GTN-P site distribution with permafrost zones, soil organic carbon contents and vegetation types exhibits different local to regional monitoring situations on maps. Preferential slope orientation at the sites most likely causes a bias in the temperature monitoring and should be taken into account when using the data for global models. The distribution of GTN-P sites within zones of projected temperature change show a high

  10. Internationally coordinated glacier monitoring - a timeline since 1894

    NASA Astrophysics Data System (ADS)

    Nussbaumer, Samuel U.; Armstrong, Richard; Fetterer, Florence; Gärtner-Roer, Isabelle; Hoelzle, Martin; Machguth, Horst; Mölg, Nico; Paul, Frank; Raup, Bruce H.; Zemp, Michael

    2016-04-01

    Changes in glaciers and ice caps provide some of the clearest evidence of climate change, with impacts on sea-level variations, regional hydrological cycles, and natural hazard situations. Therefore, glaciers have been recognized as an Essential Climate Variable (ECV). Internationally coordinated collection and distribution of standardized information about the state and change of glaciers and ice caps was initiated in 1894 and is today organized within the Global Terrestrial Network for Glaciers (GTN-G). GTN-G ensures the continuous development and adaptation of the international strategies to the long-term needs of users in science and policy. A GTN-G Steering Committee coordinates, supports and advices the operational bodies responsible for the international glacier monitoring, which are the World Glacier Monitoring Service (WGMS), the US National Snow and Ice Data Center (NSIDC), and the Global Land Ice Measurements from Space (GLIMS) initiative. In this presentation, we trace the development of the internationally coordinated glacier monitoring since its beginning in the 19th century. Today, several online databases containing a wealth of diverse data types with different levels of detail and global coverage provide fast access to continuously updated information on glacier fluctuation and inventory data. All glacier datasets are made freely available through the respective operational bodies within GTN-G, and can be accessed through the GTN-G Global Glacier Browser (http://www.gtn-g.org/data_browser.html). Glacier inventory data (e.g., digital outlines) are available for about 180,000 glaciers (GLIMS database, RGI - Randolph Glacier Inventory, WGI - World Glacier Inventory). Glacier front variations with about 45,000 entries since the 17th century and about 6,200 glaciological and geodetic mass (volume) change observations dating back to the 19th century are available in the Fluctuations of Glaciers (FoG) database. These datasets reveal clear evidence that

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

    PubMed

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

    2014-01-01

    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.

  12. Holographic interferometry of ultrasmall-pressure-induced curvature changes of bilayer lipid membranes

    SciTech Connect

    Picard, G.; Schneider-Henriquez, J.E.; Fendler, J.H. )

    1990-01-25

    Two-exposure interferometric holograms have been shown to sensitively report ultrasmall-pressure (10 natm)-induced curvature changes in glyceryl monooleate (GMO) bilayer lipid membranes (BLMs). The number of concentric fringes observed, and hence the lateral distance between the plane of the Teflon and the BLM, increased linearly with increasing transmembrane pressure and led to a value of 1.1 {plus minus} 0.05 dyn/cm for the surface tension of the BLM. BLMs with appreciable Plateau-Gibbs borders have been shown to undergo nonuniform deformation; the bilayer portion is distorted less than the surrounding Plateau-Gibbs border upon the application of a transmembrane pressure gradient.

  13. High-resolution proton nuclear magnetic resonance characterization of seminolipid from bovine spermatozoa.

    PubMed

    Alvarez, J G; Storey, B T; Hemling, M L; Grob, R L

    1990-06-01

    The high-resolution one- and two-dimensional proton nuclear magnetic resonance (1H-NMR) characterization of seminolipid from bovine spermatozoa is presented. The 1H-NMR data was confirmed by gas-liquid chromatography-mass spectrometric analysis of the partially methylated alditol acetates of the sugar unit, mild alkaline methanolysis of the glyceryl ester, mobility on normal phase and diphasic thin-layer chromatography (HPTLC), and fast atom bombardment mass spectrometry (FAB-MS). The structure of the molecule corresponds to 1-O-hexadecyl-2-O-hexadecanoyl-3-O-beta-D-(3'-sulfo)-galactopyranosyl- sn-glycerol.

  14. Aerobic Degradation of 2,4,6-Trinitrotoluene by Enterobacter cloacae PB2 and by Pentaerythritol Tetranitrate Reductase

    PubMed Central

    French, Christopher E.; Nicklin, Stephen; Bruce, Neil C.

    1998-01-01

    Enterobacter cloacae PB2 was originally isolated on the basis of its ability to utilize nitrate esters, such as pentaerythritol tetranitrate (PETN) and glycerol trinitrate, as the sole nitrogen source for growth. The enzyme responsible is an NADPH-dependent reductase designated PETN reductase. E. cloacae PB2 was found to be capable of slow aerobic growth with 2,4,6-trinitrotoluene (TNT) as the sole nitrogen source. Dinitrotoluenes were not produced and could not be used as nitrogen sources. Purified PETN reductase was found to reduce TNT to its hydride-Meisenheimer complex, which was further reduced to the dihydride-Meisenheimer complex. Purified PETN reductase and recombinant Escherichia coli expressing PETN reductase were able to liberate nitrogen as nitrite from TNT. The ability to remove nitrogen from TNT suggests that PB2 or recombinant organisms expressing PETN reductase may be useful for bioremediation of TNT-contaminated soil and water. PMID:9687442

  15. Aerobic degradation of 2,4,6-trinitrotoluene by Enterobacter cloacae PB2 and by pentaerythritol tetranitrate reductase

    SciTech Connect

    French, C.E.; Bruce, N.C.; Nicklin, S.

    1998-08-01

    Enterobacter cloacae PB2 was originally isolated on the basis of its ability to utilize nitrate esters, such as pentaerythritol tetranitrate (PETN) and glycerol trinitrate, as the sole nitrogen source for growth. The enzyme responsible is an NADPH-dependent reductase designated PETN reductase. E. cloacae PB2 was found to be capable of slow aerobic growth with 2,4,6-trinitrotoluene (TNT) as the sole nitrogen source. Dinitrotoluenes were not produced and could not be used as nitrogen sources. Purified PETN reductase was found to reduce TNT to its hydride-Meisenheimer complex, which was further reduced to the dihydride-Meisenheimer complex. Purified PETN reductase and recombinant Escherichia coli expressing PETN reductase were able to liberate nitrogen as nitrite from TNT. The ability to remove nitrogen from TNT suggests that PB2 or recombinant organisms expressing PETN reductase may be useful for bioremediation of TNT-contaminated soil and water.

  16. [New perspectives for an old problem: premature labor].

    PubMed

    Barrón Vallejo, J; Kably Ambe, A; Limón Luque, L; Barroso Villa, G; Jurado Jurado, M; Blank Goldenberg, C

    1997-08-01

    Preterm birth has been and continues to be one of the most serious problems in Obstetrics. It is the most common cause of neonatal death, and morbidity in surviving infants. The presence of bacterial vaginosis, and other genital infections is associated with increased risk of preterm labor. Cytokines promote the release of prostaglandin, and have been implicated as cause of uterina activity. Recently, new methods of detection as transvaginal ultrasonography, and measures of cervical fetal fibronectin have been acclaimed as useful to detect the problem. Atosiban, cytokines, glyceril trinitrate, and many others agents have been proposed as treatments and are under investigation. Such drugs, will allow an effective management of preterm labor with lower side effects. Antenatal TRH administration cannot be recommended for widespread clinical use. However, the antenatal administration of corticosteroids to fetuses at risk of preterm delivery include not only a reduction in the risk of respiratory distress syndrome but also a significative reduction in intraventricular hemorrhage mortality.

  17. Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar Pregnancy

    PubMed Central

    Hasanzadeh, Malihe; Sharifi, Norrie; Farazestanian, Marjaneh; Nazemian, Seyed Saman; Madani Sani, Faezeh

    2016-01-01

    Background Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies. Objectives In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy. Patients and Methods In a prospective cross sectional study by using a high accuracy technique EnVision Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls. Results We studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%. Conclusions Our data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages. PMID:27703642

  18. Advancing global hydro-climatological data archives to support climate change impact assessments on water resources

    NASA Astrophysics Data System (ADS)

    Saile, P.

    2012-12-01

    Climate variations and changing climate will very likely alter the rate and nature of hydrological processes and consequently affect water resources in many regions. Current General Circulation Models and downscaling methods that are increasingly used to assess changes in the water cycle and water resource vulnerabilities introduce a cascade of uncertainties that cannot realistically be dealt with at the moment and are too inaccurate to support improved decision-making for water management and for future water systems design. Therefore, water managers need not only improved hydrological and climate modelling and downscaling methods but also access to adequate hydro-meteorological monitoring networks. The Global Terrestrial Network for Hydrology (GTN-H), a joint effort by the World Meteorological Organization (WMO) and several global observing systems, aims at integrating in-situ and remote sensing hydrological observations with hydrological model results held by its partner institutions to support a wide range of hydrological applications including research of global and regional climate change. Adhering to the different needs of all data users (scientists, policy makes and other stakeholders) and bridging the gap between the distributed datasets, currently a new information system is being developed to enable web-based discovery, access and analysis of observation data and derived products served through GTN-H. This system is built on international standards published by the Open Geospatial Consortium (OGC) using open standardized web services, namely (1) Catalogue Services for data discovery, (2) Web Map Services for data visualization and (3) Web Feature Services, Web Coverage Services and Sensor Observation Services for data access. This presentation will give an overview about the GTN-H data archive and the design of the new information system including an outlook of its potential use for water related climate change impact assessments.

  19. Alcohol acutely increases vascular reactivity together with insulin sensitivity in type 2 diabetic men.

    PubMed

    Schaller, G; Kretschmer, S; Gouya, G; Haider, D G; Mittermayer, F; Riedl, M; Wagner, O; Pacini, G; Wolzt, M; Ludvik, B

    2010-01-01

    Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.

  20. Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial dysfunction.

    PubMed

    Mittermayer, Friedrich; Pleiner, Johannes; Schaller, Georg; Zorn, Stefan; Namiranian, Khodadad; Kapiotis, Stylianos; Bartel, Gregor; Wolfrum, Mathias; Brügel, Mathias; Thiery, Joachim; Macallister, Raymond J; Wolzt, Michael

    2005-10-01

    Acute inflammation causes endothelial dysfunction, which is partly mediated by oxidant stress and inactivation of nitric oxide. The contribution of depletion of tetrahydrobiopterin (BH(4)), the cofactor required for nitric oxide generation, is unclear. In this randomized, double-blind, three-way crossover study, forearm blood flow (FBF) responses to ACh and glyceryltrinitrate (GTN) were measured before and 3.5 h after infusion of Escherichia coli endotoxin (LPS, 20 IU/kg iv) in eight healthy men. The effect of intra-arterial BH(4) (500 microg/min), placebo, or vitamin C (24 mg/min) was studied on separate days 3.5 h after LPS infusion. In addition, human umbilical vein endothelial cells were incubated for 24 h with vitamin C and LPS. ACh and GTN caused dose-dependent forearm vasodilation. The FBF response to ACh, which was decreased by 23 +/- 17% (P < 0.05) by LPS infusion, was restored to baseline reactivity by BH(4) and vitamin C. FBF responses to GTN were not affected by BH(4) or vitamin C. LPS increased leukocyte count, high-sensitivity C-reactive protein, IL-6, IL-1beta, IFN-gamma, monocyte chemoattractant protein-1, pulse rate, and body temperature and decreased platelet count and vitamin C concentration. Vitamin C increased forearm plasma concentration of BH(4) by 32% (P < 0.02). Incubation with LPS and vitamin C, but not LPS alone, increased intracellular BH(4) concentration in human umbilical vein endothelial cells. Impaired endothelial function during acute inflammation can be restored by BH(4) or vitamin C. Vitamin C may exert some of its salutary effects by increasing BH(4) concentration.

  1. Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter.

    PubMed

    Repessé, Yohann; Peyron, Ivan; Dimitrov, Jordan D; Dasgupta, Suryasarathi; Moshai, Elika Farrokhi; Costa, Catherine; Borel-Derlon, Annie; Guillet, Benoit; D'Oiron, Roseline; Aouba, Achille; Rothschild, Chantal; Oldenburg, Johannes; Pavlova, Anna; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2013-10-01

    Induction of heme oxygenase-1, a stress-inducible enzyme with anti-inflammatory activity, reduces the immunogenicity of therapeutic factor VIII in experimental hemophilia A. In humans, heme oxygenase-1 expression is modulated by polymorphisms in the promoter of the heme oxygenase-1-encoding gene (HMOX1). We investigated the relationship between polymorphisms in the HMOX1 promoter and factor VIII inhibitor development in severe hemophilia A. We performed a case-control study on 99 inhibitor-positive patients and 263 patients who did not develop inhibitors within the first 150 cumulative days of exposure to therapeutic factor VIII. Direct sequencing and DNA fragment analysis were used to study (GT)n polymorphism and single nucleotide polymorphisms located at -1135 and -413 in the promoter of HMOX1. We assessed associations between the individual allele frequencies or genotypes, and inhibitor development. Our results demonstrate that inhibitor-positive patients had a higher frequency of alleles with large (GT)n repeats (L: n≥30), which are associated with lesser heme oxygenase-1 expression (odds ratio 2.31; 95% confidence interval 1.46-3.66; P<0.001]. Six genotypes (L/L, L/M, L/S, M/M, M/S and S/S) of (GT)n repeats were identified (S: n<21; M: 21≤n<30). The genotype group including L alleles (L/L, L/M and L/S) was statistically more frequent among inhibitor-positive than inhibitor-negative patients, as compared to the other genotypes (33.3% versus 17.1%) (odds ratio 2.21, 95% confidence interval 1.30-3.76; P<0.01). To our knowledge, this is the first association identified between HMOX1 promoter polymorphism and development of anti-drug antibodies. Our study paves the way towards modulation of the endogenous anti-inflammatory machinery of hemophilia patients to reduce the risk of inhibitor development.

  2. Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components

    PubMed Central

    Martínez-Hernández, Angélica; Córdova, Emilio J.; Rosillo-Salazar, Oscar; García-Ortíz, Humberto; Contreras-Cubas, Cecilia; Islas-Andrade, Sergio; Revilla-Monsalve, Cristina; Salas-Labadía, Consuelo; Orozco, Lorena

    2015-01-01

    Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GT)n and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GT)n polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (<25 GT repeats) of the HMOX1 polymorphism was associated with high systolic and diastolic blood pressure, and the T allele of the NQO1 C609T polymorphism was associated with increased triglyceride levels and decreased HDL-c levels, but only in individuals with MetS. This is the first study to analyse the association between MetS and genes involved in oxidative stress among Mexican Mestizos. Our data suggest that polymorphisms of HMOX1 and NQO1 genes are associated with a high risk of metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals. PMID:25933176

  3. Modeling the ductile fracture and the plastic anisotropy of DC01 steel at room temperature and low strain rates

    NASA Astrophysics Data System (ADS)

    Tuninetti, V.; Yuan, S.; Gilles, G.; Guzmán, C. F.; Habraken, A. M.; Duchêne, L.

    2016-08-01

    This paper presents different extensions of the classical GTN damage model implemented in a finite element code. The goal of this study is to assess these extensions for the numerical prediction of failure of a DC01 steel sheet during a single point incremental forming process, after a proper identification of the material parameters. It is shown that the prediction of failure appears too early compared to experimental results. Though, the use of the Thomason criterion permitted to delay the onset of coalescence and consequently the final failure.

  4. Elastic clearance change in axisymmetric shearing process

    NASA Astrophysics Data System (ADS)

    Yoshida, Yoshinori

    2016-10-01

    An axisymmetric shearing experiment is conducted for a sheet of low carbon steel and stainless steel. Elastic change in the clearance between punch and die is measured. The increase of the clearance in shearing is confirmed and the influence of sheared material's flow stress on the clearance change is shown. Finite element analysis (FEA) of shearing with Gurson-Tvergaard-Needlman model (GTN model) is conducted for shearing of the carbon steels with rigid tools as a numerical experiment. Burr height is predicted in the FEA and the result is compared with the experimental result. In addition, the influence of the clearance on stress state in the material is investigated.

  5. Microsatellite polymorphism in the heme oxygenase-1 promoter is associated with nonsevere and late-onset preeclampsia.

    PubMed

    Kaartokallio, Tea; Klemetti, Miira M; Timonen, Anni; Uotila, Jukka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

    2014-07-01

    Preeclampsia is a serious and phenotypically heterogeneous vascular pregnancy disorder. Heme oxygenase-1 (HO-1) is a stress response enzyme that may protect the maternal endothelium and facilitate adequate metabolic adaptation to pregnancy by its antioxidant and anti-inflammatory functions. HO-1 stress response is modulated by HO-1 gene (HMOX1) polymorphisms. Individuals with the long allele of a guanine-thymine (GTn) microsatellite repeat located in the promoter region of HMOX1 have a higher risk of cardiometabolic diseases compared with those with the short allele. We investigated whether the long GTn allele of HMOX1 is associated with subtypes of preeclampsia. The GTn repeat was genotyped in 759 patients and in 779 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort using DNA fragment analysis. In subtype analyses, the long-long (LL) genotype was associated with nonsevere (additive model: odds ratio [OR], 1.94; 95% confidence interval [CI], 1.13-3.31; recessive model: OR, 1.39; 95% CI, 1.02-1.89) and late-onset (additive model: OR, 1.44; 95% CI, 1.02-2.05; recessive model: OR, 1.28; 95% CI, 1.02-1.59) preeclampsia and with preeclampsia without a small-for-gestational-age infant (recessive model: OR, 1.27; 95% CI, 1.02-1.58). The long allele was associated with nonsevere (OR, 1.35; 95% CI, 1.07-1.70) and late-onset (OR, 1.21; 95% CI, 1.03-1.42) preeclampsia and with preeclampsia without a small-for-gestational-age infant (OR, 1.19; 95% CI, 1.02-1.40). Moreover, both the LL genotype and the long allele were associated with preeclampsia in women who had smoked during pregnancy. In conclusion, the GTn long allele seems to predispose to late-onset, less severe form of preeclampsia. This finding supports the role of HO-1 in the pathogenesis of preeclampsia and suggests that the HO-1 pathway may provide a potential target for the treatment of preeclampsia.

  6. Transgenic Phytoremediation Blasts onto the Scene

    SciTech Connect

    Hooker, Brian S.; Skeen, R S.

    1999-05-01

    The EPA National Priority List contains 22 ammunition production and processing sites that are laden with explosive and propellant wastes. With levels of 2,4,6-trinitrotoluene (TNT) contamination as high as 200 g/kg of solids, some of these sites are literally on the verge of exploding. They also present serious exposure risks to humans and wildlife, as many of these contaminants are also strong toxins and mutagens. In this issue, French et al. describe a new option for cleaning up this dangerous mixture: the use of transgenic plants. They engineered plants to express a bacterial enzyme that can completely denitrify TNT and trinitroglycerin (GTN) into harmless compounds.

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

    SciTech Connect

    Koynova, Rumiana; Tihova, Mariana

    2010-04-12

    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.

  8. Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use

    PubMed Central

    Shin, Chan Young; Kim, Kyu-Bong

    2015-01-01

    Polyethylene glycols (PEGs) are products of condensed ethylene oxide and water that can have various derivatives and functions. Since many PEG types are hydrophilic, they are favorably used as penetration enhancers, especially in topical dermatological preparations. PEGs, together with their typically nonionic derivatives, are broadly utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners. The compounds studied in this review include PEG/PPG-17/6 copolymer, PEG-20 glyceryl triisostearate, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil. Overall, much of the data available in this review are on PEGylated oils (PEG-40 and PEG-60 hydrogenated castor oils), which were recommended as safe for use in cosmetics up to 100% concentration. Currently, PEG-20 glyceryl triisostearate and PEGylated oils are considered safe for cosmetic use according to the results of relevant studies. Additionally, PEG/PPG-17/6 copolymer should be further studied to ensure its safety as a cosmetic ingredient. PMID:26191379

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

    PubMed

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

    2006-09-01

    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.

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

    SciTech Connect

    Mea Cook; Lloyd Keigwin

    2007-11-30

    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.

  11. Microbial Diversity of Cold-Seep Sediments in Sagami Bay, Japan as Determined by 16S rDNA and Lipid Analyses

    NASA Astrophysics Data System (ADS)

    Fang, J.; Arakawa, S.; Kato, C.; Schouten, S.

    2006-12-01

    Microbial communities in Calyptogena sediment and microbial mats of Sagami Bay, Japan were characterized by using 16S rDNA sequencing and lipid biomarker analysis. Characterization of 16S rDNA isolated from these samples suggested a predominance of bacterial phylotypes related to γ- (57-64%) and δ-subclasses (27-29%) of the Proteobacteria. The ɛ-subclass of the Proteobacteria commonly found in cold seeps and hydrothermal vents were only detected in the microbial mat sample. There are significantly different archaeal phylotypes between Calyptogena sediment and microbial mat; the former contains only Crenarchaeota clones (100% of the total archaeal clones) and the latter exclusively Euryarchaeota clones including the ANME-2a and ANME-2c archaeal groups. Many of these lineages are as yet uncultured and undescribed groups of bacteria and archaea. Phospholipid fatty acid analysis suggests the presence of sulfate-reducing and sulfur-oxidizing bacteria. Results of intact glyceryl dialkyl glyceryl tetraether (GDGT) lipid analysis indicate 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.

  12. Fatty Acid Ethyl Esters Are Less Toxic Than Their Parent Fatty Acids Generated during Acute Pancreatitis

    PubMed Central

    Patel, Krutika; Durgampudi, Chandra; Noel, Pawan; Trivedi, Ram N.; de Oliveira, Cristiane; Singh, Vijay P.

    2017-01-01

    Although ethanol causes acute pancreatitis (AP) and lipolytic fatty acid (FA) generation worsens AP, the contribution of ethanol metabolites of FAs, ie, FA ethyl esters (FAEEs), to AP outcomes is unclear. Previously, pancreata of dying alcoholics and pancreatic necrosis in severe AP, respectively, showed high FAEEs and FAs, with oleic acid (OA) and its ethyl esters being the most abundant. We thus compared the toxicities of FAEEs and their parent FAs in severe AP. Pancreatic acini and peripheral blood mononuclear cells were exposed to FAs or FAEEs in vitro. The triglyceride of OA (i.e., glyceryl tri-oleate) or OAEE was injected into the pancreatic ducts of rats, and local and systemic severities were studied. Unsaturated FAs at equimolar concentrations to FAEEs induced a larger increase in cytosolic calcium, mitochondrial depolarization, and necro-apoptotic cell death. Glyceryl tri-oleate but not OAEE resulted in 70% mortality with increased serum OA, a severe inflammatory response, worse pancreatic necrosis, and multisystem organ failure. Our data show that FAs are more likely to worsen AP than FAEEs. Our observations correlate well with the high pancreatic FAEE concentrations in alcoholics without pancreatitis and high FA concentrations in pancreatic necrosis. Thus, conversion of FAs to FAEE may ameliorate AP in alcoholics. PMID:26878214

  13. Graphene as a photothermal actuator for control of lipid mesophase structure.

    PubMed

    Quinn, Matthew D J; Wang, Tao; Du, Joanne D; Boyd, Ben J; Hawley, Adrian; Notley, Shannon M

    2017-01-07

    The optical density of pristine graphene is high and broad in the near infrared region of the electromagnetic spectrum positioning this material as a highly efficient photothermal agent for in vivo applications. In this study, surfactant assisted exfoliated graphene was incorporated within bulk lipid samples of varying lipid types: glyceryl monoether, glyceryl monooleate and phytantriol. The pristine graphene sheets did not disrupt the packing of the liquid crystals while being in sufficiently intimate contact to provide localized heating and induce phase transitions. The phase progressions induced through heating using NIR irradiation of the entrained graphene particles within the bulk liquid crystal were studied using SAXS and confirmed using polarized optical microscopy. Increases in apparent temperature experienced by the matrix of up to 50 °C were observed by establishing a SAXS versus bulk temperature calibration curve allowing in situ measurements. The studies demonstrate the potential for use of graphene as a photothermal actuator across a range of lipid based systems of interest in controlled drug delivery.

  14. Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films.

    PubMed

    Ammar, Hussein O; Ghorab, Mamdouh M; Felton, Linda A; Gad, Shadeed; Fouly, Aya A

    2016-06-01

    Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.

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

    PubMed

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

    2014-01-01

    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.

