Science.gov

Sample records for glyceryl trinitrate gtn

  1. Biotransformation of glyceryl trinitrate (GTN) in isolated bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV)

    SciTech Connect

    Not Available

    1986-03-01

    A proposed mechanism of GTN-induced vasodilation requires biotransformation of GTN to glyceryl dinitrate (GDN). They have previously shown that GTN is metabolized to GDN during relaxation of isolated rabbit aorta. The authors have extended this study to include BPA and BPV and to determine if their sensitivity to GTN correlates with their ability to metabolize GTN. Strips of BPA and BPV were contracted submaximally with KCl and then incubated with 0.5 ..mu..M /sup 14/C-GTN for 2 min. GTN-induced relaxation of these vessels was monitored and tissue GTN and metabolite concentrations were measured. Data are presented which support the above hypothesis that GTN biotransformation and relaxation occur together in vascular smooth muscle; however, there appear to be factors other than extent of GTN biotransformation that account for the difference in sensitivity to GTN of the artery and vein.

  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. Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

    SciTech Connect

    Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.; Bennett, B.M.; Nakatsu, K.; Marks, G.S.

    1986-05-01

    This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM (/sup 14/C)GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentration was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM (/sup 14/C)GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST

  4. The stability of glyceryl trinitrate tablets during patient use.

    PubMed

    Marty, J; Shaw, J; Hunt, D

    1983-04-01

    The stability of glyceryl trinitrate (GTN) tablets stored in ways commonly used by patients was investigated to enable pharmacists and physicians to give better advice about tablet storage. Analysis of 43 samples of tablets collected from hospital patients showed that the GTN content of these samples differed significantly from that of fresh tablets. Tablets kept in the manufacturer's bottle contained significantly more GTN than those transferred to other airtight vials (p less than 0.05) or pill boxes (p less than 0.005). The content of GTN was also significantly lower in tablets stored in pill boxes compared with other vials (p less than 0.01). Similar trends were found when tablets were stored in glass or plastic vials, pill boxes or were left exposed to air in the laboratory. These results emphasize that the best way to store GTN tablets is in the manufacturer's container. However, since many patients find that this bottle is awkward and inconvenient, a suitable alternative would be to carry a few tablets in a small airtight container (preferably glass). The unused tablets should be discarded every two weeks and nothing else should be added to the container. The use of pill boxes should be strongly discouraged. PMID:6412672

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

    PubMed

    Haebisch, E M

    1995-01-01

    In order to find an explanation for individual reactions to transdermal glyceryl trinitrate (GTN) we studied the skin temperature and hemodynamic reactions in 63 healthy persons. The data were obtained before and after the application of GTN and Glycerin (GL) placebo patches, during one hour. The skin temperature was measured on both forearms, the local (left sided) and systemic (right sided) reaction on GTN was related to the skin fold and the calculated body fat content. The bilateral rise of skin temperature and its duration was higher and longer in obese than in lean persons mainly in obese women. The UV induced thermo and the later photothermoreaction (Erythema) was reduced on the left forearm after the application of GTN and GL patches. The observed hemodynamic GTN effect confirmed known postural reactions, such as decreased arterial pressure (delta mAP = -2.9%), increased heart rate (delta HR = +7.4%) and QTc prolongation (delta QTc = +4.9%) in upright position. An adverse drug effect with increased mean blood pressure (delta mAP = +12%) and increased heart rate (delta HR = +10.4%) mainly in supine position was observed in 11% of the participants, but only in men. Such a reaction was already described by Murell, 1879. Individual GTN effects were analyzed and related to habits and family history. In male smokers and in persons with hypertensive and diabetic close relatives, the hypotensive GTN effect was accentuated in supine position. In the upright position the group with hypertensives in the family presented a moderate hypotensive reaction without secondary tachycardia and the smokers presented only a slightly increased heart rate. Our observations suggest that individual reactions to transdermal glyceryl trinitrate (GTN) with its active component nitric oxide (NO) depends on physiological conditions, related to endogenous vasoactive substances, mainly the interaction with EDRF (the endogenous NO) and the activity of the Renin-Angiotensin System. PMID

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

    PubMed

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

    2012-05-15

    Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species. PMID:22465477

  7. Analysis of Responses to Glyceryl Trinitrate and Sodium Nitrite in the Intact Chest Rat

    PubMed Central

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

    2012-01-01

    Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000 fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species. PMID:22465477

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

    PubMed

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

    2010-09-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat. PMID:20543077

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

    PubMed Central

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

    2010-01-01

    It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was ∼1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat. PMID:20543077

  10. 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

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

    PubMed

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

    2015-03-30

    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

  12. 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

  13. Cardioprotective effects of glyceryl trinitrate: beyond vascular nitrate tolerance.

    PubMed

    Csont, Tamás; Ferdinandy, Péter

    2005-01-01

    Organic nitrates have been used for the treatment of ischemic heart diseases for more than 100 years and these drugs are still amongst the most frequently prescribed and applied drugs worldwide. Development of tolerance against the hemodynamic effects of nitrates during sustained therapy, however, limits their clinical application. Moreover, recent clinical studies have suggested that long-term nitrate treatment does not improve or may even worsen cardiovascular mortality, possibly due to the development of vascular nitrate tolerance. In agreement with these clinical findings, nitrate tolerance has been shown to increase superoxide and peroxynitrite production leading to vascular dysfunction. Nevertheless, nitrates exert a direct myocardial anti-ischemic effect that is independent from their vascular actions. The direct myocardial effect of glyceryl trinitrate (GTN) has been shown to be preserved even in the state of vascular nitrate tolerance. Moreover, no oxidative stress was observed in hearts isolated from rats with vascular nitrate tolerance, while increased systemic peroxynitrite formation was detected in the plasma in the same animals. The different effects of nitrates on the heart and vasculature are not well characterized; however, tissue specific differences in the metabolism and cellular signaling of nitrates might be a plausible explanation. These data suggest that sustained nitrate treatment increases oxidative stress in the extracardiac vasculature, thereby promoting the development of vascular nitrate tolerance. However, the direct myocardial anti-ischemic effect of nitrates seems to be preserved beyond the development of vascular nitrate tolerance. These new findings may open new perspectives in the clinical use of organic nitrates and suggest that the development of either cardioselective nitrates or nitrate-antioxidant hybrid drugs may replace classical nitrates in the therapy of ischemic heart disease. PMID:15626455

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

    PubMed

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P < .015; 95% confidence intervals 0.25-0.77). There was also an increase in the HOMA-IR index; on visit 1, the median HOMA-IR (interquartile range) was 5.2 (3.9) versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans. PMID:23230283

  15. Sublingual glyceryl trinitrate and the peripheral thermal responses in normal and cold-sensitive individuals.

    PubMed

    Hope, Katrina; Eglin, Clare; Golden, Frank; Tipton, Mike

    2014-01-01

    Non-freezing cold injury (NFCI) is a prevalent, but largely undiagnosed and poorly understood syndrome afflicting many who, as part of their work or leisure, expose their extremities to cold temperatures. The long term sequelae of NFCI are hyperhidrosis, cold-sensitivity and pain; these can last a lifetime. We tested the hypothesis that, in comparison with a placebo, sublingual glyceryl trinitrate (GTN) would increase the peripheral microcirculation during and after a mild cold challenge of individuals who had not been diagnosed with NFCI, but were cold-sensitive. Naive participants were categorised into two cohort groups: control (n=7) or cold-sensitive (n=6). All participants undertook a standardised two minute cold exposure of their right foot while toe skin temperature (Tsk; infra-red thermograms) and blood flow (toe pad laser Doppler) were measured. GTN increased the rate of rewarming and absolute Tsk of the coldest toe after the cold challenge in cold-sensitive individuals. GTN also increased the blood flow in the great toe during rewarming in some cold-sensitive individuals. We accept our hypothesis and suggest that the impairment in the vasodilatory response seen in individuals with cold-sensitivity can be overcome by the use of GTN, an endothelial-independent NO donor, and thereby improve the rewarming of cooled peripheral tissues. PMID:24280630

  16. Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility

    PubMed Central

    Greaves, R; Miller, J; O'Donnell, L; McLean, A; Farthing, M

    1998-01-01

    Background—Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined.
Aims—To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, crossover, placebo controlled design.
Methods—Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 µg buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 µg buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal. 
Results—Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p=0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p=0.016).
Conclusions—This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo. 

 Keywords: gall bladder motility; nitric oxide; glyceryl trinitrate PMID:9577350

  17. [Effects of nitrogen oxide donor glyceryl trinitrate on pressure pain threshold in humans].

    PubMed

    Thomsen, L L; Brennum, J; Iversen, H K; Olesen, J

    1997-07-21

    The purpose of the present study was to examine the effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) on nociceptive thresholds in man. On two different study days twelve healthy subjects received a stair case infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min 20 min each dose) or placebo in a randomized double-blind cross-over design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection- and tolerance thresholds were determined by pressure algometry in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue). Relative to placebo the three higher GTN doses induced a decrease in both detection- and tolerance-thresholds in the temporal region with interposed myofascial tissue. No such changes were observed in the two other stimulated regions. These results could reflect central facilitation of nociception by NO. However, convergence of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO may provide a more likely explanation. PMID:9245041

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

    PubMed

    Thomsen, L L; Brennum, J; Iversen, H K; Olesen, J

    1996-05-01

    Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate (GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive thresholds in man. On two different study days separated by at least a week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min, 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection and tolerance thresholds were determined by pressure algometry (Somomedic AB, Sweden) in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue). Relative to placebo, the three higher GTN doses induced a decrease in both detection and tolerance thresholds in the temporal region with interposed myofascial tissue (p = 0.003 detection and p = 0.002 tolerance thresholds, Friedman). No such changes were observed in the other two stimulated regions. These results could reflect central facilitation of nociception by NO. However, we regard convergence of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely explanation of our findings. PMID:8734768

  19. The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man.

    PubMed

    White, R P; Deane, C; Hindley, C; Bloomfield, P M; Cunningham, V J; Vallance, P; Brooks, D J; Markus, H S

    2000-09-01

    Despite their potential use as cerebral vasodilatory agents there are few studies of the effect of nitric oxide (NO) donors on the cerebral circulation in non-anaesthetised man. We determined the effect of the NO donor glyceryl trinitrate (GTN) at clinically relevant doses on global and regional cerebral blood flow (CBF) in healthy non-anaesthetised volunteers, using H(2)(15)O PET, ultrasonic colour velocity flow imaging of carotid artery flow, and transcranial Doppler (TCD) of middle cerebral artery velocities (MCAv). Three rates of GTN infusion (0.1, 0.4, 1.0 microg/kg/min) were used. There was no significant change in common or internal carotid artery flow following GTN administration although a dose dependent fall in MCAv post GTN was observed. There was no significant change in either global or regional CBF following GTN. Thus intravenous GTN at therapeutic doses in awake humans does not alter global or regional CBF. However it does produce basal cerebral artery vasodilatation as evidenced by a fall in MCAv in the absence of a change in internal carotid artery flow. PMID:11018245

  20. 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

  1. The Effects of Glyceryl Trinitrate Patch on the Treatment of Preterm Labor: A Single-blind Randomized Clinical Trial

    PubMed Central

    Nankali, Anisodowleh; Jamshidi, Parnian Kord; Rezaei, Mansour

    2014-01-01

    Background Preterm labor (PTL) is one of the main causes of neonatal mortality and morbidity. PTL leads to serious complications especially in the gestational age prior to 24-26 weeks. The aim of this study was to investigate the effect of glyceryl trinitrate (GTN) patch on the treatment and complications of PTL. Methods In this clinical trial, 84 singleton pregnant women with gestational age of 27-35 weeks were surveyed. PTL was clinically diagnosed and the patients were randomly divided into two groups who were treated with GTN or placebo for 48 hr. The consequences, complications and changes in some parameters in both groups were compared. Data were analyzed with chi square test, paired and unpaired t tests by SPSS software and p<0.05 was considered significant. Results No significant difference was observed between two groups in terms of successful tocolysis, receiving full dose of corticosteroids and the mean prolongation of the pregnancy. However, delivery times in patients who delivered during the hospitalization were 31±4.4 and 18.3±2.2 hr (p=0.01), respectively. Headache was more severe in control group (p=0.007). The systolic and mean arterial blood pressure decrease (p<0.001) and maternal heart rate increase (p=0.01) were significant in GTN group. The changes of vital signs were not significant in placebo group. Conclusion The effect of GTN in the treatment of PTL is similar to the placebo without any serious complication. However, GTN delays the delivery time in delivery during the primary hospitalization. Thus, further studies with larger sample size are needed to evaluate the exact effects of GTN on PTL. PMID:24918079

  2. Conversion of glyceryl trinitrate to nitric oxide in tolerant and non-tolerant smooth muscle and endothelial cells.

    PubMed Central

    Salvemini, D.; Pistelli, A.; Vane, J.

    1993-01-01

    1. Exposure of smooth muscle cells (SMC) to glyceryl trinitrate (GTN, 75-600 microM) for 30 min led to a concentration-dependent increase in nitrite (NO2-), one of the breakdown products of nitric oxide (NO). This was not affected by 30 min pretreatment of the cells with 0.5 mM of sulphobromophthalein (SBP) an inhibitor of glutathione-S-transferase (GST), by metyrapone or SKF-525A inhibitors of cytochrome P450. These experiments were confirmed by organ bath studies using rabbit aortic strips denuded of endothelium and contracted with phenylephrine. Thus, a 30 min incubation of the strips with 0.5 mM SPB, metyrapone or SKF-525A did not affect the relaxations in response to GTN (10(-10)-10(-6) M). 2. Potentiation of the anti-platelet effect of GTN (44 microM) by endothelial cells (EC, 40 x 10(3) cells) was not affected by prior incubation of EC with SBP, metyrapone or SKF-525A (all at 0.5 mM). 3. Potentiation of the antiplatelet activity of GTN (11-352 microM) by small numbers of SMC (24 x 10(3) cells) or EC (40 x 10(3) cells) treated with indomethacin (10 microM) was attenuated when the SMC or EC were treated in culture with a high concentration of GTN (600 microM) for 18 h beforehand (referred to as 'tolerant' cells). In addition, tolerant SMC produced far less NO2- than non-tolerant SMC. 4. Exposure of non-tolerant SMC or EC (10(5) cells) to GTN (200 microM) for 3 min increased (3-4 fold) the levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8381319

  3. 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. PMID:26745983

  4. Assay of glyceryl trinitrate, isosorbide dinitrate, and their metabolites in plasma by large-bore capillary column gas-liquid chromatography.