  16. Microfluidic chip containing porous gradient for chemotaxis study

    NASA Astrophysics Data System (ADS)

    Al-Abboodi, Aswan; Tjeung, Ricky; Doran, Pauline; Yeo, Leslie; Friend, James; Chan, Peggy

    2011-12-01

    We have developed a new porous gradient microfluidic device based on in situ Gtn-HPA/CMC-Tyr hydrogel that comprises gelatin hydroxyphenylpropionic acid (Gtn-HPA) conjugate and carboxymethyl cellulose tyramine (CMC-Tyr) conjugate. The device is fabricated using a soft lithographic technique, in which microstructures were patterned on a thin layer of polydimethylsiloxane (PDMS) using a polymeric mold. Human fibrosarcoma cells (HT1080) were employed as invasive cancer cell model. Porosity gradients were generated by flowing pore etching fluid in the gradient generator network. Results suggested that spatial control of the porosity can be obtained, which mimics the 3-dimensional microenvironment in vivo for cell-based screening applications including real time chemotaxis, cytotoxicity, and continuous drug-response monitoring. A chemoattractant gradient is then generated and cell migration is monitored in real time using fluorescence microscopy. The viability of cells was evaluated using calcien AM stain. Herein, we successfully monitored the chemotactic responses of cancer cells, confirmed the validity of using in situ porous hydrogels as a construction material for a microchemotaxis device, and demonstrated the potential of the hydrogel with tunable porosity based microfluidic device in biological experiments. This device will also be practical in controlling the chemical and mechanical properties of the surroundings during the formation of tissue engineered constructs.

  17. Micromechanical and macroscopic models of ductile fracture in particle reinforced metallic materials

    NASA Astrophysics Data System (ADS)

    Hu, Chao; Bai, Jie; Ghosh, Somnath

    2007-06-01

    This paper is aimed at developing two modules contributing to the overall framework of multi-scale modelling of ductile fracture of particle reinforced metallic materials. The first module is for detailed micromechanical analysis of particle fragmentation and matrix cracking of heterogeneous microstructures. The Voronoi cell FEM for particle fragmentation is extended in this paper to incorporate ductile failure through matrix cracking in the form of void growth and coalescence using a non-local Gurson-Tvergaard-Needleman (GTN) model. In the resulting enriched Voronoi cell finite element model (VCFEM) or E-VCFEM, the assumed stress-based hybrid VCFEM formulation is overlaid with narrow bands of displacement based elements to accommodate strain softening in the constitutive behaviour. The second module develops an anisotropic plasticity-damage model in the form of the GTN model for macroscopic analysis in the multi-scale material model. Parameters in this model are calibrated from results of homogenization of microstructural variables obtained by E-VCFEM analysis of microstructural representative volume element. Numerical examples conducted yield satisfactory results.

  18. Organic nitrates and nitrate tolerance--state of the art and future developments.

    PubMed

    Daiber, Andreas; Münzel, Thomas; Gori, Tommaso

    2010-01-01

    The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two "traditional" hypotheses of nitrate tolerance, that is, the one postulating a decreased bioactivation and the concurrent one suggesting a role of oxidative stress. Furthermore, recent animal and human experimental studies suggest that the organic nitrates are not a homogeneous group but demonstrate a broad diversity with regard to induction of vascular dysfunction, oxidative stress, and other side effects. In the past, attempts to avoid nitrate-induced side effects have focused on administration schedules that would allow a "nitrate-free interval"; in the future, the role of co-therapies with antioxidant compounds and of activation of endogeneous protective pathways such as the heme oxygenase 1 (HO-1) will need to be explored. However, the development of new nitrates, for example, tolerance-free aminoalkyl nitrates or combination of nitrate groups with established cardiovascular drugs like ACE inhibitors or AT(1)-receptor blockers (hybrid molecules) may be of great clinical interest.

  19. Clinical Usefulness of Immunohistochemical Staining of p57kip2 for the Differential Diagnosis of Complete Mole

    PubMed Central

    Sasaki, Shigeru; Sasaki, Yasushi; Kunimura, Toshiaki; Sekizawa, Akihiko; Kojima, Yoshihiro; Iino, Koichi

    2015-01-01

    Objective. Can polymer-based immunohistochemical staining of p57kip2 replace DNA analysis as an inexpensive means of differentiating complete mole from partial mole or hydropic abortion? Methods and Materials. Original paraffin-embedded tissue blocks from 14 equivocal cases were turned over to our laboratory and examined by immunohistochemical staining of p57kip2. Results. Four of the 14 cases showed clearly negative nuclear staining in cytotrophoblasts and villous stromal cells: these results were fully concordant with the control staining. The remaining 10 cases showed apparently positive staining in cytotrophoblasts and villous stromal cells. Without DNA analysis we are able to clearly differentiate the 4 cases of complete mole among the 14 equivocal cases. During follow-up, secondary low-risk gestational trophoblastic neoplasia (GTN) developed in 1 of the 4 cases of complete mole: the GTN was treated by single-agent chemotherapy. No subsequent changes were observed during follow-up in the other cases. Conclusion. Polymer-based immunohistochemical staining of p57kip2 (paternally imprinted gene, expressed from maternal allele) is a very effective method that can be used to differentiate androgenetic complete mole from partial mole and hydropic abortion. We might be able to avoid the cost of DNA analysis. PMID:26161420

  20. Enzymatic remediated biodegradation of propylene glycol 1,2-dinitrate

    SciTech Connect

    Meng, M.; Geelhaar, L.; Speedie, M.K.

    1995-12-31

    Two bacterial species, Enterobacter agglomerans and Bacillus thuringiensis/cereus, which were selected from nitroglycerin (GTN) contaminated soil, have previously been shown to have denitrating ability on nitroglycerin. This abstract presents the investigation of the cell free extracts from both microorganisms for the degradation of another nitrate ester contaminant; propylene glycol 1,2-dinitrate (PGDN). This compound has been previously considered resistant to the biodegradation. In order to probe the pathway, the whole process was monitored by using [1-{sup 14}C]-PGDN as substrate and the intermediates were identified by HPLC and TLC chromatography. Long term biodegradation experiments have shown that the enzymes in the cytoplasm fraction of Bacillus thuringiensis/cereus and the membrane fraction of Enterobacter agglomerans convert PGDN successively into propylene glycol 1-mononitrate (1-PGMN) and propylene glycol 2-mononitrate (2-PGMN), and finally, propylene glycol. The capacity to achieve sequential and complete degradation of PGDN implies that it follows a similar mechanism to that observed in the GTN degradation. Cofactor requirements for PGDN breakdown have been studied, it was found that no dissociable, dialyzable cofactors are required.

  1. Alternative 5' untranslated regions are involved in expression regulation of human heme oxygenase-1.

    PubMed

    Kramer, Marcel; Sponholz, Christoph; Slaba, Monique; Wissuwa, Bianka; Claus, Ralf A; Menzel, Uwe; Huse, Klaus; Platzer, Matthias; Bauer, Michael

    2013-01-01

    The single nucleotide polymorphism rs2071746 and a (GT)n microsatellite within the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or outcome in a variety of diseases. Most of these associations involve either release of heme or oxidative stress. Both polymorphisms are localized in the promoter region, but previously reported correlations with heme oxygenase-1 expression remain not coherent. This ambiguity suggests a more complex organization of the 5' gene region which we sought to investigate more fully. We evaluated the 5' end of HMOX1 and found a novel first exon 1a placing the two previously reported polymorphisms in intronic or exonic positions within the 5' untranslated region respectively. Expression of exon 1a can be induced in HepG2 hepatoma cells by hemin and is a repressor of heme oxygenase-1 translation as shown by luciferase reporter assays. Moreover, minigene approaches revealed that the quantitative outcome of alternative splicing within the 5' untranslated region is affected by the (GT)n microsatellite. This data supporting an extended HMOX1 gene model and provide further insights into expression regulation of heme oxygenase-1. Alternative splicing within the HMOX1 5' untranslated region contributes to translational regulation and is a mechanistic feature involved in the interplay between genetic variations, heme oxygenase-1 expression and disease outcome.

  2. High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review

    PubMed Central

    Yamamoto, Eiko; Niimi, Kaoru; Fujikake, Kayo; Nishida, Tetsuya; Murata, Makoto; Mitsuma, Ayako; Ando, Yuichi; Kikkawa, Fumitaka

    2016-01-01

    Choriocarcinoma is a malignant gestational trophoblastic neoplasia (GTN) and one of the curable types of gynecological cancer. However, 10% of choriocarcinoma patients have a poor prognosis, particularly when they have metastasis, apart from pulmonary metastasis, or do not go into remission by the second chemotherapeutic regimen. We herein present the case of a 36-year-old patient who had choriocarcinoma with metastases to the lungs, liver and kidneys. The 5th and 6th regimens with cisplatin for choriocarcinoma failed and the patient developed brain metastases. She was then treated with four cycles of high-dose ifosfamide, carboplatin and etoposide (ICE) with blood progenitor cell support after confirming the effectiveness of ICE at normal doses. The serum human chorionic gonadotropin (hCG) level was 140,009 mIU/ml at the start of high-dose ICE and the patient tolerated this regimen well. However, the beneficial effect was decreasing with each successive course of treatment, with the lowest level of hCG at 103 mIU/ml after the fourth course. The patient did not achieve complete remission and succumbed to the disease 4 months after the last chemotherapy. The findings of the present case and a review of the related literature suggest that high-dose ICE with stem cell rescue may be considered as a viable treatment option for a multi-drug resistant choriocarcinoma or GTN. PMID:27900108

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

    PubMed

    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

    2015-01-01

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    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

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

    PubMed Central

    Chen, Ying-Chen; Liu, Der-Zen; Liu, Jun-Jen; Chang, Tsung-Wei; Ho, Hsiu-O; Sheu, Ming-Thau

    2012-01-01

    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® Once™ (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® Once™, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™. PMID:22923986

  6. Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample.

    PubMed

    Brochado, Maria José Franco; Gatti, Maria Fernanda Chociay; Zago, Marco Antônio; Roselino, Ana Maria

    2016-02-01

    Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

  7. HDR quality assurance methods for personal digital assistants.

    PubMed

    Astrahan, Melvin A

    2004-01-01

    An important component of every clinical high-dose-rate (HDR) brachytherapy program is quality assurance (QA). One of the QA recommendations of the AAPM TG59 report is an independent verification on the results of treatment planning. It is desirable for the verification procedure to be as quick and easy to perform as possible and yet to have a high probability of detecting significant errors. The objective of this work is to describe the dosimetric methods and software developed to implement a departmental HDR QA program using personal digital assistants (PDAs). Verification of MammoSite treatment plans is presented as a practical example. PDAs that run the PalmOS were selected for their low cost and popularity among health care professionals. General-purpose applications were developed for linear sources, planar, and volume implants, that estimate the total dwell time of an HDR implant. This value can then be compared to the total dwell time calculated by the primary treatment planning system. The software incorporates the Paterson-Parker (PP) radium tables and the Greenfield-Tichman-Norman (GTN) version of the Quimby radium tables, which have been modified to a form more convenient for HDR calculations. A special purpose application based on the AAPM TG43 formalism was developed for the MammoSite breast applicator. For QA calculations perpendicular to the center of a single Iridium-192 (192I) HDR source, as exemplified by MammoSite treatments, linearly interpolating the PP or GTN tables is equivalent to applying the TG43 formalism at distances up to 5 cm from the source axis. The MammoSite-specific software also offers the option to calculate dosimetry based on the balloon volume. The PDA clock/calendar permits the software to automatically account for source decay. The touch-sensitive screen allows the familiar tabular format to be maintained while minimizing the effort required for calculations. The PP and GTN radium implant tables are easily modified to a form

  8. Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

    PubMed Central

    Brochado, Maria José Franco; Gatti, Maria Fernanda Chociay; Zago, Marco Antônio; Roselino, Ana Maria

    2016-01-01

    Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively. PMID:26814595

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

    PubMed

    Wavikar, Preeti R; Vavia, Pradeep R

    2015-01-01

    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.

  10. Biosynthesis of murein lipoprotein in Escherichia coli: effects of 3,4-dihydroxybutyl-1-phosphonate.

    PubMed Central

    Chattopadhyay, P K; Engel, R; Tropp, B E; Wu, H C

    1979-01-01

    The effects of 3,4-dihydroxybutyl-1-phosphonate, a four-carbon analog of sn-glycerol 3-phosphate, on the biosynthesis of the glyceryl moiety in murein lipoprotein of Escherichia coli were studied. The compound at a concentration of 55 microM strong inhibits in the incorporation of [2-3H]glycerol radioactivity into lipoprotein by virtue of its inhibition of the synthesis of phosphatidylglycerol. On the other hand, the incorporation of prelabeled [2-3H]glycerol radioactivity into lipoprotein was only partially inhbited by 3,4-dihydroxybutyl-1-phosphonate even at a much higher concentration (1 mM). These data were consistent with the postulated pathway for the biosynthesis of the lipid moiety in lipoportein: cysteine-lipoprotein + phosphatidylglycerol leads to glycerylcystein-lipoprotein + phosphatidic acid. PMID:378946

  11. Guaifenesin in rhinitis.

    PubMed

    Storms, William; Farrar, Judith R

    2009-03-01

    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.

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

    PubMed

    Chowdhury, Mehrin; Kataky, Ritu

    2016-01-04

    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.

  13. Effects of double-layer polarization on ion transport.

    PubMed Central

    Hainsworth, A H; Hladky, S B

    1987-01-01

    It has been proposed that changes in ionic strength will alter the shape of current-voltage relations for ion transport across a lipid membrane. To investigate this effect, we measured currents across glyceryl monooleate membranes at applied potentials between 10 and 300 mV using either gramicidin and 1 mM NaCl or valinomycin and 1 mM KCl. A bridge circuit with an integrator as null detector was used to separate the capacitative and ionic components of the current. The changes in the current-voltage relations when ionic strength is varied between 1 and 100 mM are compared with predictions of Gouy-Chapman theory for the effects of these variations on polarization of the electrical diffuse double-layer. Double-layer polarization accounts adequately for the changes observed using membranes made permeable by either gramicidin or valinomycin. PMID:2432953

  14. Mycobacteriocins produced by rapidly growing mycobacteria are Tween-hydrolyzing esterases.

    PubMed Central

    Saito, H; Tomioka, H; Watanabe, T; Yoneyama, T

    1983-01-01

    Smegmatocin, a protein produced by Mycobacterium smegmatis ATCC 14468, was found to have an esterase activity, hydrolyzing Tween 80, polyoxyethylene sorbitan monooleate, added to the assay medium for various "bacteriocins" from mycobacteria. Because M. diernhoferi ATCC 19340 (indicator strain for smegmatocin) is highly susceptible to oleic acid and smegmatocin requires Tween 80 for manifestation of its anti-M. diernhoferi activity, it is likely that smegmatocin-mediated antimicrobial action is caused by oleic acid generated by hydrolysis of Tween 80 by the inherent esterase action of smegmatocin. Other mycobacteriocins from rapidly growing mycobacteria also have inherent esterase activity against Tween 80 and require Tween 80 for expression of antimycobacterial action. Smegmatocin was found to hydrolyze various polyoxyethylene (sorbitan) fatty acyl esters but not sorbitan monooleate and glyceryl esters. Images PMID:6826523

  15. Effects of double-layer polarization on ion transport.

    PubMed

    Hainsworth, A H; Hladky, S B

    1987-01-01

    It has been proposed that changes in ionic strength will alter the shape of current-voltage relations for ion transport across a lipid membrane. To investigate this effect, we measured currents across glyceryl monooleate membranes at applied potentials between 10 and 300 mV using either gramicidin and 1 mM NaCl or valinomycin and 1 mM KCl. A bridge circuit with an integrator as null detector was used to separate the capacitative and ionic components of the current. The changes in the current-voltage relations when ionic strength is varied between 1 and 100 mM are compared with predictions of Gouy-Chapman theory for the effects of these variations on polarization of the electrical diffuse double-layer. Double-layer polarization accounts adequately for the changes observed using membranes made permeable by either gramicidin or valinomycin.

  16. High-Throughput Quantification of Bioactive Lipids by MALDI Mass Spectrometry: Application to Prostaglandins

    PubMed Central

    Manna, Joseph D.; Reyzer, Michelle L.; Latham, Joey C.; Weaver, C. David; Marnett, Lawrence J.; Caprioli, Richard M.

    2011-01-01

    Analysis and quantification of analytes in biological systems is a critical component of metabolomic investigations of cell function. The most widely used methods employ chromatographic separation followed by mass spectrometric analysis, which requires significant time for sample preparation and sequential chromatography. We introduce a novel high-throughput, separation-free methodology based on MALDI mass spectrometry that allows for the parallel analysis of targeted metabolomes. Proof-of-concept is demonstrated by analysis of prostaglandins and glyceryl prostaglandins. Derivatization to incorporate a charged moiety into ketone-containing prostaglandins dramatically increases the signal-to-noise ratio relative to underivatized samples. This resulted in an increased dynamic range (15 fmol – 2000 fmol on plate) and improved linearity (r2= 0.99). The method was adapted for high-throughput screening methods for enzymology and drug discovery. Application to cellular metabolomics was also demonstrated. PMID:21770391

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

    PubMed

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

    2015-12-30

    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.

  18. Assessment of Gasoline Additive Containing Ditert-butoxypropanol

    SciTech Connect

    West, Brian H.; Connatser, Raynella M.; Lewis, Samuel Arthur

    2016-04-01

    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.

  19. Comprehension of direct extraction of hydrophilic antioxidants using vegetable oils by polar paradox theory and small angle X-ray scattering analysis.

    PubMed

    Li, Ying; Fabiano-Tixier, Anne Sylvie; Ruiz, Karine; Rossignol Castera, Anne; Bauduin, Pierre; Diat, Olivier; Chemat, Farid

    2015-04-15

    Since the polar paradox theory rationalised the fact that polar antioxidants are more effective in nonpolar media, extractions of phenolic compounds in vegetable oils were inspired and achieved in this study for obtaining oils enriched in phenolic compounds. Moreover, the influence of surfactants on the extractability of phenolic compounds was experimentally studied first, followed by the small angle X-ray scattering analysis for the oil structural observation before and after extraction so as to better understand the dissolving mechanism underpinning the extraction. The results showed a significant difference on the extraction yield of phenolic compounds among oils, which was mainly dependent on their composition instead of the unsaturation of fatty acids. Appropriate surfactant additions could significantly improve extraction yield for refined sunflower oils, which 1% w/w addition of glyceryl oleate was determined as the optimal. Besides, 5% w/w addition of lecithin performed the best in oil enrichments compared with mono- and di-glycerides.

  20. Effects of ascorbic acid supplementation on male reproductive system during exposure to hypoxia

    NASA Astrophysics Data System (ADS)

    Havazhagan, G.; Riar, S. S.; Kain, A. K.; Bardhan, Jaya; Thomas, Pauline

    1989-09-01

    Two groups of male rats were exposed to simulated altitudes of 6060 m and 7576 m for 6 h/day for 7 days (intermittent exposure). In two additional groups of animals exposed to the same altitude, 100 mg of ascorbic acid (AA) was fed daily for 5 days prior to the exposure period and also during the exposure period. Rats that did not receive AA showed loss of body weight and weight of reproductive organs after exposure. Sex organs showed atrophy on histological examination and there was a deterioration in spermatozoal quality. There was an increase in alkaline and acid phosphatase, and decrease in protein, sialic acid and glyceryl phosphorylcholine content in various reproductive tissues after exposure. All the above changes in histology and biochemical composition could be partially prevented by AA supplementation. AA supplementation can therefore protect the male reproductive system from deleterious effects of hypoxia. The probable mechanism of action of AA is discussed.

  1. Agents that activate protein kinase C reduce acetylcholine sensitivity in cultured myotubes

    PubMed Central

    1985-01-01

    We have examined acetylcholine (ACh)-elicited potentials or currents in current- or voltage-clamped cultured myotubes exposed to 12-O- tetradecanoyl-phorbol-13-acetate (TPA), a potent tumor promoter that activates protein kinase C. Although this agent had little action on either membrane resting potential or electrical resistance, a reversible decrease in ACh sensitivity was induced on 3-4-d-old chick myotubes. Depression of transmitter action by TPA was extended to 7-8-d mouse myotubes only when they were treated with phosphatidylserine. Glyceryl dioleate had effects on myotubes similar to those of TPA but with a reduced efficacy. We conclude that the activation of protein kinase C might be involved with the capacity of ACh receptors to respond to transmitter stimulation. PMID:3156868

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

    PubMed

    Schulz, S

    2001-06-01

    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.

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

    PubMed

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

    2016-06-10

    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.

  4. Spheronization of solid lipid extrudates: A novel approach on controlling critical process parameters.

    PubMed

    Petrovick, Gustavo Freire; Pein, Miriam; Thommes, Markus; Breitkreutz, Jörg

    2015-05-01

    Solid lipids are non-toxic excipients, which are known to potentially enhance delivery and bioavailability of poorly water-soluble drugs and moreover to mask unpleasant tasting drugs. Multiple unit matrix dosage forms based on solid lipids, such as lipid pellets, can be obtained by solvent-free cold extrusion and spheronization. This method presents advantages in the processing of sensitive substances, such as low process temperatures, the absence of solvents and a drying step. However, the material temperature during the spheronization showed to be critical so far. The process leads to increased material temperatures, causing particle agglomeration and discontinuity of the spheronization. In the present study, extrudates of 0.5mm in diameter containing metformin hydrochloride, and either semisynthetic hard fat (Witocan® 42/44) or different ternary mixtures based on hard fat, glyceryl trimyristate, and glyceryl distearate, were spheronized. By applying common process parameters, particle agglomeration or material stickiness on equipment walls was observed in preliminary experiments after 2-6min, depending on the lipid composition. Therefore, an innovative instrumental setup to control the spheronization process was developed utilizing an infrared light source, which was positioned over the particle bed. The new approach enabled a spheronization process that reached the desired spheronization temperature after 2-3min and neither particle agglomeration nor material adherence occurred even after longer process times. The different formulations, even those based on high amount of solid lipids, were successfully spheronized over 15min, resulting in small diameter lipid pellets with smooth surface and aspect ratios below 1.3.

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

    PubMed Central

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

    2016-01-01

    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/cm2, 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. PMID:27222612

  6. Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol

    PubMed Central

    Li, Jian-Chun; Zhu, Na; Zhu, Jin-Xiu; Zhang, Wen-Jing; Zhang, Hong-Min; Wang, Qing-Qing; Wu, Xiao-Xiang; Wang, Xiu; Zhang, Jin; Hao, Ji-Fu

    2015-01-01

    Background The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. Material/Methods In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. Results Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. Conclusions The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application. PMID:26517086

  7. Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS).

    PubMed

    Setthacheewakul, Saipin; Kedjinda, Wichan; Maneenuan, Duangkhae; Wiwattanapatapee, Ruedeekorn

    2011-03-01

    The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9-32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.

  8. Effect of arvanil (N-arachidonoyl-vanillyl-amine), a nonpungent anandamide-capsaicin hybrid, on ion currents in NG108-15 neuronal cells.

    PubMed

    Lo, Yuk-Keung; Chiang, Hung-Ting; Wu, Sheng-Nan

    2003-02-15

    The effects of arvanil (N-arachidonoyl-vanillyl-amine), a structural hybrid between capsaicin and anandamide, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. Arvanil (0.2-50 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Arvanil produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of arvanil-induced inhibition of I(Ca,L) was 2 microM. Arvanil (5 microM) could shift the steady-state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. No effect of arvanil (20 microM) on delayed rectifier K(+) current (I(K(DR))) was observed; however, capsaicin (20 microM), glyceryl nonivamide (20 microM) and capsinolol (20 microM) suppressed it significantly. Arvanil (20 microM) caused a slight reduction in the amplitude of erg (ether-à-go-go-related)-mediated K(+) current (I(K(erg))) without modifying the activation curve of this current, while capsaicin and glyceryl nonivamide were more effective in suppressing I(K(erg)). Under current-clamp configuration, arvanil decreased the firing frequency of action potentials. Arvanil-mediated inhibition of I(Ca,L) appeared to be independent of its binding to either vanilloid or cannabinoid receptors. The channel-blocking properties of arvanil may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

  9. Quantitative microleakage of some dentinal bonding restorative systems.

    PubMed

    Hasegawa, T; Retief, D H

    1993-03-01

    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.

  10. Hearing Protection for High-Noise Environments. Atachment 1: Development of Elastoacoustic Integral-Equation Solver: Surface and Volumetric Integral Equations

    DTIC Science & Technology

    2009-11-30

    approach we developed, mostly in order to be able to efficiently model geometry components – in our case, the middle and inner ear – characterized by...such as 1. Modeling of man-made objects of possibly complex geometrical shapes, but consisting of only few homogeneous materials. 2. Solution of the...ΓTm(t, r ′) · u(r′) +GTm(r, r′) · t(r′) ] = δm0 u in(r) for r ∈ Smn , (2.1a) 1 2 u(r)− ∫ Smn d2r′ [ ΓTn (t, r ′) · u(r′) + GTn (r, r′) · t(r′) ] + ∑ S

  11. Damage and Failure Analysis of AZ31 Alloy Sheet in Warm Stamping Processes

    NASA Astrophysics Data System (ADS)

    Zhao, P. J.; Chen, Z. H.; Dong, C. F.

    2016-07-01

    In this study, a combined experimental-numerical investigation on the failure of AZ31 Mg alloy sheet in the warm stamping process was carried out based on modified GTN damage model which integrated Yld2000 anisotropic yield criterion. The constitutive equations of material were implemented into a VUMAT subroutine for solver ABAQUS/Explicit and applied to the formability analysis of mobile phone shell. The morphology near the crack area was observed using SEM, and the anisotropic damage evolution at various temperatures was simulated. The distributions of plastic strain, damage evolution, thickness, and fracture initiation obtained from FE simulation were analyzed. The corresponding forming limit diagrams were worked out, and the comparison with the experimental data showed a good agreement.

  12. A Comparative Study of Failure with Incremental Forming

    NASA Astrophysics Data System (ADS)

    Wu, S. H.; Song, N. N.; Pires, F. M. Andrade

    2016-08-01

    Incremental forming (ISF) is an innovative flexible sheet metal forming process which can be used to manufacture complex shapes from various materials. Due to its flexibility, it has attracted more and more attention over recent decades. Localized deformation and shear through the thickness are essential characteristics of ISF. These lead to specific failure modes and formability of ISF that are different from the conventional stamping process. In this contribution, three continuum damage models (Lemaitre, Gurson, extended GTN models) are formulated and fully coupled with the finite element simulation in a commercial software ABAQUS to predict failure in incremental forming. A comparative investigation of these three damage models has been carried out to analyze both the deformation behavior and failure mechanisms.

  13. Examination of the damage and failure response of tantalum and copper under varied shock loading conditions

    SciTech Connect

    Bronkhorst, Curt A; Dennis - Koller, Darcie; Cerreta, Ellen K; Gray Ill, George T; Bourne, Neil

    2010-12-16

    A number of plate impact experiments have been conducted on high purity polycrystalline tantalum and copper samples using graded flyer plate configurations to alter the loading profile. These experiments are designed in a way so that a broad range of damage regimes are probed. The results show that the nucleation of damage primarily occurs at the grain boundaries of the materials. This affords us the opportunity to propose a porosity damage nucleation criterion which begins to account for the length scales of the microstructure (grain size distribution) and the mechanical response of the grain boundary regions (failure stress distribution). This is done in the context of a G-T-N type model for the ductile damage and failure response of both the materials examined. The role of micro-inertial effects on the porosity growth process is also considered.

  14. Characterisation of steel components under monotonic loading by means of image-based methods

    NASA Astrophysics Data System (ADS)

    Xavier, J.; Pereira, J. C. R.; de Jesus, A. M. P.

    2014-02-01

    Ductile damage behaviour of S185 structural steel is determined by coupling numerical and experimental analyses. Monotonic experimental tests are carried out in five different specimen configurations. These mechanical tests are coupled with image-based methods for assessing displacement and strain fields over the gauge section. Three different ductile damage models proposed in the literature for monotonic loading are analysed. Their governing parameters are determined by comparing experimental and numerical mechanical responses. Measurements provided by digital image correlation and feature-tracking methods are used for calibrating and validating non-linear finite element modelling. Numerical analyses built in ANSYS are carried out to compute the necessary parameters (stress-strain and triaxiality histories) to calibrate Johnson-Cook (JC) and Kanvinde-Deierlein (KD) fracture criteria. Also, a calibration of the Gurson-Tvergaard-Needleman (GTN) model is performed based on an explicit finite element analysis in ABAQUS.

  15. Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter

    PubMed Central

    Zhang, Jia-Qiang; Zhang, Jian-Qing; Fang, Li-Zhou; Liu, Ling; Fu, Wei-Ping; Dai, Lu-Ming

    2015-01-01

    Background Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients. N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients. We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC. Methods A total of 368 patients with COPD were recruited and the polymorphisms of their HO-1 gene promoter were classified into three subclasses according to the number of (GT)n repeats, as previously reported: class S (<27 (GT)n repeats), class M (27–32 (GT)n repeats), and class L (>32 (GT)n repeats). These subjects were then classified as L+ group (with the L allele: L/L, L/M, L/S) and L− group (without the L allele: M/M, M/S, S/S). All the patients were allocated to standard therapy plus NAC 600 mg bid over a 1-year period and were observed over that year. Results The L− group saw improvements in forced expiratory volume in 1 second (FEV1) (from 1.44±0.37 to 1.58±0.38, P=0.04) and FEV1% predicted (from 56.6±19.2 to 59.7±17.2, P=0.03). No improvement was found in forced vital capacity of each group and the decline of forced vital capacity in both of the groups was not statistical significant. The number of yearly COPD exacerbations of the L− group was 1.5±0.66 which was lower than the 2.1±0.53 of the L+ group (P<0.01). For the changes of St George’s Respiratory Questionnaire (SGRQ) score, only the activity score of the L− group was more significant than that of the L+ group (P=0.02). The improvement of the outcome of 6-minute walking distance test in L− group (from 290.1±44.9 meters to 309.7±46.9 m) was higher than that in the L+ group (from 289.7±46.2 m to 300.3±44.2 m) (P=0.03). Conclusion A 600 mg bid oral NAC treatment for 1-year on COPD patients without the L allele can improve the FEV1, FEV1% predicted, the SGRQ activity score, and

  16. The influence of the molecular system on the performance of heteronuclear decoupling in solid-state NMR

    NASA Astrophysics Data System (ADS)

    Gerbaud, Guillaume; Caldarelli, Stefano; Ziarelli, Fabio; Gastaldi, Stéphane

    2011-05-01

    The intensity of the carbon signal in a CPMAS experiment has been measured for two CH and three CH 2 moieties in four test molecules under different phase-modulated proton decoupling conditions and as a function of the spinning rate. The proton decoupling schemes investigated were the golden standard TPPM and three of the GTn family. Aim of this analysis was to better describe experimentally the impact and limitations of phase-modulated decoupling. Sizeable differences in the response to decoupling were observed in otherwise chemically identical molecular fragments, such as the CHCH 2 found in tyrosine, phenyl-succinic acid or 9-Anthrylmethyl-malonate, probably due to differences in spin-diffusion rates. In keeping with known facts, the efficiency of the decoupling was observed to decrease with the MAS rate, but with somewhat different trends for the tested systems.

  17. A Periosteum-Inspired 3D Hydrogel-Bioceramic Composite for Enhanced Bone Regeneration .

    PubMed

    Chun, Yong Yao; Wang, Jun Kit; Tan, Nguan Soon; Chan, Peggy Puk Yik; Tan, Timothy Thatt Yang; Choong, Cleo

    2016-02-01

    A 3D injectable hydrogel-bioceramic composite consisting of gelatin-3-(4-hydroxyphenyl) propionic acid (Gtn-HPA) and carboxymethyl cellulose-tyramine (CMC-Tyr), incorporated with fish scale-derived calcium phosphate (CaP), is developed for bone applications. The hydrogel-bioceramic composite has significantly improved the elastic modulus compared to the non-filled hydrogel, of which the addition of 10 w/v% CaP showed zero order fluorescein isothiocyanate (FITC)-dextran release profile and a significantly higher proliferation rate of encapsulated cells. All the samples promote the nucleation and growth of CaP minerals when exposed to 1× SBF. Overall, the hydrogel-bioceramic composite with 10 w/v% CaP can potentially be used as a periosteum-mimicking membrane to facilitate bone regeneration.

  18. Rare Presentation of Chorioadenoma Destruens as Acute Haemoperitoneum Mimicking Ruptured Ectopic Pregnancy.

    PubMed

    Sinha, M; Kaur, R; Gupta, R; Rani, R; Aggarwal, A

    2014-01-01

    Gestational trophoblastic neoplasms (GTN) are proliferative degenerative disorders of placental elements and include complete or partial mole (90%), invasivemole (5-8%), choriocarcinoma (1-2%) and placental site tumor (1-2%). Chorioadenoma destruens is a trophoblastic tumor, characterized by myometrial invasion through direct extension or via venous channels. We present a case of invasive mole eroding uterus and uterine vasculature, causing sudden rupture of uterus with massive haemoperitoneum mimicking ectopic pregnancy. A 20 year old G1P0 at 6 weeks gestation presented in Casualty of Kasturba Hospital complaining of severe acute onset lower abdominal pain for one hour. Clinical examination revealed shock. Sonography suggested ectopic pregnancy and immediate exploratory laparotomy was decided. On laparotomy, 2000cc of haemoperitoneum was noted. Grape like vesicles protruding through fundal perforation with profuse active bleeding was seen. Bleeding persisted despite evacuation. Step wise uterine devascularisation failed to achieve haemostasis. Total abdominal hysterectomy was performed as a life saving measure.

  19. No evidence for association between SLC11A1 and visceral leishmaniasis in India

    PubMed Central

    2011-01-01

    Background SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. Methods Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). Results No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. Conclusions This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India. PMID:21599885

  20. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

    PubMed Central

    2015-01-01

    Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

  1. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

    PubMed

    Daiber, Andreas; Münzel, Thomas

    2015-10-10

    Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

  2. Effect of potassium channel blockade and alpha 2-adrenoceptor activation on the release of nitric oxide from non-adrenergic non-cholinergic nerves.

    PubMed

    De Man, J G; Boeckxstaens, G E; Herman, A G; Pelckmans, P A

    1994-05-01

    1. Using a superfusion bioassay cascade, we studied the effect of K+ channel blockers and alpha 2-adrenoceptor agents on the release of a transferable factor, previously characterized as nitric oxide (NO) or a nitric oxide-related substance (NO-R), in response to non-adrenergic non-cholinergic (NANC) nerve stimulation in the canine ileocolonic junction (ICJ). 2. The non-selective K+ channel blockers, 4-aminopyridine (4-AP, 50 microM) and tetraethylammonium (TEA, 1 mM) and the more selective blocker of Ca(2+)-activated K+ channels, charybdotoxin (Leiurus quinquestriatus venom (LQV), 0.4 microgram ml-1), significantly enhanced the release of NO-R induced by low frequency stimulation (2-4 Hz). In the presence of 4-AP and TEA, the release of NO-R was nearly abolished by tetrodotoxin (2 microM), and by L-NG-nitroarginine (L-NOARG, 0.1 mM). Relaxations induced by direct injection of exogenous NO (5-50 pmol) or nitroglycerin (GTN, 10-30 pmol) onto the rabbit aortic detector ring were not affected. 3. The alpha 2-adrenoceptor agonist, UK-14,304 (0.3 microM) inhibited the release of NO-R induced by low (2-4 Hz), but not that induced by high (16 Hz), frequency stimulation. This inhibitory effect was completely reversed by the alpha 2-adrenoceptor antagonist, yohimbine (0.3 microM). Neither UK-14,304 nor yohimbine affected the relaxations induced by exogenous NO (5 pmol) or GTN (10 pmol) on the aortic detector ring.3+

  3. Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system

    PubMed Central

    Kesavan, K.; Nath, G.; Pandit, JK.

    2010-01-01

    Background and the purpose of the study The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of mucoadhesive in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac and have good mucoadhesion with ocular mucus layers. The objective of this study was to formulate ophthalmic mucoadhesive system of gatifloxacin (GTN) and to evaluate its in vitro antibacterial potential against, Staphylococcus aureus and Escherichia coli. Methods : Mucoadhesive systems were prepared using gellan combined with sodium carboxymethylcellulose (NaCMC) or sodium alginate to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their gelation, and rheological behaviors, mucoadhesion force, in vitro drug release, and antibacterial activity. Results All formulations in non-physiological or physiological conditions showed pseudoplastic behaviors. Increase in the concentration of mucoadhesive agent enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin from the mucoadhesive system in simulated tear fluid (STF, pH of 7.4) was influenced significantly by the properties and concentration of gellan, sodium carboxymethyl cellulose and sodium alginate. Significant reduction in the total bacterial count was observed between drug solution (control) and mucoadhesive batches against both tested organisms. Major conclusion The developed mucoadhesive system is a viable alternative to conventional eye drops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug. PMID:22615622

  4. Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair.

    PubMed

    Han, Fengxuan; Yang, Xiaoling; Zhao, Jin; Zhao, Yunhui; Yuan, Xiaoyan

    2015-04-01

    A layered gelatin-chitosan hydrogel with graded composition was prepared via photocrosslinking to simulate the polysaccharide/collagen composition of the natural tissue and mimic the multi-layered gradient structure of the cartilage-bone interface tissue. Firstly, gelatin and carboxymethyl chitosan were reacted with glycidyl methacrylate (GMA) to obtain methacrylated gelatin (Gtn-GMA) and carboxymethyl chitosan (CS-GMA). Then, the mixed solutions of Gtn-GMA in different methacrylation degrees with CS-GMA were prepared to form the superficial, transitional and deep layers of the hydrogel, respectively under the irradiation of ultraviolet light, while polyhedral oligomeric silsesquioxane was introduced in the deep layer to improve the mechanical properties. Results suggested that the pore sizes of the superficial, transitional and deep layers of the layered hydrogel were 115 ± 30, 94 ± 34, 51 ± 12 μm, respectively and their porosities were all higher than 80 %. The compressive strengths of them were 165 ± 54, 565 ± 50 and 993 ± 108 kPa, respectively and the strain of the gradient hydrogel decreased along the thickness direction, similar to the natural tissue. The in vitro cytotoxicity results showed that the hydrogel had good cytocompatibility and the in vivo repair results of osteochondral defect demonstrated remarkable recovery by using the gradient gelatin-chitosan hydrogel, especially when the hydrogel loading transforming growth factor-β1. Therefore, it was suggested that the prepared layered gelatin-chitosan hydrogel in this study could be potentially used to promote cartilage-bone interface tissue repair.

  5. Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

    PubMed

    Lahey, S J; Steele, G; Rodrick, M L; Berkowitz, R; Goldstein, D P; Ross, D S; Ravikumar, T S; Wilson, R E; Byrn, R; Thomas, P

    1984-03-15

    The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.

  6. Sequence structure and intragenomic variability of ribosomal ITS2 in monozoic tapeworms of the genus Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish.

    PubMed

    Králová-Hromadová, Ivica; Bazsalovicsová, Eva; Oros, Mikuláš; Scholz, Tomáš

    2012-10-01

    The sequence structure of the ribosomal internal transcribed spacer 2 (ITS2) was determined for six species of Khawia (Cestoda: Caryophyllidea), parasites of cyprinid fish in the Holarctic Region. Homologous intragenomic ITS2 structure was found in Khawia armeniaca, Khawia baltica, and Khawia rossittensis; whereas divergent intragenomic ITS2 copies were detected in Chinese, Japanese, and Slovak isolates of Khawia sinensis and in Khawia japonensis, both parasitic in common carp, and in Khawia saurogobii, recently described from Chinese lizard gudgeon in China. Despite distinct morphological differences between K. saurogobii and K. sinensis, both species display very high level of molecular homogeneity. Variation in number of short repetitive motifs [(GCCT)(n) (GCCC)(n)], [(GTG)(n)], [(ATAC)(n)], [ACGTGT (TCGTGT)(n)], [(GT)(n)], [(GT)(n)], and [(ACCT)(n) (GCCT)(n)] resulted in assortment of ITS2 sequences in four ITS2 variants in K. saurogobii from China, three in Chinese and Japanese isolates of K. sinensis, and five ITS2 variants in K. sinensis from Slovakia. In K. japonensis, the structure and arrangement of microsatellites was different from those of K. sinensis and K. saurogobii. The heterogeneity in the number of two microsatellite regions [(TG)(n); (TTG)(n)] divided ITS2 clones into two variants-first ITS2 variant (472 bp) with (TG)(5) and (TTG)(6), and second variant with (TG)(7) and (TTG)(2) (465 bp). Sequence identity of K. saurogobii with all but one (K. sinensis) congeneric species ranged between 49.5 and 69.2%, which corresponds to the interspecific differences. In contrast, sequence identity of K. saurogobii and K. sinensis (87.6-95.0%) failed into the range of intraspecific variation determined for K. sinensis samples. This close genetic similarity indicates that recently described K. saurogobii may have undergone morphological divergence as a result of ongoing sympatric speciation by host switching.

  7. Homogenization-based continuum plasticity-damage model for ductile failure of materials containing heterogeneities

    NASA Astrophysics Data System (ADS)

    Ghosh, Somnath; Bai, Jie; Paquet, Daniel

    2009-07-01

    This paper develops an accurate and computationally efficient homogenization-based continuum plasticity-damage (HCPD) model for macroscopic analysis of ductile failure in porous ductile materials containing brittle inclusions. Example of these materials are cast alloys such as aluminum and metal matrix composites. The overall framework of the HCPD model follows the structure of the anisotropic Gurson-Tvergaard-Needleman (GTN) type elasto-plasticity model for porous ductile materials. The HCPD model is assumed to be orthotropic in an evolving material principal coordinate system throughout the deformation history. The GTN model parameters are calibrated from homogenization of evolving variables in representative volume elements (RVE) of the microstructure containing inclusions and voids. Micromechanical analyses for this purpose are conducted by the locally enriched Voronoi cell finite element model (LE-VCFEM) [Hu, C., Ghosh, S., 2008. Locally enhanced Voronoi cell finite element model (LE-VCFEM) for simulating evolving fracture in ductile microstructures containing inclusions. Int. J. Numer. Methods Eng. 76(12), 1955-1992]. The model also introduces a novel void nucleation criterion from micromechanical damage evolution due to combined inclusion and matrix cracking. The paper discusses methods for estimating RVE length scales in microstructures with non-uniform dispersions, as well as macroscopic characteristic length scales for non-local constitutive models. Comparison of results from the anisotropic HCPD model with homogenized micromechanics shows excellent agreement. The HCPD model has a huge efficiency advantage over micromechanics models. Hence, it is a very effective tool in predicting macroscopic damage in structures with direct reference to microstructural composition.

  8. A profile of cases of gestational trophoblastic neoplasia at a large tertiary centre in dubai.

    PubMed

    Rangwala, Tasneem H; Badawi, Faiza

    2011-01-01

    Objectives. To study (1) the prevalence of different types of gestational trophoblastic neoplasia (GTN) in the local and nonlocal population of women at Al Wasl Hospital, a tertiary level referral centre for northern Emirates, (2) the safety of cervical preparation before uterine evacuation, (3) the role of repeat uterine evacuation in curing these cases, and (4) the percentage of cases ultimately requiring chemotherapy. Material and Methods. Retrospective analysis of case records of 35 women with diagnosis of gestational trophoblastic neoplasia were managed in the Department of Obstetrics and Gynecology at Al Wasl Hospital, over a 2-year period between January 2007 to December 2008. Results. 35 cases of gestational trophoblastic neoplasia were seen in a 2-year period (January 2007 to December 2008) at Al Wasl Hospital, with 7000 deliveries per year, prevalence being 1 in 400 live births. 60% cases were local Arabs. Histopathology revealed complete mole in 13 cases, partial mole in 17 cases, hydropic degeneration of villi in 4 cases, and no identifiable tissue in 1 case. No cases of choriocarcinoma or placental site trophoblastic tumour were seen during the study period. 34% cases received cervical preparation with prostaglandins prior to surgical curettage. Complications were minor. 62% were cured by primary suction curettage, 12% after second (repeat) uterine evacuation, and 25% needed single drug chemotherapy. 8% cases defaulted after primary evacuation and were lost to followup. Conclusions. Prevalence of GTN in the local Arab population is similar to other Asian populations. The majority of cases are cured by simple suction uterine curettage. Cervical preparation with prostaglandins should be done in selected cases to avoid perforation during evacuation. Second (repeat) uterine evacuation can be curative in some cases with strict selection criteria and avoid the need for chemotherapy. Regional registry of cases is needed to estimate the true incidence of this

  9. First-line chemotherapy in low-risk gestational trophoblastic neoplasia

    PubMed Central

    Alazzam, Mo’iad; Tidy, John; Hancock, Barry W; Osborne, Raymond; Lawrie, Theresa A

    2014-01-01

    Background This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. Objectives To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. Search methods In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review. Selection criteria For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials. Main results We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women). Overall, dactinomycin was associated

  10. Le nitrate double NaRb2(NO3)3, composé intermédiaire du système binaire isobare NaNO3 + RbNO3: études thermiques et cristallographiques

    PubMed Central

    Ksiksi, Nesrine; Driss, Mohamed; Hellali, Dalila; Guesmi, Abderrahmen; Zamali, Hmida

    2015-01-01

    Crystallographic and thermodynamic investigations of the binary (NaNO3 + RbNO3) phase diagram at atmospheric pressure reveal the existence of an inter­mediate compound NaRb2(NO3)3 (sodium dirubidium trinitrate) previously predicted and now reported experimentally for the first time. According to a DSC analysis, the compound exhibits three allotropic forms. In its low-temperature allotropic form (α form, ortho­rhom­bic) there are two Rb (m.. site symmetry) and one Na (m..) independent crystallographic positions and three planar nitrate groups. The bond-valence-sum calculations for all atoms agree well with their oxidation states. The Rb cations are located in the (100) plane at x = ½ with 11 oxygen coordination. The Na ones are in the same plane at x = 0 and are coordinated to eight O atoms from six nitrate groups. The charge-distribution method has been used to evaluate the degree of distortion of the alkali polyhedra. PMID:25995854

  11. Le nitrate double NaRb2(NO3)3, composé intermédiaire du système binaire isobare NaNO3 + RbNO3: études thermiques et cristallographiques.

    PubMed

    Ksiksi, Nesrine; Driss, Mohamed; Hellali, Dalila; Guesmi, Abderrahmen; Zamali, Hmida

    2015-05-01

    Crystallographic and thermodynamic investigations of the binary (NaNO3 + RbNO3) phase diagram at atmospheric pressure reveal the existence of an inter-mediate compound NaRb2(NO3)3 (sodium dirubidium trinitrate) previously predicted and now reported experimentally for the first time. According to a DSC analysis, the compound exhibits three allotropic forms. In its low-temperature allotropic form (α form, ortho-rhom-bic) there are two Rb (m.. site symmetry) and one Na (m..) independent crystallographic positions and three planar nitrate groups. The bond-valence-sum calculations for all atoms agree well with their oxidation states. The Rb cations are located in the (100) plane at x = ½ with 11 oxygen coordination. The Na ones are in the same plane at x = 0 and are coordinated to eight O atoms from six nitrate groups. The charge-distribution method has been used to evaluate the degree of distortion of the alkali polyhedra.

  12. Explosive double salts and preparation

    DOEpatents

    Cady, Howard H.; Lee, Kien-yin

    1984-01-01

    Applicants have discovered a new composition of matter which is an explosive addition compound of ammonium nitrate (AN) and diethylenetriamine trinitrate (DETN) in a 50:50 molar ratio. The compound is stable over extended periods of time only at temperatures higher than 46.degree. C., decomposing to a fine-grained eutectic mixture (which is also believed to be new) of AN and DETN at temperatures lower than 46.degree. C. The compound of the invention has an x-ray density of 1.61 g/cm.sup.3, explodes to form essentially only gaseous products, has higher detonation properties (i.e., detonation velocity and pressure) than those of any mechanical mixture having the same density and composition as the compound of the invention, is a quite insensitive explosive material, can be cast at temperatures attainable by high pressure steam, and is prepared from inexpensive ingredients. Methods of preparing the compound of the invention and the fine-grained eutectic composition of the invention are given.

  13. Design and Construction of a Non-Natural Malate to 1,2,4-Butanetriol Pathway Creates Possibility to Produce 1,2,4-Butanetriol from Glucose

    PubMed Central

    Li, Xinghua; Cai, Zhen; Li, Yin; Zhang, Yanping

    2014-01-01

    1,2,4-butanetriol (BT) is an important bulk chemical mainly used for producing the superior energetic plasticizer (1,2,4-butanetriol trinitrate) in propellant and explosive formulations. BT is commercially produced by chemical synthesis from petroleum-based feedstocks; until recently a costly biosynthetic route from xylose or arabinose was reported. Here we designed a novel biosynthetic pathway for BT from malate, for the purpose of using glucose as an alternative and cheaper substrate in future. This biosynthetic pathway was achieved through six sequential enzymatic reactions. Following tests of several combinations of enzymes for the pathway, five enzymes including malate thiokinase, succinate-semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, 4-hydroxybutyrate CoA-transferase and bifunctional aldehyde/alcohol dehydrogenase were finally chosen. All enzyme genes were expressed on two compatible plasmids in E. coli, and their functions verified separately. Following assembly of two functional modules, BT was detected in the fermentation broth upon addition of malate, proving BT can be biosynthesized from malate. Furthermore, BT was detected in the fermentation using glucose as the sole carbon source, suggesting that such novel BT biosynthetic pathway has created the possibility for the production of BT from the cheaper substrate glucose. PMID:25008973

  14. Analysis of Explosives by GC-UV.

    PubMed

    Andrasko, Jan; Lagesson-Andrasko, Ludmila; Dahlén, Johan; Jonsson, Bengt-Harald

    2017-01-10

    A mixture of explosives was analyzed by gas chromatography (GC) linked to ultraviolet (UV) spectrophotometry that enabled detection in the range of 178-330 nm. The gas-phase UV spectra of 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), ethylene glycol dinitrate (EGDN), glycerine trinitrate (NG, nitroglycerine), triacetone triperoxide (TATP), and pentaerythritol tetranitrate (PETN) were successfully recorded. The most interesting aspect of the current application is that it enabled simultaneous detection of both the target analyte and its decomposition products. At suitable elevated temperatures of the transfer line between the GC instrument and the UV detector, a partial decomposition was accomplished. Detection was made in real time and resulted in overlaid spectra of the mother compound and its decomposition product. Hence, the presented approach added another level to the qualitative identification of the explosives in comparison with traditional methods that relies only on the detection of the target analyte. As expected, the decomposition product of EGDN, NG, and PETN was NO, while TATP degraded to acetone. DNT and TNT did not exhibit any decomposition at the temperatures used.