    PubMed

    Booth, B P; Bennett, B M; Brien, J F; Elliott, D A; Marks, G S; McCans, J L; Nakatsu, K

    1990-11-01

    Two large-bore capillary columns, one with dimethyl polysiloxane (HP-1) as the stationary phase and the other with phenyl (50 per cent) methyl (50 per cent) polysiloxane (DB-17), were used to develop gas-liquid chromatographic (GLC) assays for measuring isosorbide dinitrate (ISDN), glyceryl trinitrate (GTN), and their metabolites. ISDN, isosorbide-2-mononitrate (2-ISMN), and isosorbide-5-mononitrate (5-ISMN) in plasma, ranging in concentration from 1 to 300 nM, and GTN, glyceryl-1,2-dinitrate (1,2-GDN), and glyceryl-1,3-dinitrate (1,3-GDN), ranging in concentration from 3 to 60 nM in plasma, were analysed on both columns. GLC analysis yielded baseline resolution of the analytes. The method using the dimethyl polysiloxane column gave a lower limit of detectability for GTN of 0.75 nM (signal/noise (s/n) = 2), and the procedure using the phenyl-methyl column provided a lower limit of detectability for ISDN of 81 pM (s/n = 2). The large-bore column GLC procedures exhibited shorter retention times for both ISDN and GTN than those previously reported for capillary-column assays. The chromatographic resolution of analytes and column efficiency of the large-bore capillary columns were comparable to the results previously found using capillary-column GC. The assays for ISDN and GTN have been shown to be appropriate for pharmacokinetic studies in volunteers and patients. We determined that the HP-1 column is appropriate for the analysis of GTN and metabolites, and the DB-17 column is suitable for analysis of ISDN and its metabolites. We conclude that the use of large-bore capillary columns provides rapid and reliable GLC assays for organic nitrates. PMID:2125512

  5. Hemodynamic effect of avanafil and glyceryl trinitrate coadministration

    PubMed Central

    Swearingen, Dennis; Nehra, Ajay; Morelos, Susie; Peterson, Craig A

    2013-01-01

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

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

    PubMed

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

    2015-03-01

    Migraine headaches are considered to be associated with increased mitochondrial energy metabolism. Mitochondrial oxidative stress is also important in migraine headache pathophysiology although riboflavin and selenium (Se) induced a modulator role on mitochondrial oxidative stress in the brain. The current study aimed to determine the effects of Se with/without riboflavin on the microsomal membrane Ca(2+)-ATPase (MMCA), lipid peroxidation, antioxidant, and electroencephalography (EEG) values in glyceryl trinitrate (GTN)-induced brain injury rats. Thirty-two rats were randomly divided into four groups. The first group was used as the control, and the second group was the GTN group. Se and Se plus oral riboflavin were administered to rats constituting the third and fourth groups for 10 days prior to GTN administration. The second, third, and fourth groups received GTN to induce headache. Ten hours after the administration of GTN, the EEG records and brain cortex samples were obtained for all groups. Brain cortex microsomes were obtained from the brain samples. The brain and microsomal lipid peroxidation levels were higher in the GTN group compared to the control group, whereas they were decreased by selenium and selenium + riboflavin treatments. Vitamin A, vitamin C, vitamin E, and reduced glutathione (GSH) concentrations of the brain and MMCA, GSH and glutathione peroxidase values of microsomes were decreased by the GTN administration, although the values and β-carotene concentrations were increased by Se and Se + riboflavin treatments. There was no significant change in EEG records of the four groups. In conclusion, Se with/without riboflavin administration protected against GTN-induced brain oxidative toxicity by inhibiting free radicals and the modulation of MMCA activity and supporting the antioxidant redox system. PMID:25492827

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

    PubMed

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

    2015-04-01

    The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, β-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin. PMID:25425044

  8. A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate.

    PubMed

    Berndt, Georg; Grosser, Nina; Hoogstraate, Janet; Schröder, Henning

    2004-02-01

    4-(Nitrooxy)-butyl-(S)-2-(6-methoxy-2-naphthyl)-propanoate (AZD3582) is a cyclooxygenase (COX)-inhibiting nitric oxide donator (CINOD). It donates nitric oxide (NO) in biological systems through as yet unidentified mechanisms. cGMP, a marker of intracellularly generated NO, was increased up to 27-fold over basal levels by AZD3582 (1-30microM) in LLC-PK1 kidney epithelial cells. A 5h pretreatment with glyceryl tinitrate (GTN, 0.1-1microM) attenuated the cGMP response to a subsequent challenge with AZD3582 or GTN. Similarly, AZD3582 (10-30microM) pretreatment reduced the increase in cGMP on subsequent incubation with AZD3582 or GTN. In contrast, cGMP stimulation by SIN-1, which releases NO independently of enzymatic catalysis, remained unimpaired in cells pretreated with GTN or AZD3582. Our results demonstrate that AZD3582 decreases the sensitivity of the guanylyl cyclase/cGMP system to GTN and vice versa. This suggests that bioactivation pathways for organic nitrates, which involve enzymatic catalysis, may be responsible for NO donation from AZD3582. PMID:14757506

  9. Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation.

    PubMed

    van Wezel, H B; Bovill, J G; Koolen, J J; Patrick, M R; Fiolet, J W; van der Stroom, J G

    1986-09-01

    The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function. PMID:3092847

  10. Time-dependent inhibition by glyceryl trinitrate of platelet aggregation caused by U46619 (a thromboxane/endoperoxide receptor agonist).

    PubMed

    Kampf, G; Ritter, J M

    1994-07-01

    Glyceryl trinitrate is a weak inhibitor of platelet aggregation in vitro. Its effect on platelet aggregation in response to U46619 (a thromboxane/endoperoxide receptor agonist) was studied turbidometrically in platelet-rich plasma from healthy volunteers. The object was to determine whether inhibition was influenced by a period of preincubation between preparation of platelet-rich plasma and addition of glyceryl trinitrate. Incubation was performed at 37 degrees C and 22 degrees C. Samples were removed at intervals and transferred to an aggregometer cuvette at 37 degrees C. Glyceryl trinitrate (100 microM) or an equal volume of distilled water was added 5 min before U46619 (2 microM), and aggregation recorded as change in light transmission. Inhibition by glyceryl trinitrate was markedly time and temperature dependent, with a progressive increase in inhibitory potency between 120 and 300 min preincubation at 37 degrees C but not at 22 degrees C. The explanation of this is unknown but the effect was not influenced by lipopolysaccharide or by cycloheximide, so it does not appear to be due to exposure to endotoxin or to enzyme induction in vitro. PMID:7946941

  11. 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

  12. Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators.

    PubMed Central

    Fox, K M; Dargie, H J; Deanfield, J; Maseri, A

    1991-01-01

    OBJECTIVES--To investigate the efficacy of transdermal glyceryl trinitrate given continuously and with a nocturnal nitrate free period. DESIGN--Double blind placebo controlled study with two parallel limbs. SETTING--Multicentre trial. PATIENTS--52 patients randomised to receive either continuous treatment (23 patients) or intermittent treatment with an individually titrated dose (29 patients) for 14 days: both treatments were compared with placebo in a cross-over fashion. INTERVENTION--Continuous treatment with 10 mg per 24 hours of transdermal glyceryl trinitrate or intermittent transdermal glyceryl trinitrate titrated to give an arbitrary 10 mm Hg drop in systolic blood pressure (mean dose 18.2 mg) given over approximately 16 hours. MAIN OUTCOME MEASURE--Treadmill exercise stress testing and ambulatory monitoring of the ST segment after 14 days' treatment. RESULTS--After 14 days' intermittent treatment resting supine and standing systolic blood pressure fell by 7.5 mm Hg (95% confidence interval 2.7 to 12.2) and 9.0 mm Hg (95% CI 3.4 to 14.5) respectively (p less than 0.01); resting heart rate was unchanged. Mean heart rate at 1 mm ST segment depression rose by 11.9 beats/min (CI 1.1 to 23.7) (p less than 0.05), mean time to onset of angina increased by 59 seconds (CI 10.8 to 108) (p less than 0.05), and total exercise duration increased by 40 seconds (p less than 0.05). These changes were not seen after continuous treatment. The frequency of ischaemic episodes was not reduced with either regimen nor was the circadian distribution of these episodes altered, in particular nocturnal episodes did not increase during intermittent treatment. CONCLUSION--Tolerance to glyceryl trinitrate was avoided by the use of individually titrated doses administered with a nocturnal nitrate free period. There was no evidence of "rebound" on ambulatory monitoring during this treatment. PMID:1909152

  13. Lack of rebound during intermittent transdermal treatment with glyceryl trinitrate in patients with stable angina on background beta blocker.

    PubMed Central

    Holdright, D R; Katz, R J; Wright, C A; Sparrow, J L; Sullivan, A K; Cunningham, A D; Fox, K M

    1993-01-01

    OBJECTIVE--To assess whether intermittent transdermal treatment with glyceryl trinitrate causes clinically significant rebound in patients maintained on beta blockers for stable angina pectoris. DESIGN--Serial treadmill exercise testing in a double blind, randomised, placebo controlled cross over trial. Baseline exercise testing was performed at 0900 and 1100 at visit 1. Transdermal glyceryl trinitrate patches releasing 15 mg/24 h were applied at 2200 the evening before visits 2 and 3, and exercise testing was performed at 0900 the next morning. The patch was removed and replaced with either an identical patch or matching placebo and exercise tests were repeated two hours later. The alternative treatment was given at visit 3. SETTING--Tertiary referral centre. PATIENTS--14 patients with stable angina pectoris maintained on beta blocker treatment alone. MAIN OUTCOME MEASURES--Time to angina, 1 mm ST segment depression, and total time, together with heart rate, systolic blood pressure, and rate-pressure product. RESULTS--Active treatment improved treadmill performance at 0900 and 1100. Time to angina, time to 1 mm ST segment depression, and total time fell significantly on placebo compared with the 0900 exercise test on active treatment, but were not significantly different to the baseline exercise test either. CONCLUSIONS--Intermittent transdermal treatment with glyceryl trinitrate is not associated with the rebound phenomenon in patients maintained on beta blockers for stable angina pectoris. PMID:8096389

  14. Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.

    PubMed

    Schankin, Christoph J; Maniyar, Farooq H; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E; Blecha, Joseph; Murphy, Stephanie T; Hawkins, Randall A; Sprenger, Till; VanBrocklin, Henry F; Goadsby, Peter J

    2016-07-01

    SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. PMID:27234268

  15. Ictal lack of binding to brain parenchyma suggests integrity of the blood–brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine

    PubMed Central

    Schankin, Christoph J.; Maniyar, Farooq H.; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E.; Blecha, Joseph; Murphy, Stephanie T.; Hawkins, Randall A.; Sprenger, Till; VanBrocklin, Henry F.

    2016-01-01

    See Dreier (doi: 10.1093/aww112) for a scientific commentary on this article. For many decades a breakdown of the blood–brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood–brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand 11C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood–brain barrier penetration. At rest, there was binding of 11C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood–brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that 11C-dihydroergotamine is unable to cross the blood–brain barrier interictally or ictally demonstrating that the blood–brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. PMID:27234268

  16. 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

  17. 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

  18. 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

  19. The GTN-AAVSO Blazar Program

    NASA Astrophysics Data System (ADS)

    Cominsky, L. R.; Spear, G. G.; Graves, T.; Slater, G.; Price, A.

    2004-08-01

    The GLAST Telescope Network (GTN) is a collaboration among students, teachers, amateur astronomers, small college observatories, and professional astronomers who will obtain observations of base-line activity levels and follow-up observations for bright blazars, one of the key science objectives for NASA's Gamma-ray Large Area Space Telescope (GLAST) mission. A key partner in the GTN is the American Association of Variable Star Observers (AAVSO, a non-profit international scientific and educational organization that has considerable experience with handling, processing, and displaying large amounts of data and with coordinating observers from every corner of the globe. The GTN-AAVSO blazar program will recommend observing sequences, and provide advice and mentoring for observing techniques and data reduction. The program will archive magnitude estimates using the AAVSO database system and lightcurve generator, as well as CCD images of blazar fields. The program will also employ the online image archiving system developed by the GTN. Images of blazar fields will be available for subsequent analysis by contributors to the program, and by the GLAST science team for mission planning and follow-up studies. We will present examples of the AAVSO lightcurve generator, examples of the GTN image archive system, plus examples of the data we are currently accumulating. The GTN-AAVSO collaboration is partially funded by the NASA's GLAST Education and Public Outreach Program.

  20. The GTN-AAVSO Blazar Program

    NASA Astrophysics Data System (ADS)

    Spear, G. G.; Mattei, J. A.; Price, A.; Graves, T.; Borders, T.; Slater, G.; Cominsky, L. R.

    2002-12-01

    The GLAST Telescope Network (GTN) is a collaboration among observers and small observatories who will obtain observations of base-line activity levels and follow-up observations for bright blazars. These AGNs have their jets pointed directly toward us, and are one of the key science objectives for NASA's Gamma-ray Large Area Space Telescope (GLAST) mission. Funded by the GLAST Education and Public Outreach Program, the GTN consists of students, teachers, amateur astronomers, small college observatories, and professional astronomers. The American Association of Variable Star Observers (AAVSO) is a non-profit international scientific and educational organization of thousands of advanced amateur and professional astronomers interested in stars or star-like objects that change in brightness. With millions of variable star observations dating back more than 90 years, the AAVSO has unique experience with handling, processing, and displaying large amounts of data and with coordinating observers from every corner of the globe. The GTN-AAVSO blazar program will recommend observing programs, and provide advice and mentoring for observing techniques and data reduction. The program will archive magnitude estimates and measurements of blazars, as well as CCD images of blazar fields. The GTN-AAVSO program will employ the AAVSO database system and lightcurve generator (http://www.aavso.org/adata/curvegenerator.shtml) to archive magnitude estimates. The magnitudes will either be visual estimates or CCD measurements. Magnitudes are submitted online, and will be immediately available to the public for use in planning observing programs and estimating current activity levels. The GTN-AAVSO program will also employ the online image archiving system developed by the GTN. Images of blazar fields will be available for subsequent analysis by contributors to the program, and by the GLAST science team for mission planning and follow-up studies. We will present examples of the AAVSO

  1. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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. No. 555-43-1) is prepared...

  2. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Glyceryl monostearate. 184.1324 Section 184.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1324 Glyceryl monostearate....

  3. 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...

  4. 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)...

  5. 21 CFR 582.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Glyceryl monostearate. 582.1324 Section 582.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  6. 21 CFR 582.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Glyceryl monostearate. 582.1324 Section 582.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Purpose...

  7. 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... (C21H40O4, CAS Reg. No. 25496-72-4) and glyceryl esters of fatty acids present in commercial oleic acid....

  8. 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... (C21H40O4, CAS Reg. No. 25496-72-4) and glyceryl esters of fatty acids present in commercial oleic acid....

  9. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  10. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  11. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  12. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  13. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glyceryl monostearate. 184.1324 Section 184.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  14. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glyceryl monostearate. 184.1324 Section 184.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  15. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glyceryl monostearate. 184.1324 Section 184.1324 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS...

  16. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Glyceryl tristearate. 172.811 Section 172.811 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.811...

  17. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Glyceryl tristearate. 172.811 Section 172.811 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.811...

  18. 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... (C21H40O4, CAS Reg. No. 25496-72-4) and glyceryl esters of fatty acids present in commercial oleic acid....

  19. 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.

  20. Elderly, conscious patients have an accentuated hypotensive response to nitroglycerin.

    PubMed

    Cahalan, M K; Hashimoto, Y; Aizawa, K; Verotta, D; Ionescu, P; Balea, M; Eger, E I; Benet, L Z; Ehrenfeld, W K; Goldstone, J

    1992-10-01

    There is no adequate explanation for the highly variable response of systemic blood pressure to nitroglycerin (glyceryl trinitrate [GTN]). Aging produces cardiovascular changes that should alter the effects of GTN, but elderly patients usually have been excluded from studies of GTN. Accordingly, the authors compared the effects of GTN on systemic blood pressure in elderly and younger patients. Fifty-three patients, aged 49-87 (with 30 patients older than 70), were studied. Before elective vascular surgery, 14 patients received an infusion of placebo; 26, a constant infusion of GTN; and 13, a stepwise increasing infusion of GTN. After a standardized anesthetic induction and the start of surgery, the identical infusion protocols were repeated in each group. Data on GTN infusion rate, arterial blood pressure, and GTN concentrations versus time, age, and other potentially influencing variables were pooled for analysis. Before anesthesia and surgery, GTN more commonly caused excessive hypotension in patients older than 70 yr than in younger patients, but none of the patients had complications. A repeated-measures model analysis indicated that age significantly influenced the effects of GTN on blood pressure. That is, patients who are in their 70s who receive 0.5 micrograms.kg-1.min-1 of GTN are predicted to experience a twofold greater decrease in systolic arterial pressure (approximately 33 mmHg) than patients in their 50s. However, no apparent effect of age on intraoperative GTN responsiveness was discernible nor was a predictable relationship found between the preoperative and intraoperative responsiveness or between arterial concentrations of GTN and blood pressure or age. Therefore, the authors conclude that, in the absence of the effects of anesthesia and surgery, elderly patients have a more pronounced blood pressure response to GTN than younger patients. Furthermore, the authors conclude that preoperative blood pressure responsiveness to GTN is not a reliable

  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. 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

  3. 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). PMID:26796748

  4. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... § 172.852 Glyceryl-lacto esters of fatty acids. Glyceryl-lacto esters of fatty acids (the lactic acid... conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty acids conforming with § 172.862 and/or edible fats...

  5. 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.

  6. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  7. 21 CFR 178.3505 - Glyceryl tri-(12-acetoxy-stearate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  8. 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

  9. 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. PMID:27180439

  10. 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.

  11. 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.

  12. Vascular Bioactivation of Nitroglycerin by Aldehyde Dehydrogenase-2

    PubMed Central

    Lang, Barbara S.; Gorren, Antonius C. F.; Oberdorfer, Gustav; Wenzl, M. Verena; Furdui, Cristina M.; Poole, Leslie B.; Mayer, Bernd; Gruber, Karl

    2012-01-01

    Aldehyde dehydrogenase-2 (ALDH2) catalyzes the bioactivation of nitroglycerin (glyceryl trinitrate, GTN) in blood vessels, resulting in vasodilation by nitric oxide (NO) or a related species. Because the mechanism of this reaction is still unclear we determined the three-dimensional structures of wild-type (WT) ALDH2 and of a triple mutant of the protein that exhibits low denitration activity (E268Q/C301S/C303S) in complex with GTN. The structure of the triple mutant showed that GTN binds to the active site via polar contacts to the oxyanion hole and to residues 268 and 301 as well as by van der Waals interactions to hydrophobic residues of the catalytic pocket. The structure of the GTN-soaked wild-type protein revealed a thionitrate adduct to Cys-302 as the first reaction intermediate, which was also found by mass spectrometry (MS) experiments. In addition, the MS data identified sulfinic acid as the irreversibly inactivated enzyme species. Assuming that the structures of the triple mutant and wild-type ALDH2 reflect binding of GTN to the catalytic site and the first reaction step, respectively, superposition of the two structures indicates that denitration of GTN is initiated by nucleophilic attack of Cys-302 at one of the terminal nitrate groups, resulting in formation of the observed thionitrate intermediate and release of 1,2-glyceryl dinitrate. Our results shed light on the molecular mechanism of the GTN denitration reaction and provide useful information on the structural requirements for high affinity binding of organic nitrates to the catalytic site of ALDH2. PMID:22988236

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

    PubMed

    Johnson, W

    2001-01-01

    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

  14. 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

  15. Prostaglandin E2-Glyceryl Ester: In Vivo Evidence for a Distinct Pharmacological Identity from Intraocular Pressure Studies.

    PubMed

    Woodward, David F; Poloso, Neil J; Wang, Jenny W

    2016-08-01

    Prostaglandin E2 (PGE2)-2-glyceryl ester is a cyclo-oxygenase 2 product of the endocannabinoid 2-arachidonyl glycerol. It is claimed as pharmacologically novel, but this is complicated by rapid and irreversible isomerization to the 1(3) ester. For ocular studies, enzymatic hydrolysis of the ester moiety creates an additional complication. PG-glyceryl esters were stabilized to isomerization and hydrolysis by replacing the noncarbonyl O with NH, to form the serinolamide and propanediolamide as stable analogs of PG-2-glyceryl and PG-2-1(3) glyceryl esters, respectively. Intraocular pressure was measured in conscious dogs and conscious laser-induced ocular hypertensive monkeys. Pharmacological studies involved stable transfectants for each of the human recombinant prostanoid receptors and the isolated feline iris for prostamide activity. PGE2-serinolamide and PGE2- propanediolamide were essentially inactive at all receptors except the EP3 receptor (EC50, ∼500 nM). This obliged elucidation of EP3 receptor involvement in the intraocular pressure response to these PGE2-glycyerl ester analogs. Since the EP3 receptor agonists sulprostone and GR 63799 did not lower monkey intraocular pressure, a role for EP3 receptors in mediating the effects of PGE2-serinolamide and PGE2-propanediolamide is not indicated. PGE2-glyceryl ester (0.01% and 0.1%) substantially lowered intraocular pressure in monkeys. PGE2-propanediolamide was more efficacious than PGE2-serinolamide in lowering intraocular pressure in monkey eyes, but both appeared equieffective in dog eyes. PGE2-serinolamide dose-dependently (0.01- 0.1%) lowered intraocular pressure in both species, but PGF2 α-serinolamide was inactive. In conclusion, stable PGE2-glyceryl ester analogs lowered intraocular pressure. These findings are consistent with the presence of a PGE2-glyceryl ester-specific recognition site in the eye. PMID:27217589

  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. Water-developable resists based on glyceryl methacrylate for 193-nm lithography

    NASA Astrophysics Data System (ADS)

    Kim, Jin-Baek; Jang, Ji-Hyun; Choi, Jae-Hak; Lee, Kwan-Ku; Ko, Jong-Sung

    2004-05-01

    Novel water-developable negative resists were designed to induce both cross-linking and polarity change upon exposure and bake. The matrix polymers were synthesized by copolymerization of glyceryl methacrylate and methacrolein. The acid-catalyzed acetalization of the polymer induced cross-linking, polarity change, and increase in dry-etch resistance. The resist formulated with this polymer and cast in a water-ethanol mixture, showed 0.7 μm line and space patterns using a mercury-xenone lamp in a contact printing mode and pure water as a developer.

  18. A novel glyceryl monoolein-bearing cubosomes for gambogenic acid: Preparation, cytotoxicity and intracellular uptake.

    PubMed

    Luo, Qing; Lin, Tongyuan; Zhang, Cai Yuan; Zhu, Tingting; Wang, Lei; Ji, Zhaojie; Jia, Buyun; Ge, Tao; Peng, Daiyin; Chen, Weidong

    2015-09-30

    Lyotropic cubic liquid crystalline nanoparticles, also known as 'cubosomes', have been tested as effective carriers for a variety of drugs due to their ability to enhance delivery efficiency and reduced drug side effects. Cubosomes are colloidal carriers composed of biodegradable Glyceryl monooleate and F127. Being composed of well tolerable and physiological materials, these carriers are well tolerated, compatible and non-toxic. In this study, therefore, we developed a novel, water-soluble, glyceryl monooleate and F127 based multiblock copolymer for Gambogenic acid (GNA) by emulsion-evaporation and low temperature-solidification technique. Physicochemical properties, in vitro cytotoxicity, cellular uptake and in vivo pharmacokinetic of GNA-loaded cubosomes (GNA-Cubs) were investigated. The results revealed that GNA-Cubs were spherical or ellipsoidal monocellular by dynamic light scattering, meanwhile, 150-250nm in mean size with narrow polydispersity indexas determined by transmission electron microscopy. Small angle X-ray scattering indicated that GNA-Cubs retain the Pn3m cubic symmetry. Compared with GNA solution, GNA-Cubs exhibited markedly prolonged inhibitory activity in SMMC-7721 cells, as well as time-dependent increases in intra-cellular uptake. Furthermore, in vivo pharmacokinetic study showed that the Cmax values and the AUC of GNA-Cubs were higher than GNA solution approximately 1.2-fold and 9.1-fold, respectively. In conclusion, the results showed that the cubic liquid crystalline nanoparticles could be a potentially nanocarrier in the delivery of GNA for cancer therapy. PMID:26209071

  19. Dietary Nitrate Lowers Blood Pressure: Epidemiological, Pre-clinical Experimental and Clinical Trial Evidence.

    PubMed

    Gee, Lorna C; Ahluwalia, Amrita

    2016-02-01

    Nitric oxide (NO), a potent vasodilator critical in maintaining vascular homeostasis, can reduce blood pressure in vivo. Loss of constitutive NO generation, for example as a result of endothelial dysfunction, occurs in many pathological conditions, including hypertension, and contributes to disease pathology. Attempts to therapeutically deliver NO via organic nitrates (e.g. glyceryl trinitrate, GTN) to reduce blood pressure in hypertensives have been largely unsuccessful. However, in recent years inorganic (or 'dietary') nitrate has been identified as a potential solution for NO delivery through its sequential chemical reduction via the enterosalivary circuit. With dietary nitrate found in abundance in vegetables this review discusses epidemiological, pre-clinical and clinical data supporting the idea that dietary nitrate could represent a cheap and effective dietary intervention capable of reducing blood pressure and thereby improving cardiovascular health. PMID:26815004

  20. Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate.

    PubMed

    Jeong, Kyu Ho; Woo, Hye Seung; Kim, Chae Jin; Lee, Kyung Hwa; Jeon, Jun Young; Lee, Sang Young; Kang, Jae-Hoon; Lee, Sangkil; Choi, Young Wook

    2015-11-10

    A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 μm with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution- or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40°C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities--including PRE-lactam--was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations. PMID:26315121

  1. 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. PMID:24858389

  2. Glyceryl monooleate-based otic delivery system of ofloxacin: release profile and bactericidal activity.

    PubMed

    Adwan, Samer; Abu-Dahab, Rana; Al-Bakri, Amal G; Sallam, Alsayyed

    2015-05-01

    This study investigated the preparation and characterization of glyceryl monooleate- (GMO) based drug delivery system containing ofloxacin for the treatment of otitis externa. Acetate buffer (pH 4.5) containing dissolved ofloxacin was added to molten GMO as an aqueous phase, this resulted in the formation of a cubic and a reverse hexagonal phases. The release behavior of ofloxacin from the drug delivery system was studied using three different methods. The mechanism of drug release using paddles/dissolution apparatus and Franz diffusion cells followed Higuchi and Fickian diffusion models; whereas intrinsic release rate method showed zero-order kinetics. The intrinsic release rate was estimated and found to be 187.2 µg/cm(2)/h. The release mechanisms were similar irrespective of the loaded ofloxacin amount, however, the higher drug load displayed higher release rate. The drug delivery system was proven to be microbiologically effective by using agar diffusion method, against Staphylococcus aureus, and Pseudomonas aeruginosa. The GMO/ofloxacin formulation was stable for 6 months after preparation at room temperature as measured with respect to phase stability and antibacterial activity. PMID:24392877

  3. 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. PMID:18802845

  4. A novel method for the synthesis of glyceryl monocaffeate by the enzymatic transesterification and kinetic analysis.

    PubMed

    Sun, Shangde; Hu, Bingxue

    2017-01-01

    A novel enzymatic method for glyceryl monocaffeate (GMC) preparation by the transesterification of ethyl caffeate (EC) was investigated. The effects of reaction variables (reaction pressure, temperature, reaction time, enzyme load, and substrate ratio) on the enzymatic transesterification were studied and optimized using response surface methodology. HPLC-ESI-MS and HPLC-UV were used to monitor the transesterification. Thermodynamics, kinetic analyses and reaction mechanism were also evaluated. Results showed that, GMC can be successfully prepared by the enzymatic transesterification of EC with glycerol. Under the optimal conditions (enzyme load 22.54%, EC:glycerol=1:12.75 (mol/mol), 72.5°C, and 10.5h), EC conversion and GMC yield were 97.9±0.7% and 95.8±1.0%, respectively. The activation energies (Ea) for EC conversion and GMC formation were 44.23 and 46.51kJ/mol, respectively. The kinetic values for Vmax, Km(') and KIA were 2.18×10(-3)mol/(Lmin), 0.086mol/L, and 0.52mol/L, respectively. The transesterification mechanism with EC inhibition was also proposed. PMID:27507465

  5. Nitrovasodilator-induced relaxation and tolerance development in porcine vena cordis magna: dependence on intact endothelium.

    PubMed Central

    Kojda, G.; Beck, J. K.; Meyer, W.; Noack, E.