  15. RX-08-HD, a low-viscosity, injection-moldable explosive for filling tortuous paths

    SciTech Connect

    Hoffman, D.M.; Jessop, E.S.; Swansiger, R.W.

    1997-10-01

    Cast cure, extrusion cast, and paste extrudable explosives have not been designed for transferring through long tortuous paths or into fine three dimensional shapes. To allow the crystalline explosive to flow a lubricating fluid is required. The energetic liquid ethane trinitrate (TMETN) was used as the lubricant to maximize the explosive energy. TMETN is a liquid nitrate ester which requires stabilization with conventional free radical stabilizers such as 2- nitrodiphenylamine, methyl-nitroanaline, or ethyl centrylite. Since these injection moldable explosives are expected to cure in place, a polyesterurethane binder based on polymeric isocyanate of hexamethylene diisocyanate and polycaprolactone polyols is dissolved in TMETN. The solubility of the polymer precursors in TMETN also reduces the energetic liquids sensitivity. The latent cure catalyst Dabco T-131 was used to minimize shrinkage associated with thermal expansion, reduce cost associated with oven cures, to give 4-6 hour potlife and overnight cure to handling strength. The product RX-08-HD is a new, low-viscosity, injection moldable explosive that can be extruded into complex, void-free shapes. Combined with appropriate design and other aspects of weaponization, RX-08-HD has produced outstanding results.

  16. Spontaneous trigeminal allodynia in rats: a model of primary headache.

    PubMed

    Oshinsky, Michael L; Sanghvi, Menka M; Maxwell, Christina R; Gonzalez, Dorian; Spangenberg, Rebecca J; Cooper, Marnie; Silberstein, Stephen D

    2012-10-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

  17. An oral yohimbine/l-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects

    PubMed Central

    Kernohan, A F B; McIntyre, M; Hughes, D M; Tam, S W; Worcel, M; Reid, J L

    2005-01-01

    Aims Interaction of phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction with organic nitrates could lead to severe hypotension. NMI 861 is a combination of 7.7 mg yohimbine tartrate and 6 g l-arginine glutamate. A similar oral combination, which contains the same amount of yohimbine and l-arginine, has been shown to improve erectile function in previous studies. Methods In two placebo-controlled, randomized, double-blind, two-way crossover design studies we aimed to assess first the pharmacokinetics and pharmacodynamics of a single oral dose of NMI 861 administered in 16 healthy male subjects, and then the pharmacodynamics of orally administered NMI 861 in combination with intravenous nitroglycerine (GTN) in 12 healthy male subjects. Systolic (SBP) and diastolic (DBP) blood pressures, pulse rate and adverse events were measured in each study. Results NMI 861 was well tolerated by all subjects with no significant adverse reactions reported. For l-arginine, mean Cmax ± SEM (range) was 42 ± 2.2 (28–63) µg ml−1 and tmax (range) was 0.88 (0.50–1.5) h. AUC and t1/2 were not calculated for l-arginine because of the presence of endogenous concentrations and the contribution from food sources. For yohimbine, mean Cmax was 42 ± 11 (2.8–128) ng ml−1; tmax was 0.57 (0.25–1.0) h; mean AUC(0,8 h) was 65 ± 24 (5.4–332), ng ml−1 h and t1/2 was 1.0 ± 0.34 (0.40–6.0) h. There was a small but significant difference in the mean change from baseline for SBP from 0 to 6 h after NMI 861 treatment compared with placebo (0.8 ± 1.4 vs−4.1 ± 2.1 mmHg, respectively; 95% Cl 0.0, 9.8 mmHg (P = 0.047)). There was no significant difference in SBP between treatments for the studied periods 6–12 h and 12–24 h. There was no significant difference in DBP or pulse between NMI 861 and placebo treatments for the three studied time periods. In the study designed to investigate the interaction of organic nitrate with NMI 861, subjects were infused

  18. Monitoring of Permafrost in the Hovsgol Mountain Region, Mongolia

    NASA Astrophysics Data System (ADS)

    Sharkhuu, A.; Natsagdorj, S.; Etzelmuller, B.; Heggem, E. S.; Nelson, F. E.; Shiklomanov, N.; Goulden, C.

    2005-12-01

    The Hovsgol Mountain Region is located between the coordinates of N 49°-52° and E 98°-102 ° in territory of Hovsgol Province, Mongolia. The territory is characterized by mountain permafrost, sporadic to continuous in its distribution, and occupies the southern fringe of the Siberian continuous permafrost zone. The main goal of permafrost monitoring in the region is to study recent degradation of permafrost under the influence of climate warming and human activities. Monitoring of permafrost is conducted within the framework of the Circumpolar Active Layer Monitoring (CALM) and the Global Terrestrial Network for Permafrost (GTN-P) programs. The main parameters being monitored are active layer depth and mean annual permafrost temperature at the level of the zero annual amplitude. Long-term CALM and GTN-P programs are based on ground temperature measurements in shallow to deep boreholes. Each borehole for monitoring is installed using instrumentation designed specifically to protect against air convection in them. Temperature measurements in the boreholes are made using identical thermo-resistors at corresponding depths, and carried out on the same dates each year. In addition, temperature dataloggers and thaw tubes are installed in most of the boreholes. At present, there are eight long-term (15-35 years) CALM and GTN-P active borehole sites. Boreholes are located in the Sharga valley (southwest), Burehkhan and Hovsgol phosphorite areas and Hatgal village (central part of the region) and in the Darhad depression. Initial results of the long term monitoring show that average rates of increase in active layer depth and mean annual permafrost temperature under influence of recent climate warming in the Hovsgol Mountain Region are 5-15 cm and 0.15-0.25°C per decade, respectively. The rate of permafrost degradation in bedrock is greater than in unconsolidated sediments, in ice-poor sediments more than ice-rich ones, and on north-facing slopes more than on south

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

    NASA Astrophysics Data System (ADS)

    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

    2016-04-01

    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.

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

    PubMed Central

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

    2016-01-01

    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

  1. 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

    PubMed Central

    Mahdi, Elrashid Saleh; Noor, Azmin Mohd; Sakeena, Mohamed Hameem; Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Sattar, Munavvar Abdul

    2011-01-01

    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, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. Conclusion The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can

  2. Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache

    PubMed Central

    Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.

    2014-01-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523

  3. Effect of a short-acting NO donor on bubble formation from a saturation dive in pigs.

    PubMed

    Møllerløkken, A; Berge, V J; Jørgensen, A; Wisløff, U; Brubakk, A O

    2006-12-01

    It has previously been reported that a nitric oxide (NO) donor reduces bubble formation from an air dive and that blocking NO production increases bubble formation. The present study was initiated to see whether a short-acting NO donor (glycerol trinitrate, 5 mg/ml; Nycomed Pharma) given immediately before start of decompression would affect the amount of vascular bubbles during and after decompression from a saturation dive in pigs. A total of 14 pigs (Sus scrofa domestica of the strain Norsk landsvin) were randomly divided into an experimental (n = 7) and a control group (n = 7). The pigs were anesthetized with ketamine and alpha-chloralose and compressed in a hyperbaric chamber to 500 kPa (40 m of seawater) in 2 min, and they had 3-h bottom time while breathing nitrox (35 kPa O(2)). The pigs were all decompressed to the surface (100 kPa) at a rate of 200 kPa/h. During decompression, the inspired Po(2) of the breathing gas was kept at 100 kPa. Thirty minutes before decompression, the experimental group received a short-acting NO donor intravenously, while the control group were given equal amounts of saline. The average number of bubbles seen during the observation period decreased from 0.2 to 0.02 bubbles/cm(2) (P < 0.0001) in the experimental group compared with the controls. The present study gives further support to the role of NO in preventing vascular bubble formation after decompression.

  4. Two cobalt(III) mono-dimethylglyoximates isolated from one reaction.

    PubMed

    Czapik, Agnieszka; Gdaniec, Maria

    2010-09-01

    The reaction of cobalt(II) nitrate hexahydrate with dimethylglyoxime (DMGH(2)) and 1,10-phenanthroline (phen) in a 1:1:2 molar ratio results in two Co(III) mono-dimethylglyoximates having two chelating phen ligands in cis positions and the Co(III) atom coordinated by six N atoms in a distorted octahedral coordination geometry. The isolated products differ in the deprotonation state of the DMGH(2) ligand. In [mu-hydrogen bis(N,N'-dioxidobutane-2,3-diimine)]tetrakis(1,10-phenanthroline)cobalt(III) trinitrate ethanol disolvate 1.87-hydrate, [Co(2)(C(4)H(6)N(2)O(2))(C(4)H(7)N(2)O(2))(C(12)H(8)N(2))(4)](NO(3))(3).2C(2)H(6)O.1.87H(2)O, (I), the C(2)-symmetric cation is formed with the coordination [Co(DMG)(phen)(2)](+) cations aggregating via a very strong O(-)...H(+)...O(-) hydrogen bond with an O...O distance of 2.409 (4) A. Crystals of (I) exhibit extensive disorder of the solvent molecules, the nitrate anions and one of the phen ligands. Compound (I) is a kinetic product, not isolated previously from similar systems, that transforms slowly into (N-hydroxy-N'-oxidobutane-2,3-diimine)bis(1,10-phenanthroline)cobalt(III) dinitrate ethanol monosolvate 0.4-hydrate, [Co(C(4)H(7)N(2)O(2))(C(12)H(8)N(2))(2)](NO(3))(2).C(2)H(6)O.0.40H(2)O, (II), with the DMGH(-) ligand hydrogen bonded to one of the nitrate anions. In (II), the solvent molecules and one of the nitrate anions are disordered.

  5. Metabolic engineering of Arabidopsis for butanetriol production using bacterial genes.

    PubMed

    Abdel-Ghany, Salah E; Day, Irene; Heuberger, Adam L; Broeckling, Corey D; Reddy, Anireddy S N

    2013-11-01

    1,2,4-butanetriol (butanetriol) is a useful precursor for the synthesis of the energetic material butanetriol trinitrate and several pharmaceutical compounds. Bacterial synthesis of butanetriol from xylose or arabinose takes place in a pathway that requires four enzymes. To produce butanetriol in plants by expressing bacterial enzymes, we cloned native bacterial or codon optimized synthetic genes under different promoters into a binary vector and stably transformed Arabidopsis plants. Transgenic lines expressing introduced genes were analyzed for the production of butanetriol using gas chromatography coupled to mass spectrometry (GC-MS). Soil-grown transgenic plants expressing these genes produced up to 20 µg/g of butanetriol. To test if an exogenous supply of pentose sugar precursors would enhance the butanetriol level, transgenic plants were grown in a medium supplemented with either xylose or arabinose and the amount of butanetriol was quantified. Plants expressing synthetic genes in the arabinose pathway showed up to a forty-fold increase in butanetriol levels after arabinose was added to the medium. Transgenic plants expressing either bacterial or synthetic xylose pathways, or the arabinose pathway showed toxicity symptoms when xylose or arabinose was added to the medium, suggesting that a by-product in the pathway or butanetriol affected plant growth. Furthermore, the metabolite profile of plants expressing arabinose and xylose pathways was altered. Our results demonstrate that bacterial pathways that produce butanetriol can be engineered into plants to produce this chemical. This proof-of-concept study for phytoproduction of butanetriol paves the way to further manipulate metabolic pathways in plants to enhance the level of butanetriol production.

  6. High-Performance Monopropellants and Catalysts Evaluated

    NASA Technical Reports Server (NTRS)

    Reed, Brian D.

    2004-01-01

    The NASA Glenn Research Center is sponsoring efforts to develop advanced monopropellant technology. The focus has been on monopropellant formulations composed of an aqueous solution of hydroxylammonium nitrate (HAN) and a fuel component. HAN-based monopropellants do not have a toxic vapor and do not need the extraordinary procedures for storage, handling, and disposal required of hydrazine (N2H4). Generically, HAN-based monopropellants are denser and have lower freezing points than N2H4. The performance of HAN-based monopropellants depends on the selection of fuel, the HAN-to-fuel ratio, and the amount of water in the formulation. HAN-based monopropellants are not seen as a replacement for N2H4 per se, but rather as a propulsion option in their own right. For example, HAN-based monopropellants would prove beneficial to the orbit insertion of small, power-limited satellites because of this propellant's high performance (reduced system mass), high density (reduced system volume), and low freezing point (elimination of tank and line heaters). Under a Glenn-contracted effort, Aerojet Redmond Rocket Center conducted testing to provide the foundation for the development of monopropellant thrusters with an I(sub sp) goal of 250 sec. A modular, workhorse reactor (representative of a 1-lbf thruster) was used to evaluate HAN formulations with catalyst materials. Stoichiometric, oxygen-rich, and fuelrich formulations of HAN-methanol and HAN-tris(aminoethyl)amine trinitrate were tested to investigate the effects of stoichiometry on combustion behavior. Aerojet found that fuelrich formulations degrade the catalyst and reactor faster than oxygen-rich and stoichiometric formulations do. A HAN-methanol formulation with a theoretical Isp of 269 sec (designated HAN269MEO) was selected as the baseline. With a combustion efficiency of at least 93 percent demonstrated for HAN-based monopropellants, HAN269MEO will meet the I(sub sp) 250 sec goal.

  7. Using Internet-Based Robotic Telescopes to Engage Non-Science Majors in Astronomical Observation

    NASA Astrophysics Data System (ADS)

    Berryhill, K. J.; Coble, K.; Slater, T. F.; McLin, K. M.; Cominsky, L. R.

    2013-12-01

    Responding to national science education reform documents calling for students to have more opportunities for authentic research experiences, several national projects have developed online telescope networks to provide students with Internet-access to research grade telescopes. The nature of astronomical observation (e.g., remote sites, expensive equipment, and odd hours) has been a barrier in the past. Internet-based robotic telescopes allow scientists to conduct observing sessions on research-grade telescopes half a world away. The same technology can now be harnessed by STEM educators to engage students and reinforce what is being taught in the classroom, as seen in some early research in elementary schools (McKinnon and Mainwaring 2000 and McKinnon and Geissinger 2002), middle/high schools (Sadler et al. 2001, 2007 and Gehret et al. 2005) and undergraduate programs (e.g., McLin et al. 2009). This project looks at the educational value of using Internet-based robotic telescopes in a general education introductory astronomy course at the undergraduate level. Students at a minority-serving institution in the midwestern United States conducted observational programs using the Global Telescope Network (GTN). The project consisted of the use of planetarium software to determine object visibility, observing proposals (with abstract, background, goals, and dissemination sections), peer review (including written reviews and panel discussion according to NSF intellectual merit and broader impacts criteria), and classroom presentations showing the results of the observation. The GTN is a network of small telescopes funded by the Fermi mission to support the science of high energy astrophysics. It is managed by the NASA E/PO Group at Sonoma State University and is controlled using SkyNet. Data includes course artifacts (proposals, reviews, panel summaries, presentations, and student reflections) for six semesters plus student interviews. Using a grounded theory approach

  8. Permafrost and the International Polar Year

    NASA Astrophysics Data System (ADS)

    Brown, J.; Boelhouwers, J.; Rachold, V.; Christiansen, H. H.

    2005-12-01

    Three permafrost projects are in the planning stages for 2007-2008 IPY. (1) The Permafrost Observatory Project: A Contribution to the Thermal State of Permafrost (TSP) will obtain a "snapshot" of permafrost temperatures in existing and new boreholes throughout both hemispheres. The project is a field campaign of the existing Global Terrestrial Network on Permafrost (GTN-P) that also includes the Circumpolar Active Layer Monitoring (CALM) project. (2) The Antarctic and sub-Antarctic Permafrost, Periglacial and Soil Environments project (ANTPAS) is aimed at integrating existing and new data on the distribution, thickness, age, history and physical and geochemical properties of permafrost, soils and the active-layer on the Antarctic continent and sub-Antarctic islands. A monitoring network, a regional subset of GTN-P and consisting of borehole temperatures, active-layer thickness, and periglacial and soil observations, will be established along selected environmental gradients. (3) The Arctic Circum-Polar Coastal Observatory Network (ACCO-Net) proposes to investigate approximately 20 key coastal sites including deltas and estuaries of major Siberian and North American rivers at which physical, ecological, biochemical and socio-economic changes will be observed. Both educational outreach and data management activities are key elements in the three projects and will contribute to the overall IPY goals and its legacy. Our Permafrost Legacy is to create the basis for a new generation of researcher and the "snapshot" of existing conditions as a baseline for future change assessment. The Joint Committee of the IPY has approved the three projects that include approximately 150 individuals from the 25- member International Permafrost Association (IPA). The IPA is coordinating these projects in cooperation with the International Union of Geological Sciences (IUGS), the Scientific Committee for Antarctic Research (SCAR), the Land-Ocean Interactions in the Coastal Zone (LOICZ

  9. The management and outcome of women with post-hydatidiform mole ‘low-risk' gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l−1

    PubMed Central

    McGrath, S; Short, D; Harvey, R; Schmid, P; Savage, P M; Seckl, M J

    2010-01-01

    Background: Gestational trophoblastic neoplasia (GTN) after a hydatidiform mole is either treated with single- or multi-agent chemotherapy determined by a multifactorial scoring system. Women with human chorionic gonadotrophin (hCG) levels >100 000 IU l−1 can remain within the low-risk/single-agent category and usually choose one drug therapy. Here we compare the success and duration of single- vs multi-agent chemotherapy in this patient group. Methods: Between 1980 and 2008, 65 women had a pre-treatment hCG >100 000 IU l−1 and were low risk. The initial hCG level, treatment regimens, changes and duration and overall survival were recorded. Results: Of 37 patients starting low-risk/single-agent treatment, 11 (29.7%) were treated successfully, whereas 26 (70.3%) required additional multi-agent chemotherapy to achieve complete remission (CR). Combination chemotherapy was initially commenced in 28 women, and 2 (7%) required additional drugs for CR. The overall duration of therapy for those commencing and completing single- or multi-agent chemotherapy was 130 and 123 days (P=0.78), respectively. The median-treatment duration for patients commencing single-agent but changing to multi-agent chemotherapy was 13 days more than those receiving high-risk treatment alone (136 vs 123 days; P=0.07). All 3 patients with an initial hCG >400 000 IU l−1 and treated with single-agent therapy developed drug resistance. Overall survival for all patients was 100%. Conclusion: Low-risk post-molar GTN patients with a pre-treatment hCG >100 000 and <400 000 IU l−1 can be offered low-risk single-agent therapy, as this will cure 30%, is relatively non-toxic and only prolongs treatment by 2 weeks if a change to combination agents is required. Patients whose hCG is >400 000 IU l−1 should receive multi-agent chemotherapy from the outset. PMID:20160727

  10. Global Cryosphere Watch: A New WMO Initiative

    NASA Astrophysics Data System (ADS)

    Goodison, B.; Ryabinin, V.; Asrar, G.; Yang, D.

    2008-12-01

    Legacy of the IPY 2007-2008 will take many forms, and one key legacy for the cryosphere is the development of a WMO Global Cryosphere Watch (GCW), a proposal welcomed by the 15th WMO Congress (May 2007). GCW involves research, monitoring, assessment, product development and prediction. It will cover all aspects of the cryosphere. GCW would contribute to WMO's integrated observing and information systems and the GCOS (Global Climate Observing System), like the Global Atmosphere Watch does. It will be an intergovernmental mechanism for supporting key cryospheric in situ and remote sensing observations implementing the recommendations of the IGOS Cryosphere Theme. GCW will provide reliable, comprehensive observations of the elements of the cryosphere through an integrated observing approach on global and regional scales, in collaboration with other international programmes and agencies. It will work with, and build on existing programs, such as the GTN-G and GTN-P (Global Terrestrial Networks for Glaciers / for Permafrost) and work with external partners such as space agencies and World Data Centers for Glaciology. GCW can provide an integrating mechanism required to ensure better quality data and metadata, comparison of algorithms, the means to provide the scientific community to predict the future state of the cryosphere, facilitate assessment of changes in the cryosphere and their impact, and use this information to aid the detection of climate change, and organize assessments of changes in regional and global components of the cryosphere to support decision making and policy development. GCW is envisioned to include "cold GAW-like stations" - key stations/sites working on a coherently agreed program on monitoring of changes in all components of the cryosphere, producing valuable long- term records, covering key areas of the globe with cryospheric observations. It will help existing elements function better and contribute to a global system, and will help IPY

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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.

  12. Incorporation in lipid microparticles of the UVA filter, butyl methoxydibenzoylmethane combined with the UVB filter, octocrylene: effect on photostability.

    PubMed

    Scalia, Santo; Mezzena, Matteo

    2009-01-01

    The aim of this study was to reduce the photoinstability of butyl methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by incorporating it in lipid microparticles (LMs) alone or together with the UVB filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion technique, using glyceryl behenate as lipid material and poloxamer 188 as surfactant. The LMs were characterized by release studies, scanning electron microscopy, and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2% and 10.6%, respectively. In order to reproduce the conditions prevalent in commercial sunscreen products, the photoprotective efficacy of the LMs was evaluated after their introduction in a model cream (oil-in-water emulsion) containing a mixture of UVA and UVB filters. A small but statistically significant decrease in BMDBM photodegradation was obtained when the UVA filter was encapsulated alone into the LMs (the extent of degradation was 28.6% +/-2.4 for non-encapsulated BMDBM and 26.0% +/-2.5 for BMDBM-loaded microparticles). On the other hand, the co-loading of OCR in the LMs produced a more marked reduction in the light-induced decomposition of microencapsulated BMDBM (the UVA filter loss was 21.5% +/-2.2). Therefore, incorporation in lipid microparticles of BMDBM together with the sunscreen OCR is more effective in enhancing the UVA filter photostability than LMs loaded with BMDBM alone.

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

    PubMed

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

    2015-02-20

    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.

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

    PubMed Central

    Roy, Amitava; Haldar, Sudipto; Mondal, Souvik; Ghosh, Tapan Kumar

    2010-01-01

    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 (P < .07) and feed conversion ratio (P < .05) in 39 days were higher in the E1 dietary group. Gain: ME intake and gain: protein intake during the grower phase improved quadratically (P < .05). Gross carcass traits were not affected. Body fat content and fat accretion increased (P < .05) and liver fat content decreased (P < .05) linearly with the level of emulsifier in diet. Fat excretion decreased (P < .001) leading to increased ileal fat digestibility (P < .06) in the E1 group (quadratic response). Metabolizable intake of N (P < .1) and fat (P < .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. PMID:20671938

  15. 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.

    PubMed

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

    2017-03-21

    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. This method developed has been applied to the quantitation of fatty acid methyl esters from free fatty acid and glycerolipid fractions of algae Scenedesmus dimorphus. This article is protected by copyright. All rights reserved.

  16. Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid α-glycosyltransferase

    PubMed Central

    Sobhanifar, Solmaz; Worrall, Liam James; Gruninger, Robert J.; Wasney, Gregory A.; Blaukopf, Markus; Baumann, Lars; Lameignere, Emilie; Solomonson, Matthew; Brown, Eric D.; Withers, Stephen G.; Strynadka, Natalie C. J.

    2015-01-01

    Unique to Gram-positive bacteria, wall teichoic acids are anionic glycopolymers cross-stitched to a thick layer of peptidoglycan. The polyol phosphate subunits of these glycopolymers are decorated with GlcNAc sugars that are involved in phage binding, genetic exchange, host antibody response, resistance, and virulence. The search for the enzymes responsible for GlcNAcylation in Staphylococcus aureus has recently identified TarM and TarS with respective α- and β-(1–4) glycosyltransferase activities. The stereochemistry of the GlcNAc attachment is important in balancing biological processes, such that the interplay of TarM and TarS is likely important for bacterial pathogenicity and survival. Here we present the crystal structure of TarM in an unusual ternary-like complex consisting of a polymeric acceptor substrate analog, UDP from a hydrolyzed donor, and an α-glyceryl-GlcNAc product formed in situ. These structures support an internal nucleophilic substitution-like mechanism, lend new mechanistic insight into the glycosylation of glycopolymers, and reveal a trimerization domain with a likely role in acceptor substrate scaffolding. PMID:25624472

  17. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin.