    1994-01-01

    1. Isolated segments of porcine vena cordis magna exhibited a reproducible contractile activity upon application of prostaglandin F2 alpha (PGF2 alpha) or KCl, that was independent of the presence of intact endothelium. Substance P (3 nM) elicited strictly endothelium-dependent relaxations amounting to 46.1 +/- 1.4% (n = 206) of contractions induced by 10 microM PGF2 alpha. 2. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a compound that spontaneously liberates nitric oxide, concentration-dependently relaxed PGF2 alpha-precontracted (50 microM) venous segments. Tolerance induction (incubation with 100 microM SNAP for 30 min) within the same segments resulted in a 3 fold attenuation of this effect, which was not further reduced after additional preincubation with glyceryl trinitrate (GTN). Removal of endothelium or the presence of N omega-nitro-L-arginine methylester (L-NAME) significantly improved the potency of SNAP before and after tolerance induction. 3. Concentration-dependent relaxations induced by GTN in non-tolerant veins were similar in the presence and absence of endothelium but much more reduced in tolerant endothelium-denuded (75 fold) compared to intact (20 fold) segments. In contrast, the presence of L-NAME significantly improved GTN-activity solely in non-tolerant veins, which, therefore, also resulted in a more pronounced attenuation of activity due to tolerance induction (100 fold). Preincubation of intact veins with SNAP also reduced GTN-activity but to a lesser extent (10 fold). 4. The more delayed but much longer, and compared to GTN somewhat weaker, acting new nitrovasodilator N-(3-nitrato-pivaloyl)-1-cysteineethylester (SPM 3672) was more potent in denuded than intact non-tolerant venous segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7521258

  6. Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2−/− mice

    PubMed Central

    Wenzel, P; Hink, U; Oelze, M; Seeling, A; Isse, T; Bruns, K; Steinhoff, L; Brandt, M; Kleschyov, A L; Schulz, E; Lange, K; Weiner, H; Lehmann, J; Lackner, K J; Kawamoto, T; Münzel, T; Daiber, A

    2007-01-01

    Background and purpose: Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 critically depends on the number of nitrate groups within the nitrovasodilator. Experimental approach: Nitrates with one (PEMN), two (PEDN; GDN), three (PETriN; glyceryl trinitrate, GTN) and four (pentaerithrityl tetranitrate, PETN) nitrate groups were investigated. Vasodilatory potency was measured in isometric tension studies using isolated aortic segments of wild type (WT) and ALDH-2−/− mice. Activity of the cGMP-dependent kinase-I (reflected by levels of phosphorylated VAsodilator Stimulated Phosphoprotein, P-VASP) was quantified by Western blot analysis, mitochondrial dehydrogenase activity by HPLC. Following incubation of isolated mitochondria with PETN, PETriN-chromophore and PEDN, metabolites were quantified using chemiluminescence nitrogen detection and mass spectrometry. Key results: Compared to WT, vasorelaxation in response to PETN, PETriN and GTN was attenuated about 10fold in ALDH-2−/− mice, identical to WT vessels preincubated with inhibitors of ALDH-2. Reduced vasodilator potency correlated with reduced P-VASP formation and diminished biotransformation of the tetranitrate- and trinitrate-compounds. None of these findings were observed for PEDN, GDN and PEMN. Conclusions and implications: Our results support the crucial role of ALDH-2 in bioactivating highly reactive nitrates like GTN, PETN and PETriN. ALDH-2-mediated relaxation by organic nitrates therefore depends mainly on the number of nitrate groups. Less potent nitrates like PEDN, GDN and PEMN are apparently biotransformed by other pathways. PMID:17220910

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

    PubMed

    Su, Cathy; Allum, Allison J; Aizawa, Yasushi; Kato, Takamitsu A

    2016-08-01

    Glyceryl glucoside (GG, α-d-glucosyglycerol) is a natural glycerol derivative found in alcoholic drinks. Recently GG has been used as an alternative for glycerol in cosmetic products. However, the safety of using GG is still unclear. Currently, dimethyl sulfoxide (DMSO) and glycerol are wildly used in cryopreservation. Despite GG being a derivative of glycerol, the ability of GG in cryopreservation is still unknown. By using a system of Chinese Hamster Ovary cells (CHO), A549 cells and AG1522 cells, the study examined the cryoprotective effects of DMSO, glycerol and GG. Cytotoxic and genotoxic responses induced by the three chemicals were also investigated with CHO to determine the safety of GG for cosmetic products. Our data suggests that GG has great cryopresearvation ability in the concentration of 30%-40% (v/v). For cytotoxic studies, DMSO showed the highest cytotoxicity above 3% (v/v) in cell doubling time delay among three chemicals. For the acute cytotoxicity with trypan blue dye exclusion assay, GG showed stronger cell killing effect within 24 h above 4% (v/v). For the continuous cytotoxicity with colony formation assay for 7 days, DMSO showed significantly reduced clonogenic ability above 2%. In genotoxicity studies, CHO treated with glycerol at 2% concentration induced three times higher frequencies of sister chromatid exchange (SCE) than background levels. GG did not induce significant amounts of SCE compared to background. Micronuclei formation was equally observed in the 2% and above concentrations of glycerol and GG. Our data showed that GG has significant effects on cryopreservation compared to DMSO. Glycerol and GG have similar cytotoxicity effects to CHO, but glycerol induced genotoxic responses in the same concentration. Therefore, we conclude that GG may be a safer alternative compound to glycerol in cosmetic products and safer alternative to DMSO in cryopreservation. PMID:27235553

  8. Chitosan and glyceryl monooleate nanostructures containing gemcitabine: potential delivery system for pancreatic cancer treatment.

    PubMed

    Trickler, William J; Khurana, Jatin; Nagvekar, Ankita A; Dash, Alekha K

    2010-03-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer. PMID:20238190

  9. The Z' = 12 superstructure of Λ-cobalt(III) sepulchrate trinitrate governed by C-H...O hydrogen bonds.

    PubMed

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

    2016-06-01

    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 6a_{h}\\times\\sqrt{3}b_{h}\\times c_{h} 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

  10. 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

  11. Roles of potassium ions, acetyl and L-glyceryl groups in native gellan double helix: an X-ray study.

    PubMed

    Chandrasekaran, R; Radha, A; Thailambal, V G

    1992-02-01

    Native gellan, the natural form of the polysaccharide excreted by the bacterium Pseudomonas elodea, has a tetrasaccharide repeating unit that contains L-glycerol and acetate ester groups, and forms only weak and elastic gels. Based on X-ray diffraction data from well oriented and polycrystalline fibers of its potassium salt, the crystal structure of native gellan, including ions and water, has been determined and refined to a final R-value of 0.17. The molecule forms of a half-staggered, parallel, double helix of pitch 5.68 nm which is stabilized by hydrogen bonds involving the hydroxymethyl groups in one chain and both carboxylate and glyceryl groups in other. Two molecules are packed in an antiparallel fashion in a trigonal unit cell of side a = 1.65 nm. Although the gross molecular morphology and packing arrangements are isomorphous with those observed in the crystal structure of potassium gellan, which is devoid of any substitutions, native gellan exhibits exceptional changes in its ion binding characteristics with respect to gellan. In particular, the L-glyceryl groups do not allow the gellan-like coordinated interactions of the ions and the carbohydrate groups, within and between double helices, which are necessary for strong gelation. These results at the molecular level explain, for the first time, the differences in the behavior of the polymer with and without substitutions. PMID:1591755

  12. Formulation of an oral dosage form utilizing the properties of cubic liquid crystalline phases of glyceryl monooleate.

    PubMed

    Sallam, Al-Sayed; Khalil, Enam; Ibrahim, Hussain; Freij, Ibtisam

    2002-05-01

    Glyceryl monooleate is a Food and Drug Administration-approved food additive which has the ability to form various liquid crystalline phases in the presence of various amounts of water. The unique properties of the cubic liquid crystalline phase that result upon the presence of excess body fluids at body temperature were utilized to formulate an oral dosage form containing furosemide as the model drug. The aim was to develop a formula, which has both bioadhesive and sustained release properties of the resultant cubic phase, so that increasing gastric residence time to improve bioavailability of the drug and at the same time obtaining a sustained action. The system was found to be affected by the limited solubility of furosemide in both the carrier system and the pH of surrounding medium. As a consequence, the addition of some solubility modifiers was investigated in order to obtain the desired properties of the expected liquid crystalline system. PMID:11976023

  13. 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.

  14. 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.

    2016-01-01

    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 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.

  15. 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.

  16. Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization.

    PubMed

    Andrews, Karen L; Sampson, Amanda K; Irvine, Jennifer C; Shihata, Waled A; Michell, Danielle L; Lumsden, Natalie G; Lim, Chloe; Huet, Olivier; Drummond, Grant R; Kemp-Harper, Barbara K; Chin-Dusting, Jaye P F

    2016-09-01

    Nitroxyl anion (HNO) donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure. Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leucocyte adhesion to the endothelium and macrophage polarization. Similar to the NO donor glyceryl trinitrate (GTN), the HNO donors Angeli's salt (AS) and isopropylamine NONOate (IPA/NO) decreased leucocyte adhesion to activated human umbilical vein endothelial cells (HUVECs) and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in intercellular adhesion molecule-1 (ICAM-1) and the cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) which was inhibitor of nuclear factor κB (NFκB) α (IκBα)- and subsequently NFκB-dependent. Intriguingly, the effects of AS on leucocyte adhesion, like those on vasodilation, were found to not be susceptible to pharmacological tolerance, unlike those observed with GTN. As well, HNO reduces monocyte activation and promotes polarization of M2 macrophages. Taken together, our data demonstrate that HNO donors can reduce factors that are associated with and which precede atherosclerosis and may thus be useful therapeutically. Furthermore, since the effects of the HNO donors were not subject to tolerance, this confers an additional advantage over NO donors. PMID:27231254

  17. Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl arachidonate using in vitro diffusion cell techniques.

    PubMed

    Eppler, A R; Kraeling, M E K; Wickett, R R; Bronaugh, R L

    2007-11-01

    Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA. PMID:17602815

  18. Liquid crystalline systems of phytantriol and glyceryl monooleate containing a hydrophilic protein: Characterisation, swelling and release kinetics.

    PubMed

    Rizwan, S B; Hanley, T; Boyd, B J; Rades, T; Hook, S

    2009-11-01

    Swelling and phase behaviour of phytantriol and glyceryl monooleate (GMO) matrices with varying water loadings were investigated. Release of a model protein, FITC-Ova was subsequently examined. Polarised light microscopy and small angle X-ray scattering analysis showed that the addition of FITC-Ova only altered the liquid crystalline structure of phytantriol matrices at low water loadings, and that postrelease study, the phase structure of matrices at both low and high loading reflected that of the binary system. Addition of FITC-Ova to GMO matrices also altered the liquid crystalline structure when compared to the respective binary system at low but not at high loading. All samples analysed after the release study had transformed to the reverse hexagonal phase (H(II)). Swelling studies revealed a faster and more extensive swelling of GMO when compared to phytantriol. Release of FITC-Ova from phytantriol matrices was faster and occurred to a greater extent most likely due to the conversion of GMO matrices into the H(II) phase. No effect on release as a function of initial water content was observed for either lipid. We have confirmed that phytantriol based liquid crystalline matrices can sustain the release of a hydrophilic protein, suggesting its suitability as a potential sustained antigen-delivery system. PMID:19340889

  19. Interspecific Utility of Microsatellites in Fish: A Case Study of (CT)(n) and (GT)(n) Markers in the Shanny Lipophrys pholis (Pisces: Blenniidae) and Their Use in Other Blennioidei.

    PubMed

    Guillemaud; Almada; Serrão Santos R; Cancela

    2000-05-01

    We report the development of new microsatellite markers that can be used for population analyses in the shanny Lipophrys pholis. The procedure involved the construction of a microsatellite-enriched genomic bank. Five (GT)(n) and (CT)(n) microsatellites have been characterized, four of which are polymorphic. The analysis of one population allowed us to verify their usefulness as markers in population studies. Moreover, interspecific amplifications have been performed using primers defined in other species to amplify Lipophrys pholis, or using the primers defined in Lipophrys pholis to amplify other species. We use these results to discuss the hypothesis that microsatellites are highly conserved in fish. PMID:10852803

  20. Glyceryl monooleyl ether-based liquid crystalline nanoparticles as a transdermal delivery system of flurbiprofen: characterization and in vitro transport.

    PubMed

    Uchino, Tomonobu; Murata, Akiko; Miyazaki, Yasunori; Oka, Toshihiko; Kagawa, Yoshiyuki

    2015-01-01

    Liquid crystalline nanoparticles (LCNs) were prepared using glyceryl monooleyl ether (GME) by the modified film rehydration method. Hydrogenated lecithin (HL), 1,3-butylene glycol (1,3-BG), and Poloxamer 407 were used as additives. The prepared LCN formulations were evaluated based on particle size, small-angle X-ray diffraction (SAXS) analysis, (1)H- and (19)F-NMR spectra, and in vitro skin permeation across Yucatan micropig skin. The composition (weight percent) of the LCN formulations were GME-HL-1,3-BG (4 : 1 : 15), 4% GME-based LCN and GME-HL-1,3-BG (8 : 1 : 15), 8% GME-based LCN and their mean particle sizes were 130-175 nm. Flurbiprofen 5 and 10 mg was loaded into 4% GME-based LCN and 8% GME-based LCN systems, respectively. The results of SAXS and NMR suggested that both flurbiprofen-loaded formulations consist of particles with reverse type hexagonal phase (formation of hexosome) and flurbiprofen molecules were localized in the lipid domain through interaction of flurbiprofen with the lipid components. Flurbiprofen transport from the LCN systems across the Yucatan micropig skin was increased compared to flurbiprofen in citric buffer (pH=3.0). The 8% GME-based LCN systems was superior to the 4% GME-based LCN for flurbiprofen transport. Since the internal hexagonal phase in the 8% GME-based LCN systems had a higher degree of order compared to the 4% GME-based LCN in SAXS patterns, the 8% GME-based LCN system had a larger surface area, which might influence flurbiprofen permeation. These results indicated that the GME-based LCN system is effective in improving the skin permeation of flurbiprofen across the skin. PMID:25948327

  1. Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages.

    PubMed

    Yeh, J L; Hsu, J H; Hong, Y S; Wu, J R; Liang, J C; Wu, B N; Chen, I J; Liou, S F

    2011-01-01

    Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced upregulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced by LPS. Moreover, they both attenuated the DNA binding of NF-kB and AP-1, phosphorylation of inhibitory kB-alpha (IkB-alpha), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERK1/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kB and AP-1 through inhibition of MAPKs and Akt/IkB-alpha signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases. PMID:21658309

  2. S-nitrosothiols as vasodilators: implications regarding tolerance to nitric oxide-containing vasodilators.

    PubMed Central

    Henry, P. J.; Drummer, O. H.; Horowitz, J. D.

    1989-01-01

    1. The formation of an S-nitrosothiol compound, S-nitroso-N-acetylcysteine (SNAC) has recently been proposed to mediate the augmentation of the anti-aggregatory and haemodynamic effects of glyceryl trinitrate observed in the presence of N-acetylcysteine. This study investigated the effects on an isolated coronary artery preparation of acute and prolonged exposure to S-nitrosothiol compounds and nitric oxide (NO). 2. Single doses of NO and of the S-nitrosothiol compounds, SNAC and S-nitroso-N-acetyl-penicillamine (SNAP), induced rapid, but transient, relaxations in U46619-contracted bovine isolated coronary artery rings. Peak relaxation responses to SNAP and NO were attenuated in the presence of N-acetylcysteine, cysteine, ascorbic acid and methylene blue. The duration of the relaxation responses to SNAC was two to three times longer than those to SNAP and NO. In the presence of N-acetylcysteine (but not cysteine, ascorbic acid or methylene blue) the duration of the relaxation responses to SNAP and NO (but not to SNAC) was markedly increased. H.p.l.c. assay confirmed that, in the presence of N-acetylcysteine, SNAP and, to a lesser degree, NO were converted to the relatively more stable and longer acting vasodilator, SNAC. 3. When compared to control rings, coronary artery rings superfused with glyceryl trinitrate were subsequently markedly less responsive to the vasodilator actions of glyceryl trinitrate, whereas responsiveness to SNAC or NO was only marginally reduced. On the other hand, coronary artery rings superfused with SNAC or NO were subsequently less responsive to glyceryl trinitrate, SNAC and NO. Thus prolonged vascular exposure to SNAC or NO induced a form of tolerance different from that induced with glyceryl trinitrate and which is possibly associated with impaired guanylate cyclase activity. 4. Coronary artery rings superfused with NO were markedly less responsive to glyceryl trinitrate and NO, whereas responses to the endothelium-dependent vasodilator

  3. 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

  4. Nitric oxide (NO)--biogeneration, regulation, and relevance to human diseases.

    PubMed

    Bian, Ka; Murad, Ferid

    2003-01-01

    On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine and Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system. In contrast with the short research history of the enzymatic synthesis of NO, the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin; GTN) is the first compound of this category. Alfred Nobel (the founder of Nobel Prize) himself had suffered from angina pectoris and was prescribed nitroglycerin for his chest pain. Almost a century later, research in the NO field has dramatically extended and the role of NO in physiology and pathology has been extensively studied. The steady-state concentration and the biological effects of NO are critically determined not only by its rate of formation, but also by its rate of decomposition. Biotransformation of NO and its related N-oxides occurs via different metabolic routes within the body and presents another attractive field for our research as well as for the venture of drug discovery. PMID:12456375

  5. Resiniferatoxin and piperine: capsaicin-like stimulators of oxygen uptake in the perfused rat hindlimb.

    PubMed

    Eldershaw, T P; Colquhoun, E Q; Bennett, K L; Dora, K A; Clark, M G

    1994-01-01

    The naturally occurring capsaicin-like molecules, resiniferatoxin (RTX, Euphorbia spp.) and piperine (Piper nigrum), each stimulated oxygen uptake (VO2) in association with increased vascular resistance in a concentration-dependent manner when infused into the perfused rat hindlimb. 5 microM glyceryl trinitrate (GTN, a nitrovasodilator) significantly blocked the oxygen and pressure responses to both RTX and piperine, indicating a close relationship between changes in VO2 and the vasoconstriction. Concentrations greater than those required for maximal VO2 resulted in an inhibition of VO2, although perfusion pressure continued to increase. Time course studies showed that both RTX and piperine at high doses resulted in a tri-phasic response. An initial phase of transient VO2 stimulation was followed by a second phase of inhibition. A third phase involving an often larger but transient stimulation of VO2 followed removal of the agents and continued after the pressure returned to basal. The actions of RTX and piperine were similar to those of other active capsaicin-like molecules tested previously in this system, including capsaicinoids (Capsicum spp.), gingerols (Zingiber officinale), and shogoals (Zingiber officinale). RTX was the most potent, and piperine the least potent of this series. Although receptor involvement has yet to be unequivocally established, the data are consistent with the presence of a functional capsaicin-like (vanilloid) receptor in the vasculature of the rat hindlimb that mediates vasoconstriction and oxygen uptake. These findings may have implications for the future development of thermogenic agents. PMID:8035653

  6. Impaired vasodilator response to organic nitrates in isolated basilar arteries

    PubMed Central

    Martens, Dorothee; Kojda, Georg

    2001-01-01

    The differential responsiveness of various sections and regions in the vascular system to the vasodilator activity of organic nitrates is important for the beneficial antiischaemic effects of these drugs. In this study we examined the vasodilator activity of organic nitrates in cerebral arteries, where vasodilation causes substantial nitrate induced headache. Isolated porcine basilar and coronary arteries were subjected to increasing concentrations of glyceryl trinitrate (GTN), isosorbide-5-nitrate (ISMN) and pentaerythritol tetranitrate (PETN). S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and endothelium-dependent vasodilation was investigated for comparison purpose. The vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.33±0.1, n=8), ISMN (1.61±0.07, n=7) and PETN (>10 μM, n=7) in basilar arteries was more than 100 fold lower than that of GTN (6.52±0.06, n=12), ISMN (3.66±0.08, n=10) and PETN (6.3±0.13, n=8) observed in coronary arteries. In striking contrast, the vasodilator potency of SNAP (halfmaximal effective concentration in −logM) was almost similar in basilar (7.76±0.05, n=7) and coronary arteries (7.59±0.05, n=9). Likewise, no difference in endothelium dependent relaxation was observed. Denudation of the endothelium resulted in a small increase of the vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.84±0.09, n=7, P<0.03) in basilar arteries and similar results were obtained in the presence of the NO-synthase inhibitor Nω-nitro-L-arginine (4.59±0.05, n=9, P<0.03). These results suggest that cerebral conductance blood vessels such as porcine basilar arteries seems to have a reduced expression and/or activity of certain cellular enzymatic electron transport systems such as cytochrome P450 enzymes, which are necessary to bioconvert organic nitrates to NO. PMID:11156558

  7. A prospective randomized longitudinal study involving 6 months of endurance or resistance exercise. Conduit artery adaptation in humans.

    PubMed

    Spence, Angela L; Carter, Howard H; Naylor, Louise H; Green, Daniel J

    2013-03-01

    Abstract  This randomized trial evaluated the impact of different exercise training modalities on the function and size of conduit arteries in healthy volunteers. Young (27 ± 5 years) healthy male subjects were randomized to undertake 6 months of either endurance training (ET; n = 10) or resistance training (RT; n = 13). High-resolution ultrasound was used to determine brachial, femoral and carotid artery diameter and wall thickness (IMT) and femoral and brachial flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-mediated dilatation. Improvements in peak oxygen uptake occurred with ET (from 3.6 ± 0.7 to 3.8 ± 0.6 l min(-1), P = 0.024) but not RT. Upper body muscular strength increased following RT (from 57.8 ± 17.7 to 69.0 ± 19.5 kg, P < 0.001), but not ET. Both groups exhibited increases in lean body mass (ET, 1.4 ± 1.8 kg and RT, 2.3 ± 1.3 kg, P < 0.05). Resistance training increased brachial artery resting diameter (from 3.8 ± 0.5 to 4.1 ± 0.4 mm, P < 0.05), peak FMD diameter (+0.2 ± 0.2 mm, P < 0.05) and GTN-mediated diameter (+0.3 ± 0.3 mm, P < 0.01), as well as brachial FMD (from 5.1 ± 2.2 to 7.0 ± 3.9%, P < 0.05). No improvements in any brachial parameters were observed following ET. Conversely, ET increased femoral artery resting diameter (from 6.2 ± 0.7 to 6.4 ± 0.6 mm, P < 0.05), peak FMD diameter (+0.4 ± 0.4 mm, P < 0.05) and GTN-induced diameter (+0.3 ± 0.3 mm, P < 0.05), as well as femoral FMD-to-GTN ratio (from 0.6 ± 0.3 to 1.1 ± 0.8, P < 0.05). Resistance training did not induce changes in femoral artery parameters. Carotid artery IMT decreased in response to both forms of training. These findings indicate that 6 months of supervised exercise training induced changes in brachial and femoral artery size and function and decreased carotid artery IMT. These impacts of both RT and ET would be expected to translate to decreased cardiovascular risk. PMID:23247114

  8. Glyceryl monooleate/poloxamer 407 cubic nanoparticles as oral drug delivery systems: I. In vitro evaluation and enhanced oral bioavailability of the poorly water-soluble drug simvastatin.

    PubMed

    Lai, Jie; Chen, Jianming; Lu, Yi; Sun, Jing; Hu, Fuqiang; Yin, Zongning; Wu, Wei

    2009-01-01

    Glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were investigated as potential oral drug delivery systems to enhance the bioavailability of the water-insoluble model drug simvastatin. The simvastatin-loaded cubic nanoparticles were prepared through fragmentation of the GMO/poloxamer 407 bulk cubic-phase gel using high-pressure homogenization. The internal structure of the cubic nanoparticles was identified by cryo-transmission electron microscopy. The mean diameter of the cubic nanoparticles varied within the range of 100-150 nm, and both GMO/poloxamer 407 ratio and theoretical drug loading had no significant effect on particle size and distribution. Almost complete entrapment with efficiency over 98% was achieved due to the high affinity of simvastatin to the hydrophobic regions of the cubic phase. Release of simvastatin from the cubic nanoparticles was limited both in 0.1 M hydrochloride solution containing 0.2% sodium lauryl sulfate and fasted-state simulated intestinal fluid with a total release of <3.0% at 10 h. Pharmacokinetic profiles in beagle dogs showed sustained plasma levels of simvastatin for cubic nanoparticles over 12 h. The relative oral bioavailability of simvastatin cubic nanoparticles calculated on the basis of area under the curve was 241% compared to simvastatin crystal powder. The enhancement of simvastatin bioavailability was possibly attributable to facilitated absorption by lipids in the formulation rather than improved release. PMID:19636709

  9. Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endothelium-dependent vasodilation

    PubMed Central

    Soloviev, Anatoly I; Tishkin, Sergey M; Parshikov, Alexander V; Ivanova, Irina V; Goncharov, Eugene V; Gurney, Alison M

    2003-01-01

    Gamma radiation impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about radiation effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rabbits subjected to whole-body irradiation from a cobalt60 source. The endothelium-dependent relaxation of rabbit aorta evoked by acetylcholine (ACh) or A23187 was impaired in a dose-dependent manner by irradiation at 2 Gy or above. Inhibition was evident 9 days post-irradiation and persisted over the 30 day experimental period. Endothelium-independent responses to glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1) were suppressed over a similar dose range at 7–9 days post-irradiation, but recovered fully by 30 days post-irradiation. In healthy vessels, ACh-induced relaxation was inhibited by L-Nω-nitroarginine (L-NA; 3×10−4 M) and charybdotoxin (10−8 M) plus apamin (10−6 M) but resistant to indomethacin, indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). Supporting this, ACh caused smooth muscle hyperpolarization that was reduced by L-NA and charybdotoxin plus apamin. In irradiated vessels, responses to ACh were insensitive to L-NA but abolished by charybdotoxin plus apamin, indicating selective loss of NO-mediated relaxation. In animals treated shortly after irradiation with the antioxidant, α-tocopherol acetate, the NO-dependent relaxation was restored without effect on the EDHF-dependent component. The results imply that radiation selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level. PMID:12642385

  10. Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats and humans

    PubMed Central

    Arif, Sayqa; Borgognone, Alessandra; Lin, Erica Lai-Sze; O'Sullivan, Aine G; Sharma, Vishal; Drury, Nigel E; Menon, Ashvini; Nightingale, Peter; Mascaro, Jorge; Bonser, Robert S; Horowitz, John D; Feelisch, Martin; Frenneaux, Michael P; Madhani, Melanie

    2015-01-01

    Background and Purpose Hypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature. Experimental Approach The role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra-arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance-independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors. Key Results Both in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non-significant trend towards attenuation of nitrite-mediated increases in FBF. Conclusions and Implications In human and rat vascular tissue in vitro, hypoxic nitrite-mediated vasodilatation involves ALDH2. In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms. PMID:25754766

  11. Complete denitration of nitroglycerin by bacteria isolated from a washwater soakaway.

    PubMed

    Marshall, S J; White, G F

    2001-06-01

    Four axenic bacterial species capable of biodegrading nitroglycerin (glycerol trinitrate [GTN]) were isolated from soil samples taken from a washwater soakaway at a disused GTN manufacturing plant. The isolates were identified by 16S rRNA gene sequence homology as Pseudomonas putida, an Arthrobacter species, a Klebsiella species, and a Rhodococcus species. Each of the isolates utilized GTN as its sole nitrogen source and removed nitro groups sequentially from GTN to produce glycerol dinitrates and mononitrates (GMN), with the exception of the Arthrobacter strain, which achieved removal of only the first nitro group within the time course of the experiment. The Klebsiella strain exhibited a distinct preference for removal of the central nitro group from GTN, while the other five strains exhibited no such regioselectivity. All strains which removed a second nitro group from glycerol 1,2-dinitrate showed regiospecific removal of the end nitro group, thereby producing glycerol 2-mononitrate. Most significant was the finding that the Rhodococcus species was capable of removing the final nitro group from GMN and thus achieved complete biodegradation of GTN. Such complete denitration of GTN has previously been shown only in mixed bacterial populations and in cultures of Penicillium corylophilum Dierckx supplemented with an additional carbon and nitrogen source. Hence, to the best of our knowledge, this is the first report of a microorganism that can achieve complete denitration of GTN. PMID:11375172

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

    PubMed Central

    Walter, Roland; Mark, Michael; Gaudenz, Roman; Harris, Llinos G; Reinhart, Walter H

    1999-01-01

    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.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.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. PMID:10516657

  13. 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. PMID:26473355

  14. 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

  15. 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

  16. Nitroglycerin dinitrate metabolites do not affect the pharmacokinetics and pharmacodynamics of nitroglycerin in the dog: a preliminary report.

    PubMed

    Lee, F W; Hu, J; Metzler, C H; Benet, L Z

    1993-04-01

    Studies were carried out in conscious dogs to determine the effects of 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN) on nitroglycerin (GTN) pharmacokinetics and pharmacodynamics. In the first set of experiments, steady state plasma levels (Css) of either 1,2-GDN or 1,3-GDN in three dogs were rapidly achieved by giving an iv bolus (77 micrograms/kg), followed immediately by an infusion (50 micrograms/min) of the same GDN. A single iv bolus dose of GTN (0.025 micrograms/kg) was given 50 min after beginning the GDN infusion and compared with plasma concentrations following a similar GTN dose in the absence of dosed GDNs. No significant differences in GTN AUC (p > 0.9) and CL(app) (p > 0.7) were found. In a second set of experiments, an infusion of nitroglycerin was begun in each of 4 dogs and continued for 160 min at an infusion rate of 100 micrograms/min. Steady state concentrations of GTN were achieved within 100 min, at which time the dog received, simultaneously, an iv bolus dose (5.14 mg) of one of the GDNs and an infusion dose (100 micrograms/min) of the same GDN. For both dinitrate metabolites no significant differences (p > 0.5) were found between control and interaction arterial and venous clearances, although venous GTN clearances tended to decrease in the presence of dosed GDNs. Steady state systolic blood pressure during GDN infusions could be further reduced when GTN doses were administered; however, the steady state systolic blood pressure decrease caused by GTN could not be further reduced by the GDN infusions. Results suggest that the GDNs do not inhibit nitroglycerin metabolism or hemodynamics at the dose levels studied here. PMID:8229678

  17. Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

    PubMed

    Ferrari, L F; Levine, J D; Green, P G

    2016-03-11

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. PMID:26779834

  18. Recurrent myocardial infarction secondary to Prinzmetal’s variant angina

    PubMed Central

    Murdoch, Dale; Dhillon, Priyanka; Niranjan, Selvanayagam

    2015-01-01

    Prinzmetal’s variant angina describes chest pain secondary to reversible coronary artery vasospasm in the context of both diseased and non-diseased coronary arteries. Symptoms typically occur when the patient is at rest and are associated with transient ST-segment elevation. Acute episodes respond to glyceryl trinitrate, but myocardial infarction and other potentially fatal complications can occur, and long-term management can be challenging. Although it is not well understood, the underlying mechanism appears to involve a combination of endothelial damage and vasoactive mediators. In this case, a 35-year-old woman with myocardial infarction secondary to coronary artery vasospasm experienced recurrent chest pain. Coronary angiography revealed severe focal stenosis in the mid left anterior descending artery, which completely resolved after administration of intracoronary glyceryl trinitrate. The patient was discharged on nitrates and calcium channel blockers. The patient re-presented with another myocardial infarction, requiring up-titration of medical therapy. PMID:26034323

  19. 21 CFR 184.1328 - Glyceryl behenate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... acid made from glycerin and behenic acid (a saturated C22 fatty acid). The mixture contains... fatty acids. (2) Behenic acid. Between 80 and 90 percent of the total fatty acid content. (3) Acid...