    PubMed

    Subedi, Robhash Kusam; Kang, Keon Wook; Choi, Hoo-Kyun

    2009-06-28

    Solid lipid nanoparticles (SLN) loaded with doxorubicin were prepared by solvent emulsification-diffusion method. Glyceryl caprate (Capmul)MCM C10) was used as lipid core, and curdlan as the shell material. Dimethyl sulfoxide (DMSO) was used to dissolve both lipid and drug. Polyethylene glycol 660 hydroxystearate (Solutol)HS15) was employed as surfactant. Major formulation parameters were optimized to obtain high quality nanoparticles. The mean particle size measured by photon correlation spectroscopy (PCS) was 199nm. The entrapment efficiency (EE) and drug loading capacity (DL), determined with fluorescence spectroscopy, were 67.5+/-2.4% and 2.8+/-0.1%, respectively. The drug release behavior was studied by in vitro method. Cell viability assay showed that properties of SLN remain unchanged during the process of freeze-drying. Stability study revealed that lyophilized SLN were equally effective (p<0.05) after 1 year of storage at 4 degrees C. In conclusion, SLN with small particle size, high EE, and relatively high DL for doxorubicin can be obtained by this method.

  18. Solid lipid microparticles containing the sunscreen agent, octyl-dimethylaminobenzoate: effect of the vehicle.

    PubMed

    Tursilli, Rosanna; Piel, Géraldine; Delattre, Luc; Scalia, Santo

    2007-06-01

    Solid lipid microparticles (SLMs) loaded with the sunscreen agent, octyl-dimethylaminobenzoate (ODAB), were prepared in order to achieve enhanced sunscreen photostability. The microparticles were produced by the melt dispersion technique using glyceryl behenate as lipidic material and poloxamer 188 as the emulsifier. The obtained SLMs showed proper features in terms of morphology, size distribution (1.67-15.81 microm) and ODAB loading (16.15+/-0.11%, w/w). The sunscreen release from the SLMs was slower than its dissolution rate and the photodecomposition of ODAB was markedly decreased (>51.3%) by encapsulation into the lipid microparticles. The efficacy of the SLM carrier system was also evaluated after their introduction in model topical formulations (i.e., hydrogel and oil-in-water emulsion). Further in vitro release measurements, performed using Franz diffusion cells with polycarbonate membranes, indicated that the retention capacity of the microparticles was lost after their incorporation into the emulsion, whereas it was retained in the hydrogel. Moreover, the SLMs achieved a reduction of the sunscreen photodegradation in the hydrogel vehicle (the ODAB loss decreased from 87.4% to 59.1%), whereas no significant photoprotective effect was observed in the emulsion. Therefore, the efficacy of the ODAB-loaded SLMs was markedly affected by the vehicle.

  19. Production of hybrid lipid-based particles loaded with inorganic nanoparticles and active compounds for prolonged topical release.

    PubMed

    García-González, C A; Sampaio da Sousa, A R; Argemí, A; López Periago, A; Saurina, J; Duarte, C M M; Domingo, C

    2009-12-01

    The production of particulate hybrid carriers containing a glyceryl monostearate (Lumulse GMS-K), a waxy triglyceride (Cutina HR), silanized TiO(2) and caffeine were investigated with the aim of producing sunscreens with UV-radiation protection properties. Particles were obtained using the supercritical PGSS (Particles from Gas Saturated Solutions) technique. This method takes advantages of the lower melting temperatures of the lipids obtained from the dissolution of CO(2) in the bulk mixture. Experiments were performed at 13 MPa and 345 K, according to previous melting point measurements. Blends containing Lumulse GMS-K and Cutina HR lipids (50 wt%) were loaded with silanized TiO(2) and caffeine in percentile proportions of 6 and 4 wt%, respectively. The particles produced were characterized using several analytical techniques as follows: system crystallinity was checked by X-ray diffraction and differential scanning calorimetry, thermal stability by thermogravimetric analysis, and morphology by scanning and transmission electron microscopy. Further, the UV-shielding ability of TiO(2) after its dispersion in the lipidic matrix was assessed by solid UV-vis spectroscopy. Preliminary results indicated that caffeine-loaded solid lipid particles presented a two-step dissolution profile, with an initial burst of 60 wt% of the loaded active agent. Lipid blends loaded with TiO(2) and caffeine encompassed the UV-filter behavior of TiO(2) and the photoaging prevention properties of caffeine.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

    2014-05-01

    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.

  2. Characterization of Silver Nanoparticles in Cell Culture Medium Containing Fetal Bovine Serum.

    PubMed

    Hansen, Ulf; Thünemann, Andreas F

    2015-06-23

    Nanoparticles are being increasingly used in consumer products worldwide, and their toxicological effects are currently being intensely debated. In vitro tests play a significant role in nanoparticle risk assessment, but reliable particle characterization in the cell culture medium with added fetal bovine serum (CCM) used in these tests is not available. As a step toward filling this gap, we report on silver ion release by silver nanoparticles and on changes in the particle radii and in their protein corona when incubated in CCM. Particles of a certified reference material, p1, and particles of a commercial silver nanoparticle material, p2, were investigated. The colloidal stability of p1 is provided by the surfactants polyethylene glycol-25 glyceryl trioleate and polyethylene glycol-20 sorbitan monolaurate, whereas p2 is stabilized by polyvinylpyrrolidone. Dialyses of p1 and p2 reveal that their silver ion release rates in CCM are much larger than in water. Particle characterization was performed with asymmetrical flow field-flow fractionation, small-angle X-ray scattering, dynamic light scattering, and electron microscopy. p1 and p2 have similar hydrodynamic radii of 15 and 16 nm, respectively. The silver core radii are 9.2 and 10.2 nm. Gel electrophoresis and subsequent peptide identification reveal that albumin is the main corona component of p1 and p2 after incubation in CCM that consists of Dulbecco's modified Eagle medium with 10% fetal bovine serum added.

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    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.

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

    PubMed

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

    2016-06-01

    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.

  5. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

    NASA Astrophysics Data System (ADS)

    Niculae, G.; Lacatusu, I.; Badea, N.; Meghea, A.

    2012-08-01

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.

  6. Doxycycline hyclate-loaded bleached shellac in situ forming microparticle for intraperiodontal pocket local delivery.

    PubMed

    Phaechamud, Thawatchai; Chanyaboonsub, Nuttapong; Setthajindalert, Orn

    2016-10-10

    Bleached shellac (BS) is a water-insoluble polyester resin made up of sesquiterpenoid acids esterified with hydroxy aliphatic acids. In this study, BS dissolved in N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO) and 2-pyrrolidone was used as the internal phase of oil in oil emulsion using olive oil emulsified with glyceryl monostearate (GMS) as the external phase of in situ forming microparticles (ISM). Doxycycline hyclate (DH)-loaded BS ISMs were tested for emulsion stability, viscosity, rheology, transformation into microparticles, syringeability, drug release, surface topography, in vitro degradation and antimicrobial activities against Staphylococcus aureus, Streptococcus mutans and Porphyromonas gingivalis. All emulsions exhibited pseudoplastic flow and notably low syringeability force. Slower transformation from emulsion into microparticles of ISM prepared with 2-pyrrolidone was owing to slower solvent exchange of this solvent which promoted less porous structure of obtained BS matrix microparticles. The system containing 2-pyrrolidone exhibited a higher degradability than that prepared with DMSO. Developed DH-loaded BS ISMs exhibited a sustainable drug release for 47days with Fickian diffusion and effectively inhibited P. gingivalis, S. mutans and S. aureus. Therefore a DH-loaded BS ISM using olive oil containing GMS as the external phase and 2-pyrrolidone as a solvent was a suitable formulation for periodontitis treatment.

  7. Importance of hydrophobic interaction between a SoxB-type cytochrome c oxidase with its natural substrate cytochrome c-551 and its mutants.

    PubMed

    Kagekawa, Sayaka; Mizukami, Makoto; Noguchi, Shunsuke; Sakamoto, Junshi; Sone, Nobuhito

    2002-08-01

    Cytochrome c-551, the electron donor of SoxB-type cytochrome c oxidase in thermophilic bacilli, can be over-expressed in Bacillus thermodenitrificans cells by tranformation with pSTEc551. Several mutant cytochromes c-551 were prepared by site-directed mutagenesis to this expression plasmid. Among them, several Lys residues were changed to Ala/Ser, and we found that these mutant cytochromes retained their activity as substrates, although their K(m) values were 0.04-0.12 microM, depending on the site replaced. In contrast, the C19A mutant cytochrome, which was produced in Brevibacillus choshinensis as a secretion protein, lost its activity as a substrate, suggesting that the fatty acyl-glyceryl residue covalently bound to the cysteine residue of the wild-type c-551 plays a very important role in the activity. The importance of the hydrophobic fatty acid residue for the binding of cytochrome c-551 to the oxidase was also shown by the loss of substrate activity in deacylated cytochrome c-551. These results show the importance of the hydrophobic interaction between this cytochrome and SoxB-type oxidase, despite the fact that the importance of an electrostatic interaction between cytochrome c and mitochondrial cytochrome aa(3) oxidase has already been established.

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

    PubMed

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

    2014-12-01

    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.

  9. Effect of liquid crystals with cyclodextrin on the bioavailability of a poorly water-soluble compound, diosgenin, after its oral administration to rats.

    PubMed

    Okawara, Masaki; Hashimoto, Fumie; Todo, Hiroaki; Sugibayashi, Kenji; Tokudome, Yoshihiro

    2014-09-10

    Diosgenin, found in wild yam (Dioscorea villosa), has been shown to ameliorate diabetes and hyperlipidemia, increase cell proliferation in a human 3D skin model, and inhibits melanin production in B16 melanoma cells. It is also an active element in cosmeceutical and dietary supplements. Although the bioavailability of diosgenin is low due to its poor solubility and intestinal permeability, it was subsequently improved using a β-cyclodextrin (β-CD) inclusion complex. Recently liquid crystals (LCs) were shown to enhance the bioavailability of poorly water-soluble drugs. The purpose in the present study was to prepare diosgenin LCs and investigate the interaction between LC and β-CD in order to improve its bioavailability of diosgenin. Crystallinity and particle diameters of LCs in water were determined by small angle X-ray scattering (SAXS) and Zetasizer. Pharmacokinetic parameters were calculated using the plasma content of diosgenin after its oral administration to Wistar rats. Regarding the formation of glyceryl monooleate (GMO) and phytantriol (PHY) LC, SAXS patterns showed the hexagonal and cubic phases, respectively. Bioavailability was significantly enhanced after oral administration of LCs prepared by GMO than after diosgenin alone. The bioavailability was further improved with the combination of LC and β-CD than LC and water.

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

    PubMed Central

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

    2011-01-01

    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. PMID:21915852

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

    PubMed

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

    2010-11-01

    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.

  12. Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608

    PubMed Central

    2013-01-01

    Streptomyces griseus DSM 2608 produces bafilomycin, an antifungal plecomacrolide antibiotic. We cloned and sequenced an 87.4-kb region, including a polyketide synthase (PKS) region, methoxymalonate genes, flavensomycinate genes, and other putative regulatory genes. The 58.5kb of PKS region consisting 12 PKS modules arranged in five different PKS genes, was assumed to be responsible for the biosynthesis of plecomacrolide backbone including 16-membered macrocyclic lactone. All the modules showed high similarities with typical type I PKS genes. However, the starting module of PKS gene was confirmed to be specific for isobutyrate by sequence comparison of an acyltransferase domain. In downstream of PKS region, the genes for methoxymalonate biosynthesis were located, among which a gene for FkbH-like protein was assumed to play an important role in the production of methoxymalonyl-CoA from glyceryl-CoA. Further the genes encoding flavensomycinyl-ACP biosynthesis for the post-PKS tailoring were also found in the upstream of PKS region. By gene disruption experiments of a dehydratase domain of module 12 and an FkbH-like protein, this gene cluster was confirmed to be involved in the biosynthesis of bafilomycin. PMID:23663353

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

    PubMed

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

    2014-12-01

    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.

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

    PubMed Central

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    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. PMID:24421641

  15. Antimicrobial effects of sanitizers against planktonic and sessile Listeria monocytogenes cells according to the growth phase.

    PubMed

    Chavant, Patrick; Gaillard-Martinie, Brigitte; Hébraud, Michel

    2004-07-15

    This study was designed to investigate the individual or combined effects of sanitizers on survival of planktonic or sessile Listeria monocytogenes cells at different phase of growth. The sanitizers tested included: (i) acetic acid (pH 5.0), (ii) NaOH (pH 12.0), (iii) 10% Na2SO4, (iv) 10% Na2SO4 and acetic acid (pH 5.0), (v) 10% Na2SO4 and NaOH (pH 12.0), (vi) a quaternary ammonium (20 ppm) and (vii) glyceryl monolaurate (75 ppm). Results revealed a great efficacy of alkaline treatments on both sessile and planktonic cells with a slightly higher resistance of 6 h biofilms. Quaternary ammonium appeared very effective in killing more than 98% of cells, but a resistance of 7 days biofilm was observed. Other sanitizers did not succeed in inhibiting totally the pathogen but acted in a similar way on both sessile and planktonic cells. Renewing the medium or not do not seem to be the major cause of a resistance emergence.

  16. Effect of Liquid Crystalline Systems Containing Antimicrobial Compounds on Infectious Skin Bacteria.

    PubMed

    Souza, Carla; Watanabe, Evandro; Aires, Carolina Patrícia; Lara, Marilisa Guimarães

    2016-12-27

    This study aimed (i) to prepare liquid crystalline systems (LCS) of glyceryl monooleate (GMO) and water containing antibacterial compounds and (ii) to evaluate their potential as drug delivery systems for topical treatment of bacterial infections. Therefore, LCS containing CPC (cetylpyridinium chloride) (LCS/CPC) and PHMB (poly(hexamethylene biguanide) hydrochloride) (LCS/PHMB) were prepared and the liquid crystalline phases were identified by polarizing light microscopy 24 h and 7 days after preparation. The in vitro drug release profile and in vitro antibacterial activity of the systems were assessed using the double layer agar diffusion method against Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Escherichia coli, and Enterococcus faecalis. The interaction between GMO and the drugs was evaluated by a drug absorption study. Stable liquid crystalline systems containing CPC and PHMB were obtained. LCS/PHMB decreased the PHMB release rate and exerted strong antibacterial activity against all the investigated bacteria. In contrast, CPC interacted with GMO so strongly that it became attached to the system; the amount released was not sufficient to exert antibacterial activity. Therefore, the studied liquid crystalline systems were suitable to deliver PHMB, but not CPC. Accordingly, it was demonstrated that GMO interacts with each drug differently, which may interfere in the final efficiency of GMO/water LCS.

  17. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

    PubMed Central

    Rajabalaya, Rajan; Leen, Guok; Chellian, Jestin; Chakravarthi, Srikumar; David, Sheba R.

    2016-01-01

    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. PMID:27589789

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

    PubMed Central

    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

    2014-01-01

    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

  19. Rational design of solid catalysts for the selective use of glycerol as a natural organic building block.

    PubMed

    Jérôme, François; Pouilloux, Yannick; Barrault, Joël

    2008-01-01

    Glycerol is the main co-product of the vegetable oils industry (especially biodiesel). With the rapid development of oleochemistry, the production of glycerol is rapidly increasing and chemists are trying to find new applications of glycerol to encourage a better industrial development of vegetable oils. In this Review, attention is focused on the selective use of glycerol as a safe organic building block for organic chemistry. An overview is given of the different heterogeneous catalytic routes developed by chemists for the successful and environmentally friendly use of glycerol in sustainable organic chemistry. In particular, the effects of different catalyst structural parameters are discussed to clearly highlight how catalysis can help organic chemists to overcome the drawbacks stemming from the use of glycerol as a safe organic building block. It is shown that heterogeneous catalysis offers efficient routes for bypassing the traditional use of highly toxic and expensive epichlorohydrin, 3-chloro-1,2-propanediol, or glycidol, which are usually used as a glyceryl donor in organic chemistry.

  20. Formation and characterization of microcrystalline semiconductor particles on bilayer lipid membranes

    SciTech Connect

    Baral, S.; Zhao, X.K.; Rolandi, R.; Fendler, J.H.

    1987-05-21

    Microcrystalline cadmium, indium, copper, and zinc sulfides were generated in situ on the surface of bilayer lipid membranes (BLMs) prepared from bovine-brain phosphatidylserine (PS), glyceryl monooleate (GMO), and a synthetic, polymerizable surfactant (n-C/sub 15/H/sub 31/CO/sub 2/(CH/sub 2/)/sub 2/)/sub 2/N/sup +/(CH/sub 3/)CH/sub 2/C/sub 6/H/sub 4/CH double bond CH/sub 2/, Cl/sup -/ (STYRS). Semiconductor-containing BLMs remained stable for days. Semiconductor formation on the BLM surface was monitored by optical microscopy, voltage-dependent capacitance measurements, and absorption and intracavity-laser-absorption spectroscopy. Band gap excitation of GMO- BLM-incorporated CdS resulted in the development of photovoltage. Irradiation of CdS incorporated into BLMs formed from STYRS (using a 350-nm cutoff filter) led to absorption losses due to the styrene moiety in the surfactant. Apparently, CdS sensitized the photopolymerization of STRYS BLMs.

  1. Periodic minimal surfaces

    NASA Astrophysics Data System (ADS)

    Mackay, Alan L.

    1985-04-01

    A minimal surface is one for which, like a soap film with the same pressure on each side, the mean curvature is zero and, thus, is one where the two principal curvatures are equal and opposite at every point. For every closed circuit in the surface, the area is a minimum. Schwarz1 and Neovius2 showed that elements of such surfaces could be put together to give surfaces periodic in three dimensions. These periodic minimal surfaces are geometrical invariants, as are the regular polyhedra, but the former are curved. Minimal surfaces are appropriate for the description of various structures where internal surfaces are prominent and seek to adopt a minimum area or a zero mean curvature subject to their topology; thus they merit more complete numerical characterization. There seem to be at least 18 such surfaces3, with various symmetries and topologies, related to the crystallographic space groups. Recently, glyceryl mono-oleate (GMO) was shown by Longley and McIntosh4 to take the shape of the F-surface. The structure postulated is shown here to be in good agreement with an analysis of the fundamental geometry of periodic minimal surfaces.

  2. Molecular dynamics approach to water structure of HII mesophase of monoolein

    NASA Astrophysics Data System (ADS)

    Kolev, Vesselin; Ivanova, Anela; Madjarova, Galia; Aserin, Abraham; Garti, Nissim

    2012-02-01

    The goal of the present work is to study theoretically the structure of water inside the water cylinder of the inverse hexagonal mesophase (HII) of glyceryl monooleate (monoolein, GMO), using the method of molecular dynamics. To simplify the computational model, a fixed structure of the GMO tube is maintained. The non-standard cylindrical geometry of the system required the development and application of a novel method for obtaining the starting distribution of water molecules. A predictor-corrector schema is employed for generation of the initial density of water. Molecular dynamics calculations are performed at constant volume and temperature (NVT ensemble) with 1D periodic boundary conditions applied. During the simulations the lipid structure is kept fixed, while the dynamics of water is unrestrained. Distribution of hydrogen bonds and density as well as radial distribution of water molecules across the water cylinder show the presence of water structure deep in the cylinder (about 6 Å below the GMO heads). The obtained results may help understanding the role of water structure in the processes of insertion of external molecules inside the GMO/water system. The present work has a semi-quantitative character and it should be considered as the initial stage of more comprehensive future theoretical studies.

  3. An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to isoquercitrin

    PubMed Central

    Wang, Jun; Gong, An; Yang, Cai-Feng; Bao, Qi; Shi, Xin-Yi; Han, Bei-Bei; Wu, Xiang-Yang; Wu, Fu-An

    2015-01-01

    Isoquercitrin is a rare, natural ingredient with several biological activities that is a key precursor for the synthesis of enzymatically modified isoquercitrin (EMIQ). The enzymatic production of isoquercitrin from rutin catalyzed by hesperidinase is feasible; however, the bioprocess is hindered by low substrate concentration and a long reaction time. Thus, a novel biphase system consisting of [Bmim][BF4]:glycine-sodium hydroxide (pH 9) (10:90, v/v) and glyceryl triacetate (1:1, v/v) was initially established for isoquercitrin production. The biotransformation product was identified using liquid chromatography-mass spectrometry, and the bonding mechanism of the enzyme and substrate was inferred using circular dichroism spectra and kinetic parameters. The highest rutin conversion of 99.5% and isoquercitrin yield of 93.9% were obtained after 3 h. The reaction route is environmentally benign and mild, and the biphase system could be reused. The substrate concentration was increased 2.6-fold, the reaction time was reduced to three tenths the original time. The three-dimensional structure of hesperidinase was changed in the biphase system, which α-helix and random content were reduced and β-sheet content was increased. Thus, the developed biphase system can effectively strengthen the hesperidinase-catalyzed synthesis of isoquercitrin with high yield. PMID:25731802

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

    PubMed

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

    2015-11-10

    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. 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.

    PubMed

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

    2015-04-01

    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.

  6. Hyperbranched polyglycerol-based lipids via oxyanionic polymerization: toward multifunctional stealth liposomes.

    PubMed

    Hofmann, Anna Maria; Wurm, Frederik; Hühn, Eva; Nawroth, Thomas; Langguth, Peter; Frey, Holger

    2010-03-08

    We describe the synthesis of linear-hyperbranched lipids for liposome preparation based on linear poly(ethylene glycol) (PEG) and hyperbranched polyglycerol (PG). Molecular weights were adjusted to values around 3000 g/mol with varying degrees of polymerization of the linear and the branched segments in analogy to PEG-based stealth lipids; polydispersities were generally low and below 1.3. The hydrophobic anchors were introduced into the lipid structures as initiators for the anionic polymerization of ethylene oxide and are either based on cholesterol or on different aliphatic glyceryl ethers. Complete incorporation of the apolar initiators was evidenced by MALDI-ToF analysis at all stages of the reaction. The linear-hyperbranched polyether lipid is incorporated as the polyfunctional shell in liposome formulations together with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The resulting liposomes were subsequently characterized via dynamic light scattering (DLS) and small angle neutron scattering (SANS) as well as transmission electron microscopy (TEM), demonstrating the formation of unilamellar liposomes in the size range of 40 to 50 nm.

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

    PubMed

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

    2008-11-12

    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.

  8. Synthesis and characterization of novel polymers from non-petroleum sources for use in enhanced oil recovery. Final report, July 1, 1983-June 30, 1984

    SciTech Connect

    Hogen-Esch, T.E.

    1984-01-01

    Accomplishments for the past year are discussed for grafting of acrylamide to: (1) starch and related polysaccharides; and (2) cellulose solutions. In grafting acrylamide to various polysaccharide substrates such as okra polysaccharide, yellow dextrin, waxy corn starch, potato amylose, gum arabic, the efficiency of Ce/sup 4 +/ as initiator was found to vary from 0.02 to 0.89, depending on reaction conditions. Okra polysaccharide was isolated, characterized, and evaluated for use in enhanced oil recovery. A series of experiments designed to increase the viscosifying power of certain polymers by chain extension techniques has also been conducted. Characterization of the polymers by ultracentrifugation, size exclusion chromatography, membrane filtration, multi-cell equilibrium dialysis, and rheological studies has also been done. In grafting of acrylamide to cellulose solutions the following two courses were taken: (1) dissolution of cellulose in 70% aqueous zinc chloride, followed by Ce/sup 4 +/ initiated grafting of acrylamide, and (2) introduction of a 1,2-diol substituent onto the anhydroglucose units of the cellulose chain via dissolution of cellulose in concentrated aqueous NaOH, followed by treatment with glyceryl chlorohydrin. Considerable progress has been made via both approaches. 11 refs., 1 fig., 1 tab.

  9. Wax-incorporated emulsion gel beads of calcium pectinate for intragastric floating drug delivery.

    PubMed

    Sriamornsak, Pornsak; Asavapichayont, Panida; Nunthanid, Jurairat; Luangtana-Anan, Manee; Limmatvapirat, Sontaya; Piriyaprasarth, Suchada

    2008-01-01

    The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

  10. Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

    PubMed

    Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

    2015-01-01

    The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200.

  11. Hydrophilic diol monolith for the preparation of immuno-sorbents at reduced nonspecific interactions.

    PubMed

    Gunasena, Dilani N; El Rassi, Ziad

    2011-08-01

    A polar organic polymer monolith (M1) was introduced for performing immunoaffinity chromatography (IAC) at reduced nonspecific interactions. The M1 monolith was prepared by the in situ polymerization of glyceryl methacrylate (GMM) and pentaerythritol triacrylate (PETA). Through its surface diol groups, M1 provided the functionalities to immobilize antibodies. Anti-haptoglobin antibody was used as the model antibody to study the overall behavior of the immuno monolith M1 in terms of its binding to the antigen and to evaluate its nonspecific binding with other proteins, especially the high-abundance human serum proteins. To better assess the suitability of M1 for IAC, other immuno monoliths were prepared and compared with the immuno monolith M1. Two monoliths were of the traditional ones: copolymers of (i) glycidyl methacrylate and ethylene glycol dimethacrylate (EDMA) and (ii) GMM and EDMA, referred to as M2 and M3, respectively. A fourth monolith involving the copolymerization of N-(3-aminopropyl)methacrylamide hydrochloride and EDMA (M4) was introduced to allow the site-directed immobilization of antibodies. Owing to its hydroxyl groups, the M1 exhibited negligible nonspecific hydrophobic interactions with proteins. On the other hand, M4 exhibited extensive electrostatic interactions, while the M2 and to a lesser extent M3 exhibited hydrophobic interactions.

  12. Speciation of arsenic in marine food (Anemonia sulcata) by liquid chromatography coupled to inductively coupled plasma mass spectrometry and organic mass spectrometry.

    PubMed

    Contreras-Acuña, M; García-Barrera, T; García-Sevillano, M A; Gómez-Ariza, J L

    2013-03-22

    Arsenic species have been investigated in Anemonia sulcata, which is frequently consumed food staple in Spain battered in wheat flour and fried with olive oil. Speciation in tissue extracts was carried out by anion/cation exchange chromatography with inductively coupled plasma mass spectrometry (HPLC-(AEC/CEC)-ICP-MS). Three methods for the extraction of arsenic species were investigated (ultrasonic bath, ultrasonic probe and focused microwave) and the optimal one was applied. Arsenic speciation was carried out in raw and cooked anemone and the dominant species are dimethylarsinic acid (DMA(V)) followed by arsenobetaine (AB), As(V), monomethylarsonic acid (MA(V)), tetramethylarsonium ion (TETRA) and trimethylarsine oxide (TMAO). In addition, arsenocholine (AsC), glyceryl phosphorylarsenocholine (GPAsC) and dimethylarsinothioic acid (DMAS) were identified by liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-MS). These results are interesting since GPAsC has been previously reported in marine organisms after experimental exposure to AsC, but not in natural samples. In addition, this paper reports for the first time the identification of DMAS in marine food.

  13. Silica nanoparticle stabilization of liquid crystalline lipid dispersions: impact on enzymatic digestion and drug solubilization.

    PubMed

    Bhatt, Achal B; Barnes, Timothy J; Prestidge, Clive A

    2015-01-01

    The high internal surface area and drug solubilizing capacity of liquid crystal lipids makes them promising oral drug delivery systems. Pluronic F127 is typically used to disperse highly viscous cubic liquid crystal lipids into cubosomes; however, such copolymers alter the internal structure and provide little control over enzymatic digestion. This study aimed to use hydrophilic silica nanoparticles to stabilize glyceryl monooleate (GMO) cubosomes prepared by ultrasonication. We investigate the influence of silica nanoparticles size and concentration on the physical (colloidal) and chemical (enzymatic digestion) stability, as well as in vitro solubilization of cinnarizine as a poorly soluble model drug. Silica stabilized nanostructured liquid crystal dispersions (120 nm to150 nm in diameter and zeta potentials of-30 mV to -60 mV) were successfully prepared with excellent long-term stability (<10% size change after 30 days). Silica stabilized GMO cubosomes demonstrated reduced enzymatic digestion compared to pluronic F127 stabilized cubosomes. This reduced digestion was attributed to a combination of adsorbed silica nanoparticles acting as a physical barrier and excess dispersed silica adsorbing/scavenging the lipase enzyme. Under simulated intestinal digestion conditions, silica stabilized GMO cubosomes showed a greater solubilization capacity for cinnarizine, which precipitated in non-crystalline form, in comparison to pure drug suspensions or pluronic F127 stabilized GMO cubosomes. Silica nanoparticle stabilized GMO liquid crystal dispersions are a promising oral delivery vehicle.

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

    PubMed

    Yang, Zhiwen; Chen, Meiwan; Yang, Muhua; Chen, Jian; Fang, Weijun; Xu, Ping

    2014-01-01

    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.

  15. Extension of the LOPLS-AA Force Field for Alcohols, Esters, and Monoolein Bilayers and its Validation by Neutron Scattering Experiments.

    PubMed

    Pluhackova, Kristyna; Morhenn, Humphrey; Lautner, Lisa; Lohstroh, Wiebke; Nemkovski, Kirill S; Unruh, Tobias; Böckmann, Rainer A

    2015-12-10

    The recently presented LOPLS-AA all-atom force field for long hydrocarbon chains, based on the OPLS-AA force field, was extended to alcohols, esters, and glyceryl monooleate (GMO) lipids as a model lipid. Dihedral angles were fitted against high level ab initio calculations, and ester charges were increased to improve their hydration properties. Additionally, the ester Lennard-Jones parameters were readjusted to reproduce experimental liquid bulk properties, densities, and heats of vaporization. This extension enabled the setup of LOPLS-AA parameters for GMO molecules. The properties of the lipid force field were tested for the liquid-crystalline phase of a GMO bilayer. The obtained area per lipid for GMO is in good agreement with experiment. Additionally, the lipid dynamics on the subpicosecond to the nanosecond time scale is in excellent agreement with results from time-of-flight (TOF) quasielastic neutron scattering (QENS) experiments on a multilamellar monoolein system, enabling here for the first time the critical evaluation of the short-time dynamics obtained from a molecular dynamics simulation of a membrane system.

  16. Activation of the human neutrophil respiratory burst with zymosan-activated serum.

    PubMed

    Smith, R J; Iden, S S; Bowman, B J

    1984-06-15

    Zymosan-activated serum ( ZAS ) stimulated a time- and concentration-dependent generation of superoxide anion (O-2) by human neutrophils. O-2 production was rapid with maximum generation occurring 2 minutes after cell exposure to ZAS . O-2 generation is markedly reduced if cells are not preincubated with cytochalasin B prior to contact with ZAS . The amount of O-2 produced by ZAS stimulated neutrophils was enhanced in the presence of extra-cellular calcium. However, the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy) benzoate hydrochloride (TMB-8), caused a dose-related inhibition of ZAS -elicited O-2 production. Neutrophils pretreated with ZAS were desensitized to the subsequent exposure to this stimulus. The fact that pretreatment of neutrophils with ZAS did not diminish the capacity of these cells to generate O-2 in response to 1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC),N-formyl-methionyl-leucyl-phenylalanine (FMLP) or 5(5),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4), demonstrates the stimulus specific nature of ZAS -induced desensitization. Thus, ZAS , which contains the complement-derived neutrophil activator, C5a, a naturally occurring phlogistic mediator, represents a relevant probe for investigating neutrophil function.

  17. Lipids and the malarial parasite*

    PubMed Central

    Holz, George G.

    1977-01-01

    Merozoite endocytosis initiates Plasmodium development in a vacuole bounded by an erythrocyte-derived membrane, whose asymmetrical distribution of lipids and proteins is reversed in its orientation with respect to the parasite plasma membrane. Reorientation may accompany the proliferation of the membrane associated with the parasite's growth and phagocytic and pinocytic feeding. Increases in the membrane surface area of the parasite, and in some cases of the erythrocyte, parallel parasite growth and segmentation. Augmentation of all the membrane systems of the infected erythrocyte causes the lipid content to rise rapidly, but the parasite lipid composition differs from that of the erythrocyte in many respects: it is higher in diacyl phosphatidylethanolamine, phosphatidylinositol, polyglycerol phosphatides, diacylglycerols, unesterified fatty acids, triacylglycerols, and hexadecanoic and octadecenoic fatty acids and lower in sphingomyelin, phosphatidylserine, alkoxy phosphatidylethanolamine, cholesterol, and polyunsaturated fatty acids. Active lipid metabolism accompanies the membrane proliferation associated with feeding, growth, and reproduction. Plasmodium is incapable of de novo biosynthesis of fatty acids and cholesterol; however, it can fabricate its glycerides and phosphoglycerides with host-supplied fatty acids, nitrogenous bases, alcohols, ATP, and coenzyme A, and can generate the glyceryl moiety during glycolysis. Cholesterol is obtained from the host but nothing is known of sphingolipid origins. Lipid metabolism of the parasite may be associated with alterations in the amounts of octadecenoic fatty acids and cholesterol in the erythrocyte plasma membrane, which in turn are responsible for changes in permeability and fragility. PMID:412602

  18. Nanoscale confinement effects on the relaxation dynamics in networks of diglycidyl ether of bisphenol-A and low-molecular-weight poly(ethylene oxide).

    PubMed

    Kalogeras, Ioannis M; Stathopoulos, Andreas; Vassilikou-Dova, Aglaia; Brostow, Witold

    2007-03-22

    Thermoplastic poly(ethylene oxide) (PEO) (Mw(PEO) approximately 4000) has been used to prepare thermosetting nanocomposites incorporating diglycidyl ether of bisphenol A (DGEBA) epoxy oligomer. Blends with various PEO/DGEBA weight ratios were cured using stoichiometric portions of 4,4'-diaminodiphenylmethane. The resulting semi-interpenetrating polymer networks were studied by several techniques. Nanoscale confinement effects, thermal (glass transition, melting and crystallization temperatures) and structural features of our materials are similar to those for networks with much higher Mw(PEO) and different curing agents; however, the polyether crystallization onset occurs in our case at a lower PEO concentration; shorter PEO chains organize themselves more easily into crystalline domains. Very low estimates of the k parameter of the Gordon-Taylor equation, used to fit the compositional dependences of the dielectric and calorimetric glass transition temperatures, and a strong plasticization of the motion of the glyceryl segments (beta-relaxation) in the epoxy resin were observed. These illustrate an intensified weakening in the strength of the intermolecular interactions in the modified networks, as compared to the high strength of the self-association of hydroxyls in the neat resin. The significance of hydrogen-bonding interactions between the components for obtaining structurally homogeneous thermoset-i-thermoplastic networks is discussed.

  19. Integration of chemical catalysis with extractive fermentation to produce fuels.

    PubMed

    Anbarasan, Pazhamalai; Baer, Zachary C; Sreekumar, Sanil; Gross, Elad; Binder, Joseph B; Blanch, Harvey W; Clark, Douglas S; Toste, F Dean

    2012-11-08

    Nearly one hundred years ago, the fermentative production of acetone by Clostridium acetobutylicum provided a crucial alternative source of this solvent for manufacture of the explosive cordite. Today there is a resurgence of interest in solventogenic Clostridium species to produce n-butanol and ethanol for use as renewable alternative transportation fuels. Acetone, a product of acetone-n-butanol-ethanol (ABE) fermentation, harbours a nucleophilic α-carbon, which is amenable to C-C bond formation with the electrophilic alcohols produced in ABE fermentation. This functionality can be used to form higher-molecular-mass hydrocarbons similar to those found in current jet and diesel fuels. Here we describe the integration of biological and chemocatalytic routes to convert ABE fermentation products efficiently into ketones by a palladium-catalysed alkylation. Tuning of the reaction conditions permits the production of either petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in situ selective extraction of both acetone and alcohols to enable the simple integration of ABE fermentation and chemical catalysis, while reducing the energy demand of the overall process. This process provides a means to selectively produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars at yields near their theoretical maxima.

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

    PubMed

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

    2009-01-31

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:26760943

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

    PubMed Central

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

    2016-01-01

    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 13C 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. PMID:26166447

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

    PubMed

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

    2015-08-05

    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.

  4. 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.

    PubMed

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

    2016-12-21

    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.

  5. An oral controlled release system for ambroxol hydrochloride containing a wax and a water insoluble polymer.

    PubMed

    Chi, Na; Guo, Ju Hong; Zhang, Yu; Zhang, Wei; Tang, Xing

    2010-01-01

    This study was carried out to develop and optimize oral sustained-release formulations for Ambroxol hydrochloride matrix pellets using a combination of wax and water-insoluble polymer, glyceryl behenate (Compritol 888 ATO) and Ethylcellulose (EC(7 FP)). It involved three factors: the content of Compritol 888 ATO (X(1)), EC(7 FP) (X(2)), and the matrix formation methods (X(3)), as independent variables. The drug release percentages at 1, 2 and 4 h were the target responses and were restricted to 15-45% (Y(1)), 45-80% (Y(2)) and 80-100% (Y(3)), respectively. The final blend formulation prepared by extrusion spheronization, was achieved with 27.00% (w/w) Ambroxol hydrochloride, 48.70% (w/w) Compritol 888 ATO, and 24.30% (w/w) EC(7 Fp) with 40 degrees C for 12 h. Comparing the single matrix materials consisting of just the wax or water-insoluble in the complex matrix system containing wax and water-insoluble polymer, the release of the drug can be far more retarded, when the formulations have undergone the process of heat treatment. Furthermore, the combination of the two polymers, with flexible matrix formation methods, will offer a very promising way of producing matrix pellets instead of coated controlled-release pellets to meet various demands of drug release.

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

    SciTech Connect

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

    2016-01-01

    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).

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

    NASA Astrophysics Data System (ADS)

    Nafee, N.; Schneider, M.

    2014-02-01

    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.

  8. Perhydrolase-nanotube paint composites with sporicidal and antiviral activity.

    PubMed

    Grover, Navdeep; Douaisi, Marc P; Borkar, Indrakant V; Lee, Lillian; Dinu, Cerasela Zoica; Kane, Ravi S; Dordick, Jonathan S

    2013-10-01

    AcT (perhydrolase) containing paint composites were prepared leading to broad-spectrum decontamination. AcT was immobilized onto multi-walled carbon nanotubes (MWNTs) and then incorporated into latex-based paints to form catalytic coatings. These AcT-based paint composites showed a 6-log reduction in the viability of spores of Bacillus cereus and Bacillus anthracis (Sterne) within 60 min. The paint composites also showed >4-log reduction in the titer of influenza virus (X-31) within 10 min (initially challenged with 10(7) PFU/mL). AcT-based paint composites were also tested using various perhydrolase acyl donor substrates, including propylene glycol diacetate (PGD), glyceryl triacetate, and ethyl acetate, with PGD observed to be the best among the substrates tested for generation of peracetic acid and killing of bacillus spores. The operational stability of paint composites was also studied at different relative humidities and temperatures to simulate real-life operation.

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

    PubMed

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

    2012-02-01

    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.

  10. Risk based approach for design and optimization of stomach specific delivery of rifampicin.

    PubMed

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

    2013-10-15

    The research envisaged focuses on risk management approach for better recognizing the risks, ways to mitigate them and propose a control strategy for the development of rifampicin gastroretentive tablets. Risk assessment using failure mode and effects analysis (FMEA) was done to depict the effects of specific failure modes related to respective formulation/process variable. A Box-Behnken design was used to investigate the effect of amount of sodium bicarbonate (X1), pore former HPMC (X2) and glyceryl behenate (X3) on percent drug release at 1st hour (Q1), 4th hour (Q4), 8th hour (Q8) and floating lag time (min). Main effects and interaction plots were generated to study effects of variables. Selection of the optimized formulation was done using desirability function and overlay contour plots. The optimized formulation exhibited Q1 of 20.9%, Q4 of 59.1%, Q8 of 94.8% and floating lag time of 4.0 min. Akaike information criteria and Model selection criteria revealed that the model was best described by Korsmeyer-Peppas power law. The residual plots demonstrated no existence of non-normality, skewness or outliers. The composite desirability for optimized formulation computed using equations and software were 0.84 and 0.86 respectively. FTIR, DSC and PXRD studies ruled out drug polymer interaction due to thermal treatment.

  11. Curcumin nanoemulsion for transdermal application: formulation and evaluation.

    PubMed

    Rachmawati, Heni; Budiputra, Dewa Ken; Mauludin, Rachmat

    2015-04-01

    The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350 mg curcumin/10 g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0 ± 1.5 nm, 0.18 ± 0.0 and -5.9 ± 0.3 mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.

  12. Biodiesel synthesis using calcined layered double hydroxide catalysts

    SciTech Connect

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

    2008-01-01

    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.

  13. Tricaprylin-water partition coefficients and their temperature dependence for selected chlorobenzenes

    SciTech Connect

    Bahadur, N.P.; Shiu, W.Y.; Boocock, D.G.B.; Mackay, D.

    1999-01-01

    Measurements of partition coefficients between tricaprylin (glyceryl tri-n-octanoate) and water are reported for seven chlorobenzenes (1,2-dichlorobenzene, 1,4-dichlorobenzene, 1,3,5-trichlorobenzene, 1,2,3,4-tetrachlorobenzene, 1,2,3,5-tetrachlorobenzene, pentachlorobenzene, and hexachlorobenzene) between 5 and 45 C. The values are compared with reported data on octanol-water and triolein-water partition coefficients. The van`t Hoff plots of log K{sub OW} versus T{sup {minus}1} exhibit linearity with values of K{sub OW} increasing by 5--8% over this temperature range, and the enthalpy of phase change varies from 9.7 to 16 kJ/mol. Several reasons are suggested why tricaprylin-water partition coefficients may be preferable to octanol-water and triolein-water partition coefficients when quantifying a substance`s hydrophobicity. The mutual solubilities of tricaprylin and water are less than that of octanol and water. Tricaprylin is easier to purify than triolein and, because of its lower molecular mass, is easier to analyze by gas chromatography.

  14. Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy.

    PubMed

    Jain, Vikas; Swarnakar, Nitin K; Mishra, Prabhat R; Verma, Ashwni; Kaul, Ankur; Mishra, Anil K; Jain, Narendra K

    2012-10-01

    A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2 ± 2.5% in 24 h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3 ± 10.2 to 4.4 ± 1.3%) and control the release of PTX (43.6 ± 3.2% released in 24 h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using (99m)Tc-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24 h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel.

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

    PubMed

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

    2011-07-29

    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.

  16. Acetylglyceryl ether phosphorylcholine (AGEPC; platelet-activating factor)-induced stimulation of rabbit platelets: correlation between phosphatidic acid level, 45Ca2+ uptake, and (3H)serotonin secretion

    SciTech Connect

    Shukla, S.D.; Hanahan, D.J.

    1984-08-01

    When 32P-labeled rabbits platelet were incubated with 5 X 10(-10) M 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), either in the presence or absence (0.1 mM EGTA) of added Ca2+, there was a three- to five-fold increase in the (32P)phosphatidic acid (PA) pool within 15 to 20 s. This event was followed by a gradual decrease in the (32P)PA level to near basal level in 5 min. AGEPC effected this change in (32P)PA in a characteristic dose- and time-dependent manner. Polar head group analogs of AGEPC, such as AGEDME and AGEMME, also effected an increase in PA labeling at levels comparable to those previously reported for their activity toward rabbit platelets. Other analogs, i.e., lysoGEPC and the enantiomer, sn-1-AGEPC, which are inactive toward rabbit platelets, also showed no effect on the level of (32P)PA. The finding that the PA level in rabbit platelets could be manipulated by the addition of AGEPC, without any added Ca2+, provided an excellent model system for establishing a correlation between the uptake of Ca2+, serotonin release, and PA level. Thus, PA must be regarded as a sensitive indicator of a reaction mechanism important to the platelet response to AGEPC, and could be the focal point in promoting calcium uptake during the stimulation process.

  17. Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications

    PubMed Central

    Khameneh, Bahman; Halimi, Vahid; Jaafari, Mahmoud Reza; Golmohammadzadeh, Shiva

    2015-01-01

    Objective(s): In the current study, sunscreen and moisturizing properties of solid lipid nanoparticle (SLN)-safranal formulations were evaluated. Materials and Methods: Series of SLN were prepared using glyceryl monostearate, Tween 80 and different amounts of safranal by high shear homogenization, and ultrasound and high-pressure homogenization (HPH) methods. SLN formulations were characterized for size, zeta potential, morphology, thermal properties, and encapsulation efficacy. The Sun Protection Factor (SPF) of the products was determined in vitro using transpore tape. The moisturizing activity of the products was also evaluated by corneometer. Results: The SPF of SLN-safranal formulations was increased when the amount of safranal increased. Mean particle size for all formulas was approximately 106 nm by probe sonication and 233 nm using HPH method. The encapsulation efficiency of safranal was around 70% for all SLN-safranal formulations. Conclusion: The results conclude that SLN-safranal formulations were found to be effective for topical delivery of safranal and succeeded in providing appropriate sunscreen properties. PMID:25810877

  18. Combinatorial study of ceramic tape-casting slurries.

    PubMed

    Liu, Zhifu; Wang, Yiling; Li, Yongxiang

    2012-03-12

    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.

  19. Asymmetric lipid-polymer particles (LIPOMER) by modified nanoprecipitation: role of non-solvent composition.

    PubMed

    Jindal, Anil B; Devarajan, Padma V

    2015-07-15

    Asymmetric lipid polymer nanostructures (LIPOMER) comprising glyceryl monostearate (GMS) as lipid and Gantrez AN 119 (Gantrez) as polymer, revealed enhanced splenic accumulation. In the present paper, we attempt to explain the formation of asymmetric GMS LIPOMER using real time imaging. Particles were prepared by precipitation under static conditions using different non-solvent phase compositions. The process was video recorded and the videos converted to time elapsed images using the FFmpeg 0.10.2 software at 25 frames/sec. Non-solvent compositions comprising >30% of IPA/Acetone revealed significant stranding of the solvent phase and slower onset of precipitation(2-6s). At lower concentrations of IPA and acetone, and in non-solvent compositions comprising ethanol/water the stranding phenomenon was not evident. Further, rapid precipitation(<1 s) was evident. Nanoprecipitation based on the Marangoni effect is a result of diffusion stranding, interfacial turbulence, and mass transfer of solvent and non-solvent resulting in solute precipitation. Enhanced diffusion stranding favored by high interaction of GMS and Gantrez(low ΔPol), and the low solubility parameter(Δδtotal) and high mixing enthalpy(ΔHM) of GMS in IPA resulted in droplets with random shapes analogous to an amoeba with pseudopodia, which on precipitation formed asymmetric particles. Asymmetric particles could be readily designed through appropriate selection of solutes and non-solvent phase by modified nanoprecipitation.

  20. Effects of hexagonal boron nitride on dry compression mixture of Avicel DG and Starch 1500.

    PubMed

    Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

    2016-01-01

    The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) on a (1:1) binary mixture of Avicel DG and Starch 1500 after using the dry granulation-slugging method and compare it with conventional lubricants, such as magnesium stearate (MGST), glyceryl behenate (COMP) and stearic acid (STAC). MGST is one of the most commonly used lubricants in the pharmaceutical industry. However, it has several adverse effects on tablet properties. In our current study, we employed various methods to eradicate the work hardening phenomenon in dry granulation, and used HBN as a new lubricant to overcome the adverse effects of other lubricants on tablet properties. HBN was found to be as effective as MGST and did not show any significant adverse effects on the crushing strength or work hardening. From the scanning electron microscope (SEM) images, it was concluded that HBN distributed better than MGST. As well as showing better distribution, HBN's effect on disintegration was the least pronounced. Semi-quantitative weight percent distribution of B and N elements in the tablets was obtained using EDS (energy dispersive spectroscopy). Based on atomic force microscope (AFM) surface roughness images, formulations prepared with 1% HBN showed better plastic character than those prepared with MGST.

  1. Compression parameters of hexagonal boron nitride on direct compression mixture of microcrystalline cellulose and modified starch.

    PubMed

    Halaçoğlu, Mekin Doğa; Uğurlu, Timuçin

    2015-01-01

    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 (MGST), glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied and tablets were manufactured on a single station instrumented tablet press. This study comprised the continuation of our previous one, so mixture of microcrystalline cellulose and modified starch was used as a master formula to evaluate effects of lubricants on pharmaceutical excipients that undergo complete plastic deformation without any fragmentation under compression pressure. 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 lubricant. MGST was found to be the most effective lubricant and HBN was found very close to it. HBN did not show a significant negative effect on the crushing strength and disintegration time of the tablets when we compared with MGST. Based on the Heckel plots at the level of 1%, formulation prepared with HBN showed the most pronounced plastic character.

  2. Giant papillary conjunctivitis.

    PubMed Central

    Donshik, P C

    1994-01-01

    Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 11 A FIGURE 11 B FIGURE 11 C FIGURE 11 D PMID:7886881

  3. Simple complementary liquid chromatography and mass spectrometry approaches for the characterization of triacylglycerols in Pinus koraiensis seed oil.