  20. 21 CFR 184.1324 - Glyceryl monostearate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... glycerolysis of certain fats or oils that are derived from edible sources or by esterification, with glycerin, of stearic acid that is derived from edible sources. (b) The ingredient must be of a purity...

  1. 21 CFR 172.811 - Glyceryl tristearate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  2. 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...

  3. Statistical analysis plan for the 'Efficacy of Nitric Oxide in Stroke' (ENOS) trial.

    PubMed

    Bath, Philip M W; Houlton, Aimee; Woodhouse, Lisa; Sprigg, Nikola; Wardlaw, Joanna; Pocock, Stuart

    2014-04-01

    High blood pressure is common during the acute phase of stroke and is associated with a poor outcome. However, the management of high blood pressure remains unclear. The 'Efficacy of Nitric Oxide in Stroke' trial tested whether transdermal glyceryl trinitrate, a nitric oxide donor that lowers blood pressure, is safe and effective in improving outcome after acute stroke. Efficacy of Nitric Oxide in Stroke is an international multicenter, prospective, randomized, single-blind, blinded endpoint trial, with funding from the U.K. Medical Research Council. Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140-220 mmHg were randomized to glyceryl trinitrate or no glyceryl trinitrate and, where relevant, to continue or stop prestroke antihypertensive therapy. The primary outcome is shift in modified Rankin Scale at three-months. Patients or relatives gave written informed (proxy) consent, and all sites had research ethics approval. Analyses will be done by intention to treat. This paper and attachment describe the trial's statistical analysis plan, developed prior to unblinding of date. The statistical analysis plan contains design and methods for analyses, and unpopulated tables and figures for the two primary publications and some secondary publications. The database will be locked in late February 2014 in preparation for presentation of the results in May 2014. The data from the trial will improve the precision of the estimates of the overall treatment effects (efficacy and safety) of results from completed trials of blood pressure management in acute stroke, and provide the first large-scale randomized evidence on transdermal glyceryl trinitrate, and of continuing (vs. stopping) prestroke antihypertensive medications, in acute stroke. PMID:24588789

  4. 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

  5. Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide–cyclic GMP signalling

    PubMed Central

    Madhani, Melanie; Scotland, Ramona S; MacAllister, Raymond J; Hobbs, Adrian J

    2003-01-01

    The sensitivity of the particulate guanylate cyclase–cyclic guanosine-3′,5′-monophosphate (cGMP) system to atrial (ANP) and C-type (CNP) natriuretic peptides was investigated in aortae and mesenteric small arteries from wild-type (WT) and endothelial nitric oxide synthase (eNOS) knockout (KO) mice. ANP and CNP produced concentration-dependent relaxations of mouse aorta that were significantly attenuated by the natriuretic peptide receptor (NPR)-A/B antagonist HS-142-1 (10−5 M). Both ANP and CNP were more potent in aortae from eNOS KO mice compared to WT. The potency of ANP and CNP in aortae from WT animals was increased in the presence of the NOS inhibitor, NG-nitro-L-arginine (3 × 10−4 M) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolol[4,3,a]quinoxalin-1-one (5 × 10−6 M). In contrast, the potency of ANP and CNP in aortae from eNOS KO animals was reduced following pretreatment of tissues with supramaximal concentrations of the NO-donor, glyceryl trinitrate (3 × 10−5 M, 30 min) or ANP (10−7 M, 30 min). Responses to acetylcholine in aortae from WT mice (dependent on the release of endothelium-derived NO) were significantly reduced following pretreatment of tissues with GTN (3 × 10−5 M, 30 min) and ANP (10−7 M, 30 min). CNP and the NO-donor, spermine-NONOate caused concentration-dependent relaxations of mesenteric small arteries from WT animals that were significantly increased in eNOS KO mice compared to WT. ANP was unable to significantly relax mesenteric arteries from WT or eNOS KO animals. In conclusion, both NPR-A- and NPR-B-linked pGC pathways are modulated by NO–cGMP in murine aorta and mesenteric small arteries and crossdesensitisation occurs between NPR subtypes. The biological activity of endothelium-derived NO is also influenced by the ambient concentration of NO and natriuretic peptides. Such an autoregulatory pathway may represent an important physiological homeostatic mechanism and link the paracrine activity

  6. sGC-cGMP signaling: target for anticancer therapy.

    PubMed

    Bian, Ka; Murad, Ferid

    2014-01-01

    The biologic endogenous production of cGMP was reported in the 1960s and followed by the demonstration of guanylyl cyclase activity and the isoforms of soluble and membrane-bound guanylyl cyclases. During the same period, cGMP specific phosphodiesterases also was discovered. Murad's lab established link between the endothelium derived relaxation factor (EDRF) and elevated cGMP concentration in the vascular system. October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning nitric oxide (NO) as a signaling molecule in the cardiovascular system. In contrast with the short research history of the enzymatic synthesis of NO, the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin; GTN) is the first compound of this category. Alfred Nobel (the founder of the Nobel Prize) himself had suffered from angina pectoris and was prescribed nitroglycerin for his chest pain while he refused to take due to the induction of headaches. Almost a century after its first chemical use, research in the nitric oxide and 3',5'-cyclic guanosine monophosphate (NO/cGMP) pathway has dramatically expanded and the role of NO/cGMP in physiology and pathology has been extensively studied. Soluble guanylyl cyclase (sGC) is the receptor for NO. The α1β1 heterodimer is the predominant isoform of sGC that is obligatory for catalytic activity. NO binds to the ferrous (Fe(2+)) heme at histidine 105 of the β1 subunit and leads to an increase in sGC activity and cGMP production of at least 200-fold. In this chapter, we reviewed the studies of sGC-cGMP signaling in cell proliferation; introduced our work of targeting sGC-cGMP signaling for cancer therapy; and explored the role of sGC-cGMP signaling in the chromatin-microenvironment. PMID:25015797

  7. The effect of a national quality improvement collaborative on prehospital care for acute myocardial infarction and stroke in England

    PubMed Central

    2014-01-01

    Background Previous studies have shown wide variations in prehospital ambulance care for acute myocardial infarction (AMI) and stroke. We aimed to evaluate the effectiveness of implementing a Quality Improvement Collaborative (QIC) for improving ambulance care for AMI and stroke. Methods We used an interrupted time series design to investigate the effect of a national QIC on change in delivery of care bundles for AMI (aspirin, glyceryl trinitrate [GTN], pain assessment and analgesia) and stroke (face-arm-speech test, blood pressure and blood glucose recording) in all English ambulance services between January 2010 and February 2012. Key strategies for change included local quality improvement (QI) teams in each ambulance service supported by a national coordinating expert group that conducted workshops educating staff in QI methods to improve AMI and stroke care. Expertise and ideas were shared between QI teams who met together at three national workshops, between QI leads through monthly teleconferences, and between the expert group and participants. Feedback was provided to services using annotated control charts. Results We analyzed change over time using logistic regression with three predictor variables: time, gender, and age. There were statistically significant improvements in care bundles in nine (of 12) participating trusts for AMI (OR 1.04, 95% CI 1.04, 1.04), nine for stroke (OR 1.06, 95% CI 1.05, 1.07), 11 for either AMI or stroke, and seven for both conditions. Overall care bundle performance for AMI increased in England from 43 to 79% and for stroke from 83 to 96%. Successful services all introduced provider prompts and individualized or team feedback. Other determinants of success included engagement with front-line clinicians, feedback using annotated control charts, expert support, and shared learning between participants and organizations. Conclusions This first national prehospital QIC led to significant improvements in ambulance care for AMI and

  8. [Cardiovascular impact of end-stage renal insufficiency in children undergoing hemodialysis].

    PubMed

    Aggoun, Y; Niaudet, P; Laffont, A; Sidi, D; Kachaner, J; Bonnet, D

    2000-08-01

    Cardiac hypertrophy and arterial dysfunction have been described in end-stage renal disease (ESDR) in adults. The incremental elastic modulus (Einc), is a marker of vascular wall material stiffness and an independant predictor of cardiovascular mortality in adults with ESRD on hemodialysis. The relationship between arterial changes and the heart is unknown in the children with ESRD in the same conditions. Using a high-resolution vascular ultrasound and a computerized system of measurement (Iotec), we assessed noninvasively 10 ESRD patients (mean +/- SD, age, 11.5 +/- 4 years; blood pressure [BP], 120 +/- 10/63 +/- 4 mmHg) and 10 age-, sex-, and BP-matched controls (mean +/- SD, age, 11 +/- 4 years; BP, 114 +/- 8/58 +/- 8 mmHg). The systolic and diastolic diameter of the common carotid artery (CCA), the thickness of the wall (intima-media thickness, IMT), the cross sectional compliance (CSC), the cross sectional distensibility (CSD) and the (Einc) were determined. CSC and CSD were evaluated at the same level of pressure. The CCA pressure waveform was obtained by applanation tonometry to assess the reflected wave by the augmentation index (AI). Further the left ventricular mass index was assessed. The flow mediated dilation (FMD) (endothelium-dependent function) and the vasodilation induced by glyceryl-trinitrate (GTNMD) (GTN, an endothelium-independent dilator) were evaluated at the brachial artery site. Compared to control subjects, ESRD patients have mechanical artery dysfunction with lower CSC and CSD (0.11 +/- 0.04 vs 0.18 +/- 0.05 mm2.mmHg-1; p < 0.01; 0.43 +/- 0.10 vs 0.82 +/- 0.20 mmHg-1.10(-2); p < 0.001) and higher Einc (2.60 +/- 1.00 vs 1.40 +/- 0.30 mmHg.10(3); p < 0.001). Furthermore an earlier return of the reflected pulse wave (AI -0.24 +/- 0.08 vs -0.58 +/- 0.06; p < 0.005) is correlated to LV mass index (r = 0.55, P < 0.01) that is significantly increased (134 +/- 63 vs 69 +/- 25 g/m2; p < 0.005). These patients have an impaired FMD (4 +/- 2 vs 7

  9. Effects of buccal nitrate on left ventricular haemodynamics and volume at rest and during exercise-induced angina.

    PubMed Central

    Silke, B; Verma, S P; Frais, M A; Hafizullah, M; Taylor, S H

    1985-01-01

    A novel approach has been employed to characterize the effects of a cardioactive drug on left ventricular haemodynamics and volume by simultaneously determining cardiac stroke volume (thermodilution) and left ventricular ejection fraction (nuclear probe). The effects of glyceryl trinitrate were evaluated in 12 patients with angiographically proven coronary artery disease at rest and 3, 7, 15 and 30 min following 10 mg buccal nitroglycerin (Suscard) administration. The impact of the drug on left ventricular haemodynamics and volume during exercise-induced angina was determined by repeating exercise 30 min following drug administration, at the workload that reliably induced angina during control exercise. At rest buccal nitroglycerin reduced systemic arterial pressure, cardiac and stroke volume indices, and increased heart rate. The left ventricular ejection fraction (E.F.) increased; its filling pressure together with end-diastolic and end-systolic volumes were significantly reduced. Compared with control supine-bicycle exercise, the drug reduced mean systemic arterial pressure and left ventricular filling pressure without change in cardiac and stroke volume indices. There was a smaller increase in left ventricular volume during exercise, and the fall in E.F. was attenuated. These data demonstrated differential actions of glyceryl trinitrate on left ventricular function related to the physiological state in obstructive coronary artery disease. These techniques appear to hold promise in the evaluation of the effects of other therapies on left ventricular volume in coronary artery disease. PMID:3935147

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

    SciTech Connect

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

    1986-01-01

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

  11. Optimal value of filling pressure in the right side of the heart in acute right ventricular infarction.

    PubMed Central

    Berisha, S; Kastrati, A; Goda, A; Popa, Y

    1990-01-01

    Haemodynamic monitoring was performed within the first 48 hours after the onset of symptoms in basal conditions, during volume loading, and during infusion of glyceryl trinitrate in 41 patients who fulfilled the diagnostic electrocardiographic and haemodynamic criteria of right ventricular infarction. In most patients an increase of mean right atrial pressure up to 10-14 mm Hg was followed by an increase in right ventricular stroke work index. But raising the mean right atrial pressure above 14 mm Hg was almost always accompanied by a reduction in right ventricular stroke work index. When the mean right atrial pressure was reduced by intravenous glyceryl trinitrate to less than 14 mm Hg the right ventricular stroke index increased. The same response was seen with cardiac and stroke index. The mean (SD) values of optimal right atrial and pulmonary capillary pressures were 11.7 (2.1) and 16.5 (2.7) mm Hg respectively. Thus cardiac and stroke index increased and the right ventricle reached its maximum stroke work index when the filling pressure was 10-14 mm Hg. These values may be regarded as the optimal level of right ventricular filling pressure in patients with right ventricular infarction. PMID:2107863

  12. Endothelial function and chronic exposure to air pollution in normal male subjects.

    PubMed

    Briet, Marie; Collin, Cédric; Laurent, Stéphane; Tan, Alice; Azizi, Michel; Agharazii, Mohsen; Jeunemaitre, Xavier; Alhenc-Gelas, François; Boutouyrie, Pierre

    2007-11-01

    Exposure to urban air pollution, ultrafine particles or gases, is associated with acute cardiovascular mortality and morbidity. We investigated the effect of ambient air pollution on endothelial function in 40 healthy white male nonsmokers spontaneously breathing ambient air in Paris, France. Air pollutant levels (nitrogen, sulfur and carbon oxides, and particulate matter) were averaged during the 5 days preceding arterial measurements. Brachial artery endothelium-dependent flow-mediated dilatation and reactive hyperemia induced by hand ischemia and endothelium-independent glyceryl trinitrate dilatation were measured using a radiofrequency-based echo-tracking device at 2-week intervals. Flow-mediated dilatation was independently and negatively correlated with the average levels of sulfur dioxide (P<0.001) and nitrogen monoxide (P<0.01). Sulfur dioxide levels explained 19% of the variance of flow-mediated dilatation. An increase in gaseous pollutants, 2 weeks apart, was significantly associated with a decreased in flow-mediated dilatation. No association was found between air pollutants and glyceryl trinitrate-induced vasodilatation. Reactive hyperemia was significantly and positively correlated with particulate matter with aerodynamic diameters <10 microm and <2.5 microm (P<0.0001 and P<0.001, respectively) and nitrogen dioxide (P<0.01). An increase in particulate matter, 2 weeks apart, was significantly correlated with an increase in reactive hyperemia. Endothelial function was impaired by ordinary levels of pollution in healthy young males, in an urban area, and may be reduced by 50% between the least and the most polluted day. Gaseous pollutants affect large artery endothelial function, whereas particulate matter exaggerates the dilatory response of small arteries to ischemia. PMID:17875820

  13. Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction.

    PubMed Central

    Senior, R.; Glenville, B.; Basu, S.; Sridhara, B. S.; Anagnostou, E.; Stanbridge, R.; Edmondson, S. J.; Handler, C. E.; Raftery, E. B.; Lahiri, A.

    1995-01-01

    OBJECTIVES--To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS--45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS--Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS--Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction. Images PMID:7488446

  14. Acute and chronic arterial and venous effects of captopril in congestive cardiac failure.

    PubMed Central

    Capewell, S.; Taverner, D.; Hannan, W. J.; Muir, A. L.

    1989-01-01

    OBJECTIVE--To determine whether captopril alters peripheral venous tone in patients with congestive cardiac failure. DESIGN--Open study of patients at start of captopril treatment and three months later. SETTING--A hospital gamma camera laboratory. PATIENTS--16 Men with congestive cardiac failure in New York Heart Association class II or III, aged 57-73. INTERVENTIONS--Patients were initially given 500 micrograms sublingual glyceryl trinitrate followed by 25 mg oral captopril. The study was then repeated after three months' captopril treatment. MAIN OUTCOME MEASURES--Previously validated non-invasive radionuclide techniques were used to measure changes in central haemodynamic variables and peripheral venous volumes in the calf. RESULTS--After 25 mg captopril there were falls in blood pressure and relative systemic vascular resistance and increases in cardiac index and left ventricular ejection fraction. This was accompanied by a 16% increase in peripheral venous volume (95% confidence interval 13.4% to 18.4%, p less than 0.01), which compared with an 11% increase after 500 micrograms glyceryl trinitrate (10% to 12%, p less than 0.01). Eleven patients were restudied after three months' continuous treatment with captopril. The resting venous volume was higher than it had been initially, by about 10%, and increased by a further 8.4% after 25 mg captopril (5.4% to 11.4%, p less than 0.05). CONCLUSIONS--Captopril is an important venodilator. Venous and arterial dilatation are produced short term and during long term treatment. PMID:2508945

  15. Assessment of left ventricular function in coronary artery disease with the nuclear probe during intervention studies.

    PubMed Central

    Lahiri, A; Bowles, M J; Jones, R I; Crawley, J C; Raftery, E B

    1984-01-01

    The nuclear probe was used for measuring left ventricular function in 11 normal subjects and the results compared with those using a digital gammacamera. The probe was then used to measure left ventricular function in patients with coronary artery disease during dynamic exercise and stress atrial pacing. The ability of the probe to detect changes induced by glyceryl trinitrate was also evaluated in separate parallel studies. In the 11 normal subjects there was a good correlation between the left ventricular ejection fraction measured by the gammacamera and the nuclear probe both at rest and during exercise. Exercise increased this value by at least 5% in all normal subjects during measurements with both the gammacamera and the nuclear probe. The mean (SD) difference was -0.3% (2.60) at rest and 2.3% (5.02) at peak exercise. Both exercise and pacing produced angina in the patient group and the mean (SEM) value fell from 52% (3.5) to 28% (2.6) and from 46% (5.1) to 34% (3.2) respectively. Glyceryl trinitrate prolonged the exercise and pacing times, and the corresponding falls in ejection fraction were significantly reduced. The non-imaging nuclear probe is a cheap and portable instrument capable of assessing left ventricular function in patients with cardiac disease. It is designed for high count rate acquisition over a short period of time and can thus provide both beat to beat and summated left ventricular time activity curves suitable for quantitative analysis. It therefore has important advantages in the clinical setting and during controlled interventions compared with the gammacameras. PMID:6433946

  16. Slow release nifedipine plus atenolol in chronic stable angina pectoris.

    PubMed Central

    Challenor, V F; Waller, D G; Renwick, A G; George, C F

    1989-01-01

    1. The effects of adding slow release nifedipine in doses of 20 mg and 40 mg twice daily to atenolol therapy (50 mg twice daily) were assessed in 18 patients with chronic stable angina. 2. The addition of the lower dose of nifedipine to atenolol did not significantly alter the weekly consumption of glyceryl trinitrate or the mean number of anginal attacks as assessed by diary cards. However, 2 h after dosing there was a significant prolongation during stress testing in the time to onset of both 1 mm ST depression on the ECG (by 28%) and to angina (by 37%) compared with atenolol alone, but no benefit was apparent by 12 h after dosing. 3. At a dose of 40 mg twice daily, nifedipine significantly reduced glyceryl trinitrate consumption by 25% and the number of anginal attacks by 36%. The times to onset of ST depression and angina were increased by 37% and 55% respectively at 2 h and by 24% and 26% respectively 12 h after dosing. 4. Analysis of the frequency distribution of anginal attacks showed decreasing efficacy with time after administration of nifedipine. The overall results also suggest a relationship between efficacy and the plasma nifedipine concentration, with a mean 20% improvement in time to development of angina occurring at a nifedipine plasma concentration of approximately 30-40 ng ml-1. 5. In conclusion, the reduction of effort-related angina by nifedipine is related to its plasma concentration and the effective duration of action of the 20 mg slow release formulation is less than 12 h. PMID:2511911

  17. Complex stenosis morphology and vasomotor responses to inhibition of nitric oxide synthesis

    PubMed Central

    Tousoulis, D; Tentolouris, C; Crake, T; Goumas, G; Stefanadis, C; Toutouzas, P; Davies, G

    2000-01-01

    OBJECTIVE—To assess the relation between coronary vasomotor effects of NG-monomethyl-L-arginine (LNMMA) administration and coronary stenosis morphology, length, and severity in patients with stable angina.
DESIGN—In 28 patients (24 male, four female) with coronary artery disease and chronic stable angina, intracoronary normal saline and 4 µmol/min LNMMA were infused for four minutes each, followed by an intracoronary bolus of 250 µg glyceryl trinitrate. Coronary stenoses were classified as concentric (smooth), eccentric (smooth), or complicated (irregular). The diameters of these stenoses and their adjacent reference proximal segments were measured by quantitative angiography.
RESULTS—During LNMMA infusion a significantly larger proportion of complicated stenoses than concentric and eccentric stenoses constricted by ⩾ 5% (p < 0.01) and the magnitude of vasoconstriction was greater in complicated than in concentric and eccentric stenoses (p < 0.05). For complicated stenoses the magnitude of constriction (in mm) with reference to normal saline was greater than that of the concentric and eccentric stenoses (p < 0.05), whereas concentric and eccentric stenoses constricted similarly. Irrespective of the type of morphology, there was a correlation (p < 0.05) between both the severity and the length of stenoses and the magnitude of vasoconstriction to LNMMA. A similar proportion of concentric, eccentric, and complicated stenoses showed ⩾ 5% increase in diameter with glyceryl trinitrate, and the magnitude of the response was similar in the three groups.
CONCLUSIONS—In patients with coronary artery disease, the response to LNMMA is greater when stenosis morphology is complex, indicating greater nitric oxide activity. This provides further evidence that plaques with complex morphology are in an active state.


Keywords: endothelium; nitric oxide; coronary artery disease; stenosis morphology PMID:11040015

  18. Effect of drug solubility and different excipients on floating behaviour and release from glyceryl monooleate matrices.

    PubMed

    Kumar M, Kiran; Shah, Manish H; Ketkar, Anant; Mahadik, K R; Paradkar, Anant

    2004-03-19

    Glycerol monooleate (GMO) matrix was found to be a gastro-retentive carrier system suitable for both polar and as well as non-polar drugs. Chlorpheniramine maleate (CPM) and diazepam (DZP) were used as model drugs. Effect of PEG 4000, PEG 10000, and stearic acid on floatability and release profile was studied. Water uptake increased with increase in the loading of polar drug (CPM) and decreased with non-polar drug (DZP). Similar effect was found to occur in case of drug release. PEGs increased the release up to certain concentration and decreased thereafter. Drug release decreased linearly with concentration of stearic acid. The type and extent of mesophases formed were significantly affected by the nature of drug, excipients and their concentration. Thus the selection of suitable excipients depending on polarity of drug, could help to modulate the floatability and release profile from GMO matrices. PMID:15019078

  19. 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. PMID:26276253

  20. Surface components of chylomicrons from rats fed glyceryl or alkyl esters of fatty acids: minor components.

    PubMed

    Yang, L Y; Kuksis, A; Myher, J J; Pang, H

    1992-08-01

    The lipid class, fatty acid and molecular species composition of the minor polar surface components of rat lymph chylomicrons were determined during absorption of menhaden oil and corn oil or of the corresponding fatty acid ethyl esters. In addition to the previously reported minor polar lipids (sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidic acid and lysophosphatidylcholine), we identified phosphatidylglycerol, dimethylphosphatidylethanolamine, ceramide and cholesteryl sulfate in the chylomicrons from both oil and ester feeding. The dietary fatty acids were found to be incorporated to a variable extent into the different phospholipid classes, the proportions of which remained the same during both types of feeding. No evidence was obtained for the presence of the minor glycerophospholipids characteristic of the lysosomal membranes (e.g., bis-phosphatidic, lysobisphosphatidic and semilysobis-phosphatidic acids), although special efforts were made to identify them. These results indicate that the chylomicrons arising from the monoacylglycerol and phosphatidic acid pathways of triacylglycerol biosynthesis become enveloped in closely similar monolayers of phospholipids. Hence, all triacylglycerols may be secreted from the villus cells via a common mechanism as suggested by the previously demonstrated convergence (at the 2-monoacylglycerol stage) of the monoacylglycerol and the phosphatidic acid pathways of mucosal triacylglycerol formation [Yang, Y.L., and Kuksis, A. (1991) J. Lipid Res. 32, 1173-1186]. PMID:1406072

  1. 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

  2. Glycerophosphocholine Metabolism in Higher Plant Cells. Evidence of a New Glyceryl-Phosphodiester Phosphodiesterase

    PubMed Central

    van der Rest, Benoît; Boisson, Anne-Marie; Gout, Elisabeth; Bligny, Richard; Douce, Roland

    2002-01-01

    Glycerophosphocholine (GroPCho) is a diester that accumulates in different physiological processes leading to phospholipid remodeling. However, very little is known about its metabolism in higher plant cells. 31P-Nuclear magnetic resonance spectroscopy and biochemical analyses performed on carrot (Daucus carota) cells fed with GroPCho revealed the existence of an extracellular GroPCho phosphodiesterase. This enzymatic activity splits GroPCho into sn-glycerol-3-phosphate and free choline. In vivo, sn-glycerol-3-phosphate is further hydrolyzed into glycerol and inorganic phosphate by acid phosphatase. We visualized the incorporation and the compartmentation of choline and observed that the major choline pool was phosphorylated and accumulated in the cytosol, whereas a minor fraction was incorporated in the vacuole as free choline. Isolation of plasma membranes, culture medium, and cell wall proteins enabled us to localize this phosphodiesterase activity on the cell wall. We also report the existence of an intracellular glycerophosphodiesterase. This second activity is localized in the vacuole and hydrolyzes GroPCho in a similar fashion to the cell wall phosphodiesterase. Both extra- and intracellular phosphodiesterases are widespread among different plant species and are often enhanced during phosphate deprivation. Finally, competition experiments on the extracellular phosphodiesterase suggested a specificity for glycerophosphodiesters (apparent Km of 50 μm), which distinguishes it from other phosphodiesterases previously described in the literature. PMID:12226504

  3. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... esters of fatty acids (the lactic acid esters of mono- and diglycerides) may be safely used in food in accordance with the following prescribed conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty...

  4. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... esters of fatty acids (the lactic acid esters of mono- and diglycerides) may be safely used in food in accordance with the following prescribed conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty...

  5. 21 CFR 172.852 - Glyceryl-lacto esters of fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... esters of fatty acids (the lactic acid esters of mono- and diglycerides) may be safely used in food in accordance with the following prescribed conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... esters of fatty acids (the lactic acid esters of mono- and diglycerides) may be safely used in food in accordance with the following prescribed conditions: (a) They are manufactured from glycerin, lactic acid, and fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty...

  7. [Quantitative gas chromatography-mass spectrometry determination of pentaerythrityl tetranitrate metabolites pentaerythrityl trinitrate, pentaerythrityl dinitrate and pentaerythrityl in human plasma].

    PubMed

    Schütz, A; Kötting, J; Epple, F; Ziegler, R; Maier-Lenz, H; Stalleicken, D

    1999-11-01

    Assay methods based on gas chromatography/mass spectroscopy (GC-MS) may be used to measure PE1N (pentaerithrityl mononitrate, CAS 1607-00-7), PE2N (pentaerithrityl dinitrate, CAS 1607-01-8) and intermediate pentaerithrityltrinitrate (PE3N, CAS 1607-17-6) in human plasma. Based on this method a simplified method to quantify the metabolites of PETN (pentaerithrityl tetranitrate, CAS 78-11-5, Pentalong) is described. In the present study a consistent method to extract the metabolites of human plasma and following derivatisation is described. Since PE1N can be quantified up to 150 ng/ml, PE2N and PE3N up to 30 ng/ml in human plasma, a dilution of the plasma samples can be avoided. The mean recovery rate is not so high as in other described methods, and inaccuracy is about 10%. Therefore a calibration range between 0.2-30 ng/ml of PE2N and 1-150 ng/ml of PE1N has to be considered. The described method offers an alternative and applicable option to quantify the PETN-metabolites and elucidate their part as NO-donors. PMID:10604040

  8. Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide.

    PubMed

    Banoujaafar, Hayat; Monnier, Alice; Pernet, Nicolas; Quirié, Aurore; Garnier, Philippe; Prigent-Tessier, Anne; Marie, Christine

    2016-09-01

    Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium-derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p-eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n = 6), physical exercise (n = 6) or a combination of both (n = 6) as experimental approaches to modulate flow-induced NO production by the cerebrovasculature. Tropomyosin-related kinase type B (TrkB) receptors and its phosphorylated form at tyrosine 816 (p-TrkB) were also measured. Moreover, we investigated BDNF synthesis in brain slices exposed to the NO donor glyceryl trinitrate. Our results showed increased p-eNOS and BDNF levels after exercise and decreased levels after vascular occlusion as compared to corresponding controls, with a positive correlation between changes in p-eNOS and BDNF (r = 0.679). Exercise after vascular occlusion did not change levels of these proteins. Gyceryl trinitrate increased proBDNF and BDNF levels in brain slices, thus suggesting a possible causal relationship between NO and BDNF. Moreover, vascular occlusion, like exercise, resulted in increased TrkB and p-TrkB levels, whereas no change was observed with the combination of both. These results suggest that brain BDNF signaling may be dependent on cerebral endothelium-derived NO production. PMID:27306299

  9. 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.

  10. 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. PMID:24262092

  11. A comparison of the cyclooxygenase inhibitor-NO donors (CINOD), NMI-1182 and AZD3582, using in vitro biochemical and pharmacological methods.