    PubMed

    Acheampong, Akwasi; Leveque, Nathalie; Tchapla, Alain; Heron, Sylvie

    2011-08-05

    A new simple strategy to identify triacylglycerols (TAGs) in oils and fats was performed using on line coupling of non aqueous reversed phase chromatography-electrospray ionization-mass spectrometry (NARP-LC-ESI-MS(2)) with silver nitrate (AgNO(3)) as post-column additive, and chromatographic data (partition number information and both the graphs of log k vs. number of double bond (DBN) and carbon number (CN)). NARP liquid chromatography permitted to separate TAGs composed of Δ5 and Δ9 but not from Δ11 double bond location on alkyl chain of fatty acid residues. Silver cationization improved the sensitivity by a factor one hundred. MS(2) information gave unambiguously the nature of three fatty acid residues bonded to glyceryl backbone of TAGs while log k against DBN and CN curves discriminated between the same molecular mass TAG isomers (whose constitutive fatty acid residues are double bond position and configuration isomers). Combination of structural information given by MS with chromatographic retention laws led to the development of a general methodology for determination of the structure of TAGs in lipids. This methodology was applied to Pinus koraiensis seed oil for which some uncommon TAGs are present. It permitted the identification of 58 TAGs in this oil. The experimental proof of 29 uncommon TAGs as component of this oil is demonstrated. Among them 26 were minor constituents.

  4. Production and characterization of anisotropic particles from biodegradable materials.

    PubMed

    Romanski, Francis S; Winkler, Jennifer S; Riccobene, Ryan C; Tomassone, M Silvina

    2012-02-28

    In recent years, production and characterization of anisotropic particles has become of interest in a wide range of scientific fields including polymer chemistry, drug delivery, electronics, energy, and nanotechnology. In this work, we demonstrate a novel formulation for production of anisotropic particles via an internal phase separation of biodegradable components. Specifically, binary mixtures of biodegradable polymers poly(lactic-co-glycolic acid), polycaprolactone, and biodegradable lipid Precirol (glyceryl palmitostearate) were dissolved in dichloromethane, emulsified, and prepared into anisotropic particles using a modified solvent evaporation technique. During the slow evaporation process the components self-assembled into anisotropic particles with distinct morphologies. Polymer/polymer formulations resulted in compartmentalized anisotropic heterodimer particles, while polymer/lipid combinations yielded "ice cream cone" shaped particles. It was found that addition of certain active pharmaceuticals resulted in an altered, pox-like segregation at the particle surface of polymer/polymer formulations. The anisotropic nature of the particles was subsequently characterized using optical microscopy, scanning electron microscopy, zeta potential, electrophoresis, and X-ray diffraction. Successful formulations presented here may potentially be employed as multicompartmental drug carriers with staggered drug release rates or alternatively as a colloidal excipient for an arsenal of pharmaceutical applications.

  5. Optimization of metronidazole sustained-release films using D-optimal design.

    PubMed

    Peerapattana, Jomjai; Ngamsupsiri, Teeraphat; Cheucharoenvasuchai, Nopadol; Saikaew, Charnnarong

    2015-04-30

    The aim of this study was to develop sustained-release metronidazole films for periodontal pockets using a computer-aided statistical approach. The studied independent variables were the amount of polycaprolactone, metronidazole, hydroxypropylmethyl cellulose and glyceryl monostearate. The response of interest was the cumulative percentage release of metronidazole at 1, 2, 3, 4 and 5 days. The films were prepared using a melt method. The physicochemical properties and release profiles of the films were investigated. Model validation was also performed. The produced films were thin white sheets with a smooth and glossy surface. Each sheet had an average weight of 9.31 ± 0.10mg. The metronidazole was uniformly dispersed in the film, and the percentage of drug loading was 100.12 ± 4.38%. The thickness of the film was 325 ± 5.27 μm. The puncture strength, % elongation and Young's modulus were 11.58 ± 0.51 N/mm(2), 33.51 ± 3.61%, and 0.347 ± 0.02 1N/mm(2), respectively. The actual drug release profiles of the optimal formulation films were close to the predicted responses. Metronidazole was slowly released from the matrices over a period of at least 5 days. The release mechanism of the films followed Fickian diffusion. This study demonstrates that appropriate D-optimal design and optimization techniques can be successfully used in the development of metronidazole sustained-release films.

  6. Nonequilibrium effects in self-assembled mesophase materials: unexpected supercooling effects for cubosomes and hexosomes.

    PubMed

    Dong, Yao-Da; Tilley, Adam J; Larson, Ian; Lawrence, M Jayne; Amenitsch, Heinz; Rappolt, Michael; Hanley, Tracey; Boyd, Ben J

    2010-06-01

    Polar lipids often exhibit equilibrium liquid crystalline structures in excess water, such as the bicontinuous cubic phases (Q(II)) at low temperatures and inverse hexagonal phase (H(II)) at higher temperatures. In this study, the equilibrium and nonequilibrium phase behavior of glyceryl monooleate (GMO) and phytantriol (PHYT) systems in excess water were investigated using both continuous heating and cooling cycles, and rapid temperature changes. Evolution of the phase structure was followed using small-angle X-ray scattering (SAXS). During cooling, not only was supercooling of the liquid crystalline systems by up to 25 degrees C observed, but evidence for nonequilibrium phase structures (not present on heating; such as the gyroid cubic phase only present at low water content in equilibrium) was also apparent. The nonequilibrium phases were surprisingly stable, with return to equilibrium structure for dispersed submicrometer sized particle systems taking more than 13 h in some cases. Inhibition of phase nucleation was the key to greater supercooling effects observed for the dispersed particles compared to the bulk systems. These findings highlight the need for continued study into the nonequilibrium phase structures for these types of systems, as this may influence performance in applications such as drug delivery.

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

    PubMed

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

    2014-01-01

    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.

  8. Synthesis and antitumor activity of new alkylphospholipids containing modifications of the phosphocholine moiety.

    PubMed

    Ukawa, K; Imamiya, E; Yamamoto, H; Mizuno, K; Tasaka, A; Terashita, Z; Okutani, T; Nomura, H; Kasukabe, T; Hozumi, M

    1989-05-01

    New antitumor alkylglycerophospholipids, in which primarily the phosphocholine moiety of the platelet activating factor (PAF) molecule was modified, were synthesized from 1-alkyl-2-substituted glycerols by introducing polar head phosphoryl groups having methylene bridges of various lengths (from 2 to 14 carbons). They were tested for PAF agonistic activity and antitumor properties. In a series of 1-octadecyl-2-acetoacetylglycerophospholipids (1a-f), an increase in the length of the methylene bridge separating the phosphate and trimethylammonio group in the polar head side chain at position 3 of the glycerol backbone resulted in a progressive decrease in PAF agonistic activity and a characteristic change in antitumor activity against human promyelocytic leukemia cells (HL-60). Maximal potency was obtained with the compound having a decamethylene bridge (1e, IC50 value = 1.5 microgram/ml). Thus, alkylphospholipids possessing a decamethylene bridge and a variety of substituents at position 2 (1g-n) were synthesized. They showed potent inhibitory activity with IC50 values ranging from 0.4 to 1.9 micrograms/ml, depending on the nature of the 2-substituent in the phospholipid molecule. In in vivo tests of the present series of alkylglycerophospholipids (1a--n), using mice bearing sarcoma 180 and mice with mammary carcinoma MM46 (both cells and compounds were given i.p.), 1-octadecyl-2-acetoacetyl-3-glyceryl omega-trimethylammoniodecyl phosphate (1e) showed the most potent life-prolonging effect. The structure-activity relationships are discussed.

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

    PubMed

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

    2004-08-20

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

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

    PubMed

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

    2013-01-10

    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.

  11. Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids.

    PubMed

    Pungente, Michael D; Jubeli, Emile; Øpstad, Christer L; Al-Kawaz, Mais; Barakat, Nour; Ibrahim, Tarek; Abdul Khalique, Nada; Raju, Liji; Jones, Rachel; Leopold, Philip L; Sliwka, Hans-Richard; Partali, Vassilia

    2012-03-16

    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'-dimethylaminoethane)carbamoyl]-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.

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

    PubMed

    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

    2014-08-20

    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.

  13. Computational Models of the Gastrointestinal Environment. 2. Phase Behavior and Drug Solubilization Capacity of a Type I Lipid-Based Drug Formulation after Digestion.

    PubMed

    Birru, Woldeamanuel A; Warren, Dallas B; Han, Sifei; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Chalmers, David K

    2017-03-06

    Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the gastrointestinal (GI) tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the GI microenvironment containing a digested triglyceride-based (Type I) drug formulation. Both the experimental and theoretical models consist of molecular species representing bile (glycodeoxycholic acid), digested triglyceride (1:2 glyceryl-1-monooleate and oleic acid), and water. We have characterized the phase behavior of the physical system using nephelometry, dynamic light scattering, and polarizing light microscopy and compared these measurements to phase behavior observed in multiple MD simulations. Using this model microenvironment, we have investigated the dissolution of the poorly water-soluble drug danazol experimentally using LC-MS and theoretically by MD simulation. The results show how the formulation lipids alter the environment of the GI tract and improve the solubility of danazol. The MD simulations successfully reproduce the experimental results showing the utility of MD in modeling the fate of drugs after digestion of lipid-based formulations within the intestinal lumen.

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    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). PMID:24967360

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

    PubMed

    Bodmeier, R; Wang, J; Bhagwatwar, H

    1992-01-01

    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.

  17. Formulating fluticasone propionate in novel PEG-containing nanostructured lipid carriers (PEG-NLC).

    PubMed

    Doktorovová, Slavomíra; Araújo, Joana; Garcia, Marisa L; Rakovský, Erik; Souto, Eliana B

    2010-02-01

    The aim of this study was to develop nanostructured lipid carriers (NLC) for topical delivery of fluticasone propionate (FP) with the aim to further improve the safety profile and decrease the adverse-side effects commonly reported in topical corticotherapy. NLC are colloidal drug-carriers consisting of a blend of a solid lipid and a small amount of liquid lipid since these carriers have proved to be effective in epidermal targeting in particular of glucocorticoids. NLC consisting of glyceryl palmito-stearate, and PEG-containing medium chain triglycerides mixture, stabilised by polysorbate 80 and soybean phosphatidylcholine were prepared. A mean particle size between 380 and 408 nm and entrapment efficacy of 95% were obtained for FP-loaded NLC. The crystallinity and polymorphic phase behaviour of FP-free and FP-loaded NLC were examined by differential scanning calorimetry and wide angle X-ray diffraction. Results revealed a low-crystalline structure and confirmed the incorporation of FP into the particles. The suitability of PEG-containing liquid lipids to form the lipid matrix of NLC was also confirmed.

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

    PubMed

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

    2013-05-01

    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.

  19. Unexpected skin barrier influence from nonionic emulsifiers.

    PubMed

    Bárány, E; Lindberg, M; Lodén, M

    2000-02-15

    Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.

  20. Towards Preserving the Immunogenicity of Protein Antigens Carried by Nanoparticles While Avoiding the Cold Chain

    PubMed Central

    Sloat, Brian R.; Sandoval, Michael A.; Cui, Zhengrong

    2010-01-01

    Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37°C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration. PMID:20416366

  1. Relationship between the size of nanoparticles and their adjuvant activity: Data from a study with an improved experimental design

    PubMed Central

    Li, Xinran; Sloat, Brian R.; Yanasarn, Nijaporn; Cui, Zhengrong

    2011-01-01

    There is a growing interest in identifying the relationship between the size of nanoparticles and their adjuvant activity, but the results from recent studies remain controversial. To address the controversy, it was thought that one should pay attention to the nanoparticle formulations to make sure that the antigen-loaded nanoparticles to be compared are not only different in particle size, but more importantly, as identical to each other as possible in all other formulation properties. In the present study, using ovalbumin (OVA) as a model antigen conjugated onto nanoparticles engineered from lecithin/glyceryl monostearate-in-water emulsions, we prepared OVA-nanoparticles of 230 nm and 708 nm. Before evaluating the immune responses induced by them in a mouse model, we made sure that: i) the sizes of the two OVA-nanoparticles did not extensively overlap, ii) the nanoparticles have similar zeta potentials and comparable antigen-loading, and iii) the nanoparticles did not aggregate when suspended in simulated biological media. We then showed that when subcutaneously injected into mice, the 230 nm OVA-conjugated nanoparticles induced stronger OVA-specific antibody and cellular immune responses than the 708 nm OVA-nanoparticles. Future studies attempting to correlate the size of nanoparticles and their adjuvant activities need to consider formulation parameters to ensure that the particles are different only in size and are stable before and after injection. PMID:21182941

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

    PubMed

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

    2007-09-01

    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.

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

    PubMed

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

    2016-12-15

    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. CO{sub 2}-philic oligomers as novel solvents for CO{sub 2} absorption

    SciTech Connect

    Miller, Matthew B; Luebke, David R; Enick, Robert M

    2010-01-01

    Desirable properties for an oligomeric CO{sub 2}-capture solvent in an integrated gasification combined cycle (IGCC) plant include high selectivity for CO{sub 2} over H{sub 2} and water, low viscosity, low vapor pressure, low cost, and minimal environmental, health, and safety impacts. The neat solvent viscosity and solubility of CO{sub 2}, measured via bubble-point loci and presented on a pressure−composition diagram (weight basis), and water miscibility in CO{sub 2}-philic solvents have been determined and compared to results obtained with Selexol, a commercial oligomeric CO{sub 2} solvent. The solvents tested include polyethyleneglycol dimethylether (PEGDME), polypropyleneglycol dimethylether (PPGDME), polypropyleneglycol diacetate (PPGDAc), polybutyleneglycol diacetate (PBGDAc), polytetramethyleneetherglycol diacetate (PTMEGDAc), glyceryl triacetate (GTA), polydimethyl siloxane (PDMS), and perfluorpolyether (PFPE) that has a perfluorinated propyleneglycol monomer unit. Overall, PDMS and PPGDME are the best oligomeric solvents tested and exhibit properties that make them very promising alternatives for the selective absorption of CO{sub 2} from a mixed gas stream, especially if the absorption of water is undesirable.

  5. Methods of analysis for 2-dodecylcyclobutanone and studies to support its role as a unique marker of food irradiation.

    PubMed

    Driffield, M; Speck, D; Lloyd, A S; Parmar, M; Crews, C; Castle, L; Thomas, C

    2014-03-01

    Methods of analysis for 2-dodecylcyclobutanone (2-DCB) using gas chromatography with mass spectrometric detection (GC-MS), liquid chromatography with time-of-flight mass spectrometric detection (LC-TOF-MS) and LC with tandem MS (MS/MS) detection have been developed and optimised for maximum sensitivity to allow very low irradiation doses to be detected. The LC-MS/MS method, following derivatisation with 2,4-dinitrophenylhydrazine, was found to be the most sensitive technique and was used to determine the amount of 2-DCB formed from the model compounds palmitic acid, glyceryl tripalmitate and 1,3-dipalmitoyl-2-oleoylglycerol irradiated over a range of doses by two different irradiation sources (gamma and electron beam). The model compounds were also treated with a number of non-irradiation based processing techniques including heating in the presence and absence of oxygen, light, and redox active metal salts, in a conventional oven, microwave oven and pressure cooker. No 2-DCB was detected in any of the processed non-irradiated model compounds, reaffirming the hypothesis that 2-DCB is a unique radiolytic product that can be used as a marker of irradiation in foodstuffs.

  6. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  7. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

  8. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells

    SciTech Connect

    Correll, P.H.; Fink, J.K.; Brady, R.O.; Perry, L.K.; Karlsson, S. )

    1989-11-01

    The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Four vectors were compared with respect to gene-transfer efficiency into CFU-S progenitors. One vector (G vector) required high concentrations of interleukins 3 and 6 during stimulation and coculture for efficient transduction of CFU-S progenitors. The remaining three vectors (NTG, GTN, and GI vectors) transduced these progenitors at infection frequencies approaching 100% using low concentrations of hematopoietic growth factors to simulate cell division prior to and during the infection. Vectors using the viral long terminal repeat enhancer/promoter to drive the human GC cDNA produced high levels of human GC RNA in the progeny of CFU-S progenitors after gene transfer. All three vectors producing human GC RNA in CFU-S colonies can generate human GC as detected by immunochemical analysis of CFU-S colonies. The capacity of the viral long terminal repeat and the internal thymidine kinase promoter to direct synthesis of RNA in transduced bone marrow and spleen cells 5 months after bone marrow transplantation reflected the performance of these promoters in NTG-transduced CFU-S colonies.

  9. Rapid implementation of advanced constitutive models

    NASA Astrophysics Data System (ADS)

    Starman, Bojan; Halilovič, Miroslav; Vrh, Marko; Štok, Boris

    2013-12-01

    This paper presents a methodology based on the NICE integration scheme [1, 2] for simple and rapid numerical implementation of a class of plasticity constitutive models. In this regard, an algorithm is purposely developed for the implementation of newly developed advanced constitutive models into explicit finite element framework. The methodology follows the organization of the problem state variables into an extended form, which allows the constitutive models' equations to be organized in such a way, that the algorithm can be optionally extended with minimal effort to integrate also evolution equations related to a description of other specific phenomena, such as damage, distortional hardening, phase transitions, degradation etc. To confirm simplicity of the program implementation, computational robustness, effectiveness and improved accuracy of the implemented integration algorithm, a deep drawing simulation of the cylindrical cup is considered as the case study, performed in ABAQUS/Explicit. As a fairly complex considered model, the YLD2004-18p model [3, 4] is first implemented via external subroutine VUMAT. Further, to give additional proof of the simplicity of the proposed methodology, a combination of the YLD2004-18p model and Gurson-Tvergaard-Needleman model (GTN) is considered. As demonstrated, the implementation is really obtained in a very simple way.

  10. Applications of meshless methods for damage computations with finite strains

    NASA Astrophysics Data System (ADS)

    Pan, Xiaofei; Yuan, Huang

    2009-06-01

    Material defects such as cavities have great effects on the damage process in ductile materials. Computations based on finite element methods (FEMs) often suffer from instability due to material failure as well as large distortions. To improve computational efficiency and robustness the element-free Galerkin (EFG) method is applied in the micro-mechanical constitute damage model proposed by Gurson and modified by Tvergaard and Needleman (the GTN damage model). The EFG algorithm is implemented in the general purpose finite element code ABAQUS via the user interface UEL. With the help of the EFG method, damage processes in uniaxial tension specimens and notched specimens are analyzed and verified with experimental data. Computational results reveal that the damage which takes place in the interior of specimens will extend to the exterior and cause fracture of specimens; the damage is a fast procedure relative to the whole tensing process. The EFG method provides more stable and robust numerical solution in comparing with the FEM analysis.

  11. A theoretical approach of strain localization within thin planar bands in porous ductile materials

    NASA Astrophysics Data System (ADS)

    Leblond, Jean-Baptiste; Mottet, Gérard

    2008-01-01

    Propagation of cracks in ductile materials is well known to occur through two possible mechanisms: coalescence of cavities and formation of shear bands ('void sheet mechanism'). The classical Gurson-Tvergaard-Needleman (GTN) homogenized model for such materials incorporates some phenomenological modelling of coalescence, but not of formation of shear bands assisted by the presence of microvoids, and this generates a number of shortcomings. In order to solve these difficulties, this paper presents a unified model of both coalescence and formation of shear bands in porous plastic solids, including the possible couplings between the two. Both phenomena are viewed as expressions of the same basic effect, namely strain localization within thin planar bands, the only difference being the mode of deformation. The model is first developed assuming a periodic distribution of cavities, then critically assessed through comparison with some micromechanical numerical simulations based on the same assumption, and finally extended to the case of a random distribution of voids. To cite this article: J.-B. Leblond, G. Mottet, C. R. Mecanique 336 (2008).

  12. Effects of substrate stiffness on adipogenic and osteogenic differentiation of human mesenchymal stem cells.

    PubMed

    Zhao, Wen; Li, Xiaowei; Liu, Xiaoyan; Zhang, Ning; Wen, Xuejun

    2014-07-01

    Substrate mechanical properties, in addition to biochemical signals, have been shown to modulate cell phenotype. In this study, we inspected the effects of substrate stiffness on human mesenchymal stem cells (hMSCs) derived from adult human bone marrow differentiation into adipogenic and osteogenic cells. A chemically modified extracellular matrix derived and highly biocompatible hydrogel, based on thiol functionalized hyaluronic acid (HA-SH) and thiol functionalized recombinant human gelatin (Gtn-SH), which can be crosslinked by poly (ethylene glycol) tetra-acrylate (PEGTA), was used as a model system. The stiffness of the hydrogel was controlled by adjusting the crosslinking density. Human bone marrow MSCs were cultured on the hydrogels with different stiffness under adipogenic and osteogenic conditions. Oil Red O staining and F-actin staining were applied to assess the change of cell morphologies under adipogenic and osteogenic differentiation, respectively. Gene expression of cells was determined with reverse transcription polymerase chain reaction (RT-PCR) as a function of hydrogel stiffness. Results support the hypothesis that adipogenic and osteogenic differentiation of hMSCs are inclined to occur on substrate with stiffness similar to their in vivo microenvironments.

  13. Borrelia burgdorferi EbfC defines a newly-identified, widespread family of bacterial DNA-binding proteins.

    PubMed

    Riley, Sean P; Bykowski, Tomasz; Cooley, Anne E; Burns, Logan H; Babb, Kelly; Brissette, Catherine A; Bowman, Amy; Rotondi, Matthew; Miller, M Clarke; DeMoll, Edward; Lim, Kap; Fried, Michael G; Stevenson, Brian

    2009-04-01

    The Lyme disease spirochete, Borrelia burgdorferi, encodes a novel type of DNA-binding protein named EbfC. Orthologs of EbfC are encoded by a wide range of bacterial species, so characterization of the borrelial protein has implications that span the eubacterial kingdom. The present work defines the DNA sequence required for high-affinity binding by EbfC to be the 4 bp broken palindrome GTnAC, where 'n' can be any nucleotide. Two high-affinity EbfC-binding sites are located immediately 5' of B. burgdorferi erp transcriptional promoters, and binding of EbfC was found to alter the conformation of erp promoter DNA. Consensus EbfC-binding sites are abundantly distributed throughout the B. burgdorferi genome, occurring approximately once every 1 kb. These and other features of EbfC suggest that this small protein and its orthologs may represent a distinctive type of bacterial nucleoid-associated protein. EbfC was shown to bind DNA as a homodimer, and site-directed mutagenesis studies indicated that EbfC and its orthologs appear to bind DNA via a novel alpha-helical 'tweezer'-like structure.

  14. Development, characterisation, and across-taxa utility of oil palm (Elaeis guineensis Jacq.) microsatellite markers.

    PubMed

    Billotte, N; Risterucci, A M; Barcelos, E; Noyer, J L; Amblard, P; Baurens, F C

    2001-06-01

    The results of the development of oil palm (Elaeis guineensis Jacq.) microsatellite markers are given step by step, from the screening of libraries enriched in (GA)n, (GT)n, and (CCG)n simple-sequence repeats (SSRs) to the final characterisation of 21 SSR loci. Also published are primer sequences, estimates of allele size range, and expected heterozygosity in E. guineensis and in the closely related species E. oleifera, in which an optimal utility of the SSR markers was observed. Multivariate data analyses showed the ability of SSR markers to efficiently reveal the genetic-diversity structure of the genus Elaeis in accordance with known geographical origins and with measured genetic relationships based on previous molecular studies. High levels of allelic variability indicated that E. guineensis SSRs will be a powerful tool for genetic studies of the genus Elaeis, including variety identification and intra- or inter-specific genetic mapping. PCR amplification tests on a subset of 16 other palm species and allele-sequence data showed that E. guineensis SSRs are putative transferable markers across palm taxa. In addition, phenetic information based on SSR flanking region sequences makes E. guineensis SSR markers a potentially useful molecular resource for any researcher studying the phylogeny of palm taxa.

  15. Chromosomal localisation and genetic variation of the SLC11A1 gene in goats (Capra hircus).

    PubMed

    Vacca, G M; Pazzola, M; Pisano, C; Carcangiu, V; Diaz, M L; Nieddu, M; Robledo, R; Mezzanotte, R; Dettori, M L

    2011-10-01

    The solute carrier family 11 member A1 (SLC11A1) gene is associated with resistance to infectious diseases. Chromosomal localisation, genomic regions corresponding to functional domains and the genetic variability of microsatellites in the 3' untranslated region (3'-UTR) of this gene were investigated in 427 goats (Capra hircus) of six breeds. Using dual colour fluorescence in situ hybridisation, SLC11A1 was localised to goat chromosome 2. Single strand conformation polymorphism was used to screen for polymorphisms in SLC11A1 exons 2, 10 and 15. There was no variation among goat breeds in the sarcoma homology 3 (SH3) binding motif, the protein kinase C phosphorylation site or the two N-linked glycosylation sites. Exon 15 exhibited variability due to the presence of two polymorphic microsatellites. Genotyping of the upstream guanine-thymine repeat (GTn) at 3'-UTR revealed eight alleles (GT11, GT12, GT14-GT19) in goats, whereas GT13 (present in cattle) was absent. Most goats carried the GT16 allele and no allele was found to be exclusive to only one breed. The coefficient of genetic differentiation value (G(ST)) was 0.084. This microsatellite appears to be an informative DNA marker for genetic linkage analysis in goats.

  16. Gestational Trophoblastic Disorders: An Update in 2015

    PubMed Central

    Stevens, F. T.; Katzorke, N.; Tempfer, C.; Kreimer, U.; Bizjak, G. I.; Fleisch, M. C.; Fehm, T. N.

    2015-01-01

    Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumours. They encompass premalignant disorders including complete (CHM), partial hydatidiform mole (PHM), exaggerated placental site (EPS), and placental-site nodule (PSN) as well as malignant disorders (also known as “gestational trophoblastic neoplasia [GTN]”) including invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumour (PSTT), and epitheloid trophoblastic tumours (ETT) (Fig. 1). Originally, GTD develop from abnormal proliferation of trophoblastic tissue and form botryoid arranged vesicles. Premalignant moles are usually treated by suction curettage while persistent and recurrent moles and malignant forms require systemic therapy with methotrexate or combination chemotherapy consisting of etoposide, actimomycin D, methotrexate, vincristine, and cyclophosphamide (EMA-CO). β-human chorion gonadotropin (β-hCG) plays a crucial role in diagnosis and monitoring therapeutic effects. Since the definitive diagnosis cannot be obtained by histology in most cases, persistent or recurrent disease is diagnosed by elevated or persistent serum levels of β-hCG. While curing rates are described to be as high as 98 %, GTD may initially present, recur, or end up as a metastasising systemic disease. This underlines the importance of a regular and consistent follow-up after treatment. PMID:26556906

  17. BIOCOMPATIBILITY OF A SYNTHETIC EXTRACELLULAR MATRIX ON IMMORTALIZED VOCAL FOLD FIBROBLASTS IN 3D CULTURE

    PubMed Central

    Chen, Xia

    2010-01-01

    In order to promote wound repair and induce tissue regeneration, an engineered hyaluronan (HA) hydrogel – Carbylan GSX, which contains di(thiopropionyl) bishydrazide-modified hyaluronic acid (HA-DTPH), di(thiopropionyl) bishydrazide-modified gelatin (Gtn-DTPH) and polyethylene glycol diacrylate (PEGDA), has been developed for extracellular matrix (ECM) defects of the superficial and middle layers of the lamina propria. The purpose of this study was to evaluate the biocompatibility of Carbylan GSX in a previously established immortalized human vocal fold fibroblast (hVFF) cell line prior to human clinical trials. Immortalized hVFF proliferation, viability, apoptosis and transcript analysis for both ECM constituents and inflammatory markers were measured for two-dimensional and three-dimensional culture conditions. There were no significant differences in morphology, cell marker protein expression, proliferation, viability and apoptosis of hVFF cultured with Carbylan GSX compared to Matrigel, a commercial 3D control, after one week. Gene expression levels for fibromodulin, TGF-β1, and TNF-α were similar between Carbylan GSX and Matrigel. Fibronectin, hyaluronidase 1 and COX2 expression levels were induced by Carbylan GSX; whereas IL6, IL8. COL1 and hyaluronic acid synthase 3 expression levels were decreased by Carbylan GSX. This investigation demonstrates that Carbylan GSX may serve as a natural biomaterial for tissue engineering of human vocal folds. PMID:20109588

  18. Efficient gaseous toluene photoconversion on graphene-titanium dioxide nanocomposites with dominate exposed {001} facets.

    PubMed

    Shang, Qianqian; Tan, Xin; Yu, Tao; Zhang, Zhiyang; Zou, Yunling; Wang, Siyu

    2015-10-01

    A series of GnTiO2 {001} nanocomposites (GTN) with dominate exposed {001} facets has been synthesized by various dosage of graphite oxide (GO) and hydrofluoric acid (HF) during a facile solvothermal process successfully. The photocatalytic degradation efficiency (PDE) of the optimal sample reached up to 98.7% for liquids methyl orange and up to 78.6% for gaseous toluene under the UV-light irradiation for 30 min, which is much higher than P25. The effects mechanism of HF and GO on the percentage of {001} facets exposed and the crystal morphology are investigated by XRD, SEM, TEM, UV-Vis, XPS and BET measurement, particularly. Cyclic voltammograms (CV) and electrochemical impedance spectroscopy (EIS) were used to explore the electron transfer mechanisms of GnTiO2 {001} nanocomposites. These results reveal the enhanced photocatalytic properties attribute to the excellent electron transport of Gn and highly reactive {001} facets can facilitate the separation of photo-generated charge carriers. Moreover, Gn can extend the absorption range of light and improve the adsorptivity of pollutant molecules.

  19. Aldehyde dehydrogenase 2 in cardiac protection: a new therapeutic target?

    PubMed Central

    Budas, Grant R; Disatnik, Marie- Hélène; Mochly-Rosen, Daria

    2010-01-01

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is emerging as a key enzyme involved in cytoprotection in the heart. ALDH2 mediates both the detoxification of reactive aldehydes such as acetaldehyde and 4-hydroxy-2-nonenal (4-HNE) and the bioactivation of nitroglycerin (GTN) to nitric oxide (NO). In addition, chronic nitrate treatment results in ALDH2 inhibition and contributes to nitrate tolerance. Our lab recently identified ALDH2 to be a key mediator of endogenous cytoprotection. We reported that ALDH2 is phosphorylated and activated by the survival kinase protein kinase C epsilon (PKCε) and found a strong inverse correlation between ALDH2 activity and infarct size. We also identified a small molecule ALDH2 activator (Alda-1) which reduces myocardial infarct size induced by ischemia/reperfusion in vivo. In this review, we discuss evidence that ALDH2 is a key mediator of endogenous survival signaling in the heart, suggest possible cardioprotective mechanisms mediated by ALDH2, and discuss potential clinical implications of these findings. PMID:20005475

  20. Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

    PubMed Central

    Mendonça, Vitor R. R.; Luz, Nívea F.; Santos, Nadja J. G.; Borges, Valéria M.; Gonçalves, Marilda S.; Andrade, Bruno B.

    2012-01-01

    Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria. PMID:22290142

  1. Towards Industrial Application of Damage Models for Sheet Metal Forming

    NASA Astrophysics Data System (ADS)

    Doig, M.; Roll, K.

    2011-05-01

    Due to global warming and financial situation the demand to reduce the CO2-emission and the production costs leads to the permanent development of new materials. In the automotive industry the occupant safety is an additional condition. Bringing these arguments together the preferable approach for lightweight design of car components, especially for body-in-white, is the use of modern steels. Such steel grades, also called advanced high strength steels (AHSS), exhibit a high strength as well as a high formability. Not only their material behavior but also the damage behavior of AHSS is different compared to the performances of standard steels. Conventional methods for the damage prediction in the industry like the forming limit curve (FLC) are not reliable for AHSS. Physically based damage models are often used in crash and bulk forming simulations. The still open question is the industrial application of these models for sheet metal forming. This paper evaluates the Gurson-Tvergaard-Needleman (GTN) model and the model of Lemaitre within commercial codes with a goal of industrial application.

  2. Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria.

    PubMed

    Mendonça, Vitor R R; Luz, Nívea F; Santos, Nadja J G; Borges, Valéria M; Gonçalves, Marilda S; Andrade, Bruno B; Barral-Netto, Manoel

    2012-04-01

    Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.

  3. A Study On Critical Thinning In Thin-walled Tube Bending Of Al-Alloy 5052O Via Coupled Ductile Fracture Criteria

    SciTech Connect

    Li Heng; Yang He; Zhan Mei

    2010-06-15

    Thin-walled tube bending(TWTB) method of Al-alloy tube has attracted wide applications in aerospace, aviation and automobile,etc. While, under in-plane double tensile stress states at the extrados of bending tube, the over-thinning induced ductile fracture is one dominant defect in Al-alloy tube bending. The main objective of this study is to predict the critical wall-thinning of Al-alloy tube bending by coupling two ductile fracture criteria(DFCs) into FE simulation. The DFCs include Continuum Damage Mechanics(CDM)-based model and GTN porous model. Through the uniaxial tensile test of the curved specimen, the basic material properties of the Al-alloy 5052O tube is obtained; via the inverse problem solution, the damage parameters of both the two fracture criteria are interatively determined. Thus the application study of the above DFCs in the TWTB is performed, and the more reasonable one is selected to obtain the critical thinning of Al-alloy tube in bending. The virtual damage initiation and evolution (when and where the ductile fracture occurs) in TWTB are investigated, and the fracture mechanisms of the voided Al-alloy tube in tube bending are consequently discussed.

  4. Characterization of neutron flux spectra in irradiation sites of MNSR reactor using the Westcott-formalism for the k0 neutron activation analysis method.

    PubMed

    Akaho, E H K; Nyarko, B J B

    2002-08-01

    For the general applicability of the k0-NAA method to deal with "non-l/v" (n,gamma) reaction nuclides, the modified spectral index r(alpha) square root (Tn/T0) and g(Tn) factor for monitoring neutron temperature Tn for the inner and outer irradiation sites of the Ghana MNSR reactor (GHARR-1) were measured using the Cd-ratio method. Using the measured Cd ratio for lutetium and the modified spectral index, the reduced resonance integral of lutetium s0,Lu was also calculated. The computed result of 1.64 was in good agreement with the reported value of 1.67. Based on the assumption that the definitions of reaction rates in the Westcott-formalism and in Nisle's unified formulation are equal, a theoretical verification of the accuracy of the measured modified spectral indices for our data and those reported in the literature for other research reactors was carried out. Employing 197Au, 96Zr and 94Zr as "1/v" monitors, the theoretical values which depend on the choice of the monitor, followed the trend for measured values of the sub- to epi-cadmium flux ratio f for nine irradiation sites of four different research reactors. The computed and experimental modified spectral indices for the different flux ratios associated with irradiation sites within the range 18.8-152 fitted well to a simple exponential relationship. Calculated and measured data are in good agreement when appropriate correction factors are used.

  5. A novel antiamoebic agent against Acanthamoeba sp. - A causative agent for eye keratitis infection

    NASA Astrophysics Data System (ADS)

    Kusrini, Eny; Hashim, Fatimah; Azmi, Wan Nor Nadhirah Wan Noor; Amin, Nakisah Mat; Estuningtyas, Ari

    2016-01-01

    The terbium trinitrate.trihydrate.18-crown ether-6, Tb(NO3)3(OH2)3.(18C6) complex has been characterized by elemental analysis, photoluminescence and single X-ray diffraction. The IC50 values were determined based on MTT assay while light and fluorescence microscopy imaging were employed to evaluate the cellular morphological changes. Alkaline comet assay was performed to analyze the DNA damage. The photoluminescence spectrum of the Tb complex excited at 325 nm displayed seven luminescence peaks corresponding to the 5D4 → 7F0, 1, 2, 3, 4, 5, 6 transitions. The cytotoxicity and genotoxicity studies indicated that the Tb(NO3)3(OH2)3.(18C6) complex and its salt form as well as the 18C6 molecule have excellent anti-amoebic activity with very low IC50 values are 7, 2.6 and 1.2 μg/mL, respectively, with significant decrease (p < 0.05) in Acanthamoeba viability when the concentration was increased from 0 to 30 μg/mL. The mode of cell death in Acanthamoeba cells following treatment with the Tb complex was apoptosis. This is in contrast to the Tb(NO3)3.6H2O salt- and 18C6 molecule-treated Acanthamoeba, which exhibited necrotic type cells. The percentage of DNA damage following treatment with all the compounds at the IC25 values showed high percentage of type 1 with the % nuclei damage are 14.15 ± 2.4; 46.00 ± 4.2; 36.36 ± 2.4; 45.16 ± 0.6%, respectively for untreated, treated with Tb complex, Tb salt and 18C6 molecule. The work features promising potential of Tb(NO3)3(OH2)3.(18C6) complex as anti-amoebic agent, representing a therapeutic option for Acanthamoeba keratitis infection.

  6. A novel antiamoebic agent against Acanthamoeba sp.--A causative agent for eye keratitis infection.

    PubMed

    Kusrini, Eny; Hashim, Fatimah; Azmi, Wan Nor Nadhirah Wan Noor; Amin, Nakisah Mat; Estuningtyas, Ari

    2016-01-15

    The terbium trinitrate.trihydrate.18-crown ether-6, Tb(NO3)3(OH2)3.(18C6) complex has been characterized by elemental analysis, photoluminescence and single X-ray diffraction. The IC50 values were determined based on MTT assay while light and fluorescence microscopy imaging were employed to evaluate the cellular morphological changes. Alkaline comet assay was performed to analyze the DNA damage. The photoluminescence spectrum of the Tb complex excited at 325 nm displayed seven luminescence peaks corresponding to the (5)D4→(7)F(0, 1, 2, 3, 4, 5, 6) transitions. The cytotoxicity and genotoxicity studies indicated that the Tb(NO3)3(OH2)3.(18C6) complex and its salt form as well as the 18C6 molecule have excellent anti-amoebic activity with very low IC50 values are 7, 2.6 and 1.2 μg/mL, respectively, with significant decrease (p<0.05) in Acanthamoeba viability when the concentration was increased from 0 to 30 μg/mL. The mode of cell death in Acanthamoeba cells following treatment with the Tb complex was apoptosis. This is in contrast to the Tb(NO3)3.6H2O salt- and 18C6 molecule-treated Acanthamoeba, which exhibited necrotic type cells. The percentage of DNA damage following treatment with all the compounds at the IC25 values showed high percentage of type 1 with the % nuclei damage are 14.15±2.4; 46.00±4.2; 36.36±2.4; 45.16±0.6%, respectively for untreated, treated with Tb complex, Tb salt and 18C6 molecule. The work features promising potential of Tb(NO3)3(OH2)3.(18C6) complex as anti-amoebic agent, representing a therapeutic option for Acanthamoeba keratitis infection.

  7. Synergistic effect of high and low molecular weight molecules in the foamability and foam stability of sparkling wines.

    PubMed

    Coelho, Elisabete; Reis, Ana; Domingues, M Rosário M; Rocha, Sílvia M; Coimbra, Manuel A

    2011-04-13

    The foam of sparkling wines is a key parameter of their quality. However, the compounds that are directly involved in foam formation and stabilization are not yet completely established. In this work, seven sparkling wines were produced in Bairrada appellation (Portugal) under different conditions and their foaming properties evaluated using a Mosalux-based device. Fractionation of the sparkling wines into four independent fractions, (1) high molecular weight material, with molecular weight higher than 12 kDa (HMW), (2) hydrophilic material with molecular weigh between 1 and 12 kDa (AqIMW), (3) hydrophobic material with molecular weigh between 1 and 12 kDa (MeIMW), and (4) hydrophobic material with a molecular weight lower than 1 kDa (MeLMW), allowed the observation that the wines presenting the lower foam stability were those that presented lower amounts of the MeLMW fraction. The fraction that presented the best foam stability was HMW. When HMW is combined with MeLMW fraction, the foam stability largely increased. This increase was even larger, approaching the foam stability of the sparkling wine, when HMW was combined with the less hydrophobic subfraction of MeLMW (fraction 3). Electrospray tandem mass spectrometry (ESI-MS/MS) of fraction 3 allowed the assignment of polyethylene glycol oligomers (n = 5-11) and diethylene glycol 8-hydroxytridecanoate glyceryl acetate. To observe if these molecules occur in sparkling wine foam, the MeLMW was recovered directly from the sparkling wine foam and was also analyzed by ESI-MS/MS. The presence of monoacylglycerols of palmitic and stearic acids, as well as four glycerylethylene glycol fatty acid derivatives, was observed. These surface active compounds are preferentially partitioned by the sparkling wine foam rather than the liquid phase, allowing the inference of their role as key components in the promotion and stabilization of sparkling wine foam.

  8. Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

    PubMed Central

    Jin, Xin; Zhang, Zhen-hai; Sun, E; Tan, Xiao-bin; Li, Song-lin; Cheng, Xu-dong; You, Ming; Jia, Xiao-bin

    2013-01-01

    Background 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 (AUC)0–∞] and PPD-cubosome containing piperine (AUC0–∞) compared to that of raw PPD (AUC0–∞) were 166% and 248%, respectively. Conclusion The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450. PMID:23426652

  9. Organization of genes required for gellan polysaccharide biosynthesis in Sphingomonas elodea ATCC 31461.

    PubMed

    Harding, Nancy E; Patel, Yamini N; Coleman, Russell J

    2004-02-01

    Sphingomonas elodea ATCC 31461 produces gellan, a capsular polysaccharide that is useful as a gelling agent for food and microbiological media. Complementation of nonmucoid S. elodea mutants with a gene library resulted in identification of genes essential for gellan biosynthesis. A cluster of 18 genes spanning 21 kb was isolated. These 18 genes are homologous to genes for synthesis of sphingan polysaccharide S-88 from Sphingomonas sp. ATCC 31554, with predicted amino acid identities varying from 61% to 98%. Both polysaccharides have the same tetrasaccharide repeat unit, comprised of [-->4)-alpha- l-rhamnose-(1-->3)-beta- d-glucose-(1-->4)-beta- d-glucuronic acid-(1-->4)-beta- d-glucose-(1-->]. Polysaccharide S-88, however, has mannose or rhamnose in the fourth position and has a rhamnosyl side chain, while gellan has no sugar side chain but is modified by glyceryl and acetyl substituents. Genes for synthesis of the precursor dTDP- l-rhamnose were highly conserved. The least conserved genes in this cluster encode putative glycosyl transferases III and IV and a gene of unknown function, gelF. Three genes ( gelI, gelM, and gelN) affected the amount and rheology of gellan produced. Four additional genes present in the S-88 sphingan biosynthetic gene cluster did not have homologs in the gene cluster for gellan biosynthesis. Three of these gene homologs, gelR, gelS, and gelG, were found in an operon unlinked to the main gellan biosynthetic gene cluster. In a third region, a gene possibly involved in positive regulation of gellan biosynthesis was identified.

  10. Effects of lubricants on binary direct compression mixtures.

    PubMed

    Uğurlu, T; Halaçoğlu, M D; Türkoğlu, M

    2010-04-01

    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.

  11. Hexagonal boron nitride as a tablet lubricant and a comparison with conventional lubricants.

    PubMed

    Uğurlu, Timuçin; Turkoğlu, Murat

    2008-04-02

    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.

  12. Antifungal activity of Zataria multiflora essential oil-loaded solid lipid nanoparticles in-vitro condition

    PubMed Central

    Nasseri, Mahboobeh; Golmohammadzadeh, Shiva; Arouiee, Hossein; Jaafari, Mahmoud Reza; Neamati, Hossein

    2016-01-01

    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. PMID:27917280

  13. Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil.

    PubMed

    Rajinikanth, Paruvathanahalli Siddalingam; Chellian, Jestin

    The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol(®) ATO 5 (glyceryl palmitostearate) and Labrasol(®) were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol(®) HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol(®) 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm(2)/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm(2)/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm(2)) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm(2)) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

  14. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    PubMed

    Zeng, Xiangfang; Sunkara, Lakshmi T; Jiang, Weiyu; Bible, Megan; Carter, Scott; Ma, Xi; Qiao, Shiyan; Zhang, Guolong

    2013-01-01

    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.

  15. Semiconductor particles in bilayer lipid membranes. Formation, characterization, and photoelectrochemistry

    SciTech Connect

    Zhao, X.K.; Baral, S.B.; Rolandi, R.; Fendler, J.H.

    1988-02-17

    Bilayer lipid membranes (BLMs) have been formed from bovine brain phosphatidylserine (PS), glyceryl monooleate (GMO), and a ploymerizable surfactant, (n-C/sub 15/H/sub 31/CO/sub 2/(CH/sub 2/))/sub 2/N/sup +/(CH/sub 3/)CH/sub 2/C/sub 6/H/sub 4/CH==CH/sub 2/Cl/sup -/(STYRS). These BLMs were then used to provide matrices for the in situ generation of microcrystalline CdS, CuS, Cu/sub 2/S, PbS, ZnS, HgS, and In/sub 2/S/sub 3/. Semiconductors were formed by injecting appropriate metal ion precursors and H/sub 2/S into the bathing solutions on opposite sides of the BLM. Their presence was established by voltage-dependent capacitance measurements, absorption spectroscopy, and optical microscopy. Subsequent to the injection of H/sub 2/S, the first observable change was the appearance of fairly uniform white dots on the black film. These dots rapidly moved around and grew in size, forming islands that then merged with themselves and with a second generation of dots, which ultimately led to a continuous film that continued to grow in thickness. Film formation and growth were monitored by simultaneous optical thickness and capacitance measurements. These data were treated in terms of an equivalent R-C circuit and allowed for the assessment of the semiconductor penetration depth into the BLM. This value for a GMO-BLM-supported In/sub 2/S/sub 3/ film was determined to be 24 A. Bandgap excitation, by nanosecond-pulsed or continuous illumination of the BLM-supported semiconductor film, led to observable photoelectric effects. Visible light (lambda > 350 nm) excitation into STYRS-BLM-supported CdS led to polymerization of the styrene moiety of STYRS. BLM-supported semiconductors remained stable for days.

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

    PubMed

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

    2016-08-01

    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 < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate 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.

  17. A "current contact news" follow-up: controversial subjects and those resulting in litigation.

    PubMed

    Fisher, A A

    1993-11-01

    In May 1993, the US Food and Drug Administration (FDA) granted product approval for the first female condom made of polyurethane. It provides some protection against sexually transmitted diseases (STDs), but the data are limited on the effectiveness of the Reality Vaginal Pouch against STDs. Female condom users have a relatively high pregnancy rate. FDA requires the label for Reality to stress that latex condoms for men are most effective against STDs and HIV/AIDS. Men who are sensitive to rubber can use condoms made of sheep intestine or cecum (brand names: Fourex and Lambskin). These nonrubber male condoms prevent pregnancy, but do not prevent HIV transmission. A specialist in contact dermatitis suggests that rubber sensitive men use a nonrubber condom directly over the penis and then cover that condom with a rubber condom to protect against HIV transmission. A nonlatex thermoplastic elastomer has been used to make male condoms since the early 1990s, but FDA has yet to approve it. A recent article suggests that a thermoplastic elastomer may be the only choice for rubber sensitive males. FDA approval will increase the availability of a nonlatex thermoplastic elastomer condom. The contact dermatitis specialist reviews and follows up on other articles he has written over the last 20 years. Topics include ethylene oxide burns in hospitalized patients, paraben paradox, benzocaine as a contaminant in sunscreens containing glyceryl PABA, sensitivity to nickel, misuse of a patch test to detect hypersensitivity to mercury amalgam dental fillings, permanent destruction of the fingernails due to an allergic reaction to an acrylic nail preparation, and dermatitis due to visual display units.

  18. Direct micellar systems as a tool to improve the efficiency of aromatic substrate conversion for fine chemicals production.

    PubMed

    Berti, D; Randazzo, D; Briganti, F; Baglioni, P; Scozzafava, A; Di Gennaro, P; Galli, E; Bestetti, G

    2000-04-01

    Whole-cell bioconversion of naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene by Escherichia coli JM109(pPS1778) recombinant strain, carrying naphthalene dioxygenase and regulatory genes cloned from Pseudomonas fluorescens N3, in direct micellar systems is optimized as an example of fine chemicals bioproduction from scarcely water-soluble substrates. The oxygen insertion into the aromatic substrate, which stops at the enantiomerically pure cis dihydroxylated product, is performed in direct microemulsion systems, where a non-ionic surfactant stabilizes naphthalene containing oil droplets in an aqueous medium. These media provide an increased substrate solubility so that a homogeneous reaction can be carried out, while not affecting bacteria viability and performances. The influence of the chemical nature of the oil is investigated. The phase behavior of the direct microemulsion system was monitored for three different oils as a function their volume fraction and characterized through light scattering. The addition of isopropyl palmitate, oleic acid, or glyceryl trioleate, 0.6-1.2% v/v to the micellar systems, led to an increase of the substrate concentration in the solution and particularly its bioavailability, allowing faster catalytic conversions. All these systems resulted in being suitable for catalytic conversions of aromatic compounds. Although the nature of the oil does have a deep effect on the phase behavior of the micellar systems, in the present investigation no differences in the yields and in the rates of product formation of the enzymatic system were observed on changing the oil, thus showing that in this case the substrate concentration or bioavailability is not the rate-limiting step.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24372651

  20. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration.

    PubMed

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Boyd, Ben J

    2011-07-30

    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 (p<0.05) in oral bioavailability (F%=21%) compared to a CZ suspension (9%) and oleic acid emulsion (12%). Analysis of the nanostructured 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.