    PubMed

    Young, Delano V; Cochran, Edward D; Dhawan, Vijay; Earl, Richard A; Ellis, James L; Garvey, David S; Janero, David R; Khanapure, Subhash P; Letts, L Gordon; Melim, Terry L; Murty, Madhavi G; Shumway, Matthew J; Wey, Shiow-Jyi; Zemtseva, Irina S; Selig, William M

    2005-11-01

    Cyclooxygenase (COX, EC 1.14.99.1) inhibitor-nitric oxide (NO) donor (CINOD) hybrid compounds represent an attractive alternative to NSAID and coxib therapy. This report compares two CINODs, NMI-1182 (naproxen-glyceryl dinitrate) and AZD3582 (naproxen-n-butyl nitrate), for their ability to inhibit COX-1 and -2, deliver bioavailable nitric oxide, and release naproxen, using in vitro biochemical and pharmacological methods. In human whole blood, both CINODs showed inhibition, comparable to naproxen, of both COX isozymes and slowly released naproxen. Both CINODs donated bioavailable NO, as detected by cGMP induction in the pig kidney transformed cell line, LLC-PK1, but NMI-1182 was more potent by 30-100 times than AZD3582, GTN, GDN, and ISDN and considerably faster in inducing cGMP synthesis than AZD3582. The nitrate groups of GTN, NMI-1182, and AZD3582 appeared to be bioactivated via a common pathway, since each compound desensitized LLC-PK1 cells to subsequent challenge with the other compounds. Similar cGMP induction also occurred in normal, untransformed cells (human renal proximal tubule epithelial cells and hepatocytes from man, rat, and monkey); again, NMI-1182 was superior to AZD3582. NMI-1182 was also the more metabolically labile compound, releasing more absolute nitrate and nitrite (total NO(x)) in human stomach (in which NO is salutary) and liver S9 homogenates. Naproxen was also more rapidly freed from NMI-1182 than AZD3582 in human stomach, although liver S9 hydrolyzed both CINODs with similar rates. These in vitro tests revealed that NMI-1182 may be a better CINOD than AZD3582 because of its superior NO donating and naproxen liberating properties. PMID:16168964

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

    PubMed

    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

  13. Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia

    PubMed Central

    Cotechini, Tiziana; Komisarenko, Maria; Sperou, Arissa; Macdonald-Goodfellow, Shannyn; Adams, Michael A.

    2014-01-01

    Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5–16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications. PMID:24395887

  14. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

    SciTech Connect

    Ignarro, L.J.; Buga, G.M.; Wood, K.S.; Byrns, R.E.; Chaudhuri, G.

    1987-12-01

    The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is and unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. The authors have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were compared with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. Thus, EDRF released from artery and vein possesses identical and biological and chemical properties as NO.

  15. Vascular system: role of nitric oxide in cardiovascular diseases.

    PubMed

    Bian, Ka; Doursout, Marie-Françoise; Murad, Ferid

    2008-04-01

    In contrast with the short research history of the enzymatic synthesis of nitric oxide (NO), the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin) is the first compound of this category. On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning NO as a signaling molecule in the cardiovascular system. NO-mediated signaling is a recognized component in various physiologic processes (eg, smooth muscle relaxation, inhibition of platelet and leukocyte aggregation, attenuation of vascular smooth muscle cell proliferation, neurotransmission, and immune defense), to name only a few. NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Some of these processes (eg, smooth muscle relaxation, platelet aggregation, and neurotransmission) require only a brief production of NO at low nanomolar concentrations and are dependent on the recruitment of cyclic guanosine monophosphate (cGMP)-dependent signaling. Other processes are associated with direct interaction of NO or reactive nitrogen species derived from it with target proteins and requires a more sustained production of NO at higher concentrations but do not involve the cGMP pathway. PMID:18401228

  16. 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. PMID:24596995

  17. 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

  18. Reaction of organic nitrate esters and S-nitrosothiols with reduced flavins: a possible mechanism of bioactivation.

    PubMed

    Wong, P S; Fukuto, J M

    1999-04-01

    Organic nitrate esters, such as glyceryl trinitrate and isosorbide dinitrate, are a class of compounds used to treat a variety of vascular ailments. Their effectiveness relies on their ability to be bioactivated to nitric oxide (NO) which, in turn, relaxes vascular smooth muscle. Although there have been many biological studies that indicate that NO can be formed from organic nitrate esters in a biological environment, the chemical mechanism by which this occurs has yet to be established. Previous studies have implicated both flavins and thiols in organic nitrate ester bioactivation. Thus, we examined the chemical interactions of flavins and thiols with organic nitrate esters as a means of determining the role these species may play in NO production. Based on these studies we concluded that a reasonable chemical mechanism for organic nitrate ester bioactivation involves reduction to the organic nitrite ester followed by conversion to a nitrosothiol. The release of NO from nitrosothiols can occur via a variety of processes including reaction with dihydroflavins and NADH. PMID:10232931

  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. Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

    PubMed Central

    Bridges, A B; McLaren, M; Scott, N A; Pringle, T H; McNeill, G P; Belch, J J

    1993-01-01

    OBJECTIVES--To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN--Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS--Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS--There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION--Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning. PMID:8435236

  1. A fluorescence anisotropy study of stabilizing effect of tri- and tetra- nitrovasodilatory drugs on DPPC liposomal membrane.

    PubMed

    Ghosh, A K; Mukherjee, J; Basu, R; Chatterjee, M; Nandy, P

    1993-11-21

    Glyceryl trinitrate (GT) and pentaerythritol tetranitrate (PT) are two vasodilatory drugs. The physical properties of the membrane lipid matrix, which determine the structure and function of the membrane-bound proteins, generally control the perturbation mechanism of these drugs. Thus, physical interaction of these drugs with membrane lipids is very crucial for their clinical use, different cellular processes, as well as for targetted drug delivery systems. In the present paper, we have reported for the first time the interaction between these drugs and the lipid molecules in the liposomal system of dipalmitoylphosphatidyl-choline (DPPC), as measured by steady-state fluorescence anisotropy using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescent probe. Our results show that by dissolving in the lipid matrix these two drugs effectively stabilise the liposomal membrane: the effect being more in case of GT than in PT, indicating that the rigidifying effect is independent of the number of nitrate groups of the two drugs. This effect increases with the increase in drug concentration, implying solubilisation of all drug molecules. Though our in vitro study has more physical significance than a physiological one, the results obtained here may be used to interpret the effects that are observed in vivo. PMID:8241246

  2. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

    SciTech Connect

    MacNaughton, W.K.; Wallace, J.L. ); Cirino, G. )

    1989-01-01

    The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protective effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.

  3. 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.

  4. Mechanism of shock associated with right ventricular infarction.

    PubMed Central

    Creamer, J E; Edwards, J D; Nightingale, P

    1991-01-01

    Various mechanisms have been proposed to explain the shock sometimes associated with right ventricular infarction, but only small numbers of patients with clinical shock have been studied. The haemodynamic profiles of seven patients with clinical cardiogenic shock after right ventricular myocardial infarction were studied prospectively. They were selected because all had a stable cardiac rhythm and none had absolute hypovolaemia during the study period. In all of them the mean right atrial pressure exceeded the pulmonary artery occlusion pressure. After treatment with varying combinations of dopamine, dobutamine, and glyceryl trinitrate (titrated to achieve the optimum haemodynamic response) the mean systemic arterial pressure increased, as did the cardiac index. There was an associated increase in the left ventricular stroke work index but the right ventricular stroke work index was unchanged. There was no significant change in heart rate, mean right atrial pressure, or pulmonary artery occlusion pressure. This suggests that the probable mechanism of the shock associated with right ventricular infarction is concomitant severe left ventricular dysfunction. PMID:1867948

  5. 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. PMID:26870462

  6. Role of the lipid peroxidation product, 4-hydroxynonenal, in the development of nitrate tolerance.

    PubMed

    D'Souza, Yohan; Kawamoto, Toshihiro; Bennett, Brian M

    2014-04-21

    Tolerance to nitrates such as nitroglycerin (GTN) is associated with oxidative stress, inactivation of aldehyde dehydrogenase 2 (ALDH2), and decreased GTN-induced cGMP accumulation and vasodilation. We hypothesized that GTN-induced inactivation of ALDH2 results in increased 4-hydroxy-2-nonenal (HNE) adduct formation of key proteins involved in GTN bioactivation, and, consequently, an attenuated vasodilator response to GTN (i.e., tolerance). We used an in vivo GTN tolerance model, a cell culture model of nitrate action, and Aldh2(-/-) mice to assess whether GTN exposure resulted in HNE adduct formation, and whether exogenous HNE affected GTN-induced relaxation and cGMP accumulation. Immunoblot analysis indicated a marked increase in HNE adduct formation in GTN-tolerant porcine kidney epithelial cells (PK1) and in aortae from GTN-tolerant rats and untreated Aldh2(-/-) mice. Preincubation of PK1 cells with HNE resulted in a dose-dependent decrease in GTN-induced cGMP accumulation, and pretreatment of isolated rat aorta with HNE resulted in dose-dependent decreases in the vasodilator response to GTN, thus mimicking GTN-tolerance. Pretreatment of aortae from Aldh2(-/-) mice with 10 μM HNE resulted in a desensitized vasodilator response to GTN. In the in vivo rat tolerance model, changes in HNE adduct formation correlated well with the onset of GTN tolerance and tolerance reversal. Furthermore, coadministration of an HNE scavenger during the tolerance induction protocol completely prevented HNE adduct formation and GTN tolerance but did not prevent the inactivation of ALDH2. The data are consistent with a novel mechanism of GTN tolerance suggesting a primary role of HNE adduct formation in the development of GTN tolerance. PMID:24555687

  7. Cortical NADH during pharmacological manipulations of the respiratory chain and spreading depression in vivo.

    PubMed

    Rex, A; Pfeifer, L; Fink, F; Fink, H

    1999-08-01

    The nicotinamide adenine dinucleotide (NADH) is one of the main means for energy transfer in the mitochondrial respiratory chain and is an important parameter of cellular metabolism. NADH can be measured by its fluorescence and various fluorometric methods have been developed. In this study, a pulsed nitrogen laser combined with a fibreoptic set-up and photomultipliers was used to induce and measure NADH fluorescence on the cortical surface. The aim of the study was to assess the suitability of the laser induced spectroscopy for in vivo and on-line measurement of NADH in neuroscience and particularly for the assessment of neuronal metabolism. Changes in cerebral blood flow may affect fluorescence measurement. To assess the consequences of alterations in blood flow, the vasodilators glyceryl trinitrate and nimodipine and the vasoconstrictor endothelin-1 were applied. The induced hemodynamic changes were verified by colour Doppler sonography. The tests using the vasodilators showed that an increased blood flow in the brain increased not only NADH fluorescence but also the scattered light measured. The vasoconstrictor caused opposite effects. Insertion of a compensation method (subtraction of the scattered light) allowed the exclusion of hemodynamic artifacts. Effects of changes in the cellular metabolism were induced by sodium cyanide, an inhibitor of the mitochondrial respiratory chain, or by 2,4-dinitrophenol (2,4-DNP), an uncoupler of the oxidative phosphorylation. Sodium cyanide induced a transient increase of NADH fluorescence and 2,4-DNP decreased intracellular NADH fluorescence. Furthermore, the repercussions of cortical spreading depressions (CSD), a response of the brain to noxious stimuli, on cortical NADH fluorescence were determined. A single CSD decreased cortical NADH fluorescence for about 1 min, followed by a 5- to 10-min increase. The changes in NADH levels seem to correspond with the excitation and inhibition of neuronal metabolism, respectively. In

  8. Efficacy of folic acid supplementation on endothelial function and plasma homocysteine concentration in coronary artery disease: A meta-analysis of randomized controlled trials

    PubMed Central

    YI, XIN; ZHOU, YANLI; JIANG, DINGSHENG; LI, XIAOYAN; GUO, YI; JIANG, XUEJUN

    2014-01-01

    The aim of the present study was to conduct an updated meta-analysis of relevant randomized controlled trials (RCTs) in order to estimate the effect of folic acid supplementation on endothelial function and the concentration of plasma homocysteine in patients with coronary artery disease (CAD). An extensive search of PubMed was conducted to identify RCTs that compared folic acid with placebo therapy. The mean difference (MD) and 95% confidence interval (CI) were used as a measure of the correlation between folic acid supplementation and endothelial function/plasma homocysteine concentration. Of the 377 patients included in this analysis, 191 patients underwent folic acid supplementation and 186 individuals underwent placebo treatment. Compared with the use of a placebo, folic acid supplementation alone exhibited significant efficacy on increasing flow-mediated dilation (FMD; MD, 57.72 μm; 95% CI, 50.14–65.31; P<0.05) and lowering the concentration of plasma homocysteine (MD, −3.66 μmol/l; 95% CI, −5.44–−1.87; P<0.05; I2, 87%). There was no significant change in the response to end diastolic diameter, glyceryl-trinitrate diameter, heart rate, baseline and peak hyperemic flow and systolic and diastolic blood pressure between the folic acid and placebo groups (P>0.05). Therefore, the meta-analysis indicated that 5 mg folic acid daily supplementation for >4 weeks significantly improved FMD and lowered the concentration of plasma homocysteine in patients with CAD. However, more RCTs are required in order to confirm these observations. PMID:24940394

  9. Direct and reflex effects of nitroglycerin on coronary and left ventricular dynamics in conscious dogs

    PubMed Central

    Vatner, Stephen F.; Higgins, Charles B.; Millard, Ronald W.; Franklin, Dean

    1972-01-01

    The effects of intravenous and sublingual glyceryl trinitrate (nitroglycerin), 40 μg/kg, were studied on coronary blood flow and resistance, left ventricular (LV) pressures (P) and diameters (D), rate of change of pressure (dP/dt), (dP/dt)/P, and on the velocity (V) of myocardial fiber shortening in conscious dogs. Nitroglycerin i.v. caused substantial coronary vasodilatation prior to any changes in systemic hemodynamics. Mean coronary flow increased by a maximum of 47 ml/min and coronary sinus Po2 rose from 16 to 26 mm Hg while pressure and diameter began to fall, and heart rate began to rise. After the maximal fall in mean arterial pressure (—26 mm Hg), a secondary peak in coronary flow occurred which was associated with increases in heart rate (100 beats/min), (dP/dt)/P (22%), and isolength V (12%). Beta blockade prevented the reflex increases in contractility but only a part of the reflex tachycardia; the remainder was prevented by cholinergic blockade. Maintaining heart rate constant minimized the decreases in LV D and increases in contractility. When the reflex inotropic and chronotropic effects were prevented by a combination of atrial pacing and beta blockade the early coronary vasodilatation was unaltered, but the later coronary vasodilatation was minimized. Thus i.v. nitroglycerin in the conscious dog exerts a potent direct coronary vasodilating action and also a secondary coronary vasodilation caused by reflex increases in contractility and heart rate. The decreases in diameter are largely the result of tachycardia. Sublingual nitroglycerin produced directionally similar, but quantitatively lesser effects on coronary flow and resistance, LV D, LV P, and contractility. Images PMID:4404139

  10. 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

  11. 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. PMID:23374622

  12. 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

  13. Relaxant mechanisms of 3, 5, 7, 3', 4'-pentamethoxyflavone on isolated human cavernosum.

    PubMed

    Jansakul, Chaweewan; Tachanaparuksa, Kuldej; Mulvany, Michael J; Sukpondma, Youwapa

    2012-09-15

    We have investigated effects and mechanisms responsible for the activity of 3, 5, 7, 3', 4'-pentamethoxyflavone (PMF) on isolated human cavernosum. PMF is the major flavone isolated from Kaempferia parviflora claimed to act as an aphrodisiac. PMF caused relaxation of phenylephrine precontracted human cavernosal strips, and this effect was slightly inhibited by N(G)-nitro-l-arginine, a nitric oxide synthase inhibitor, but not by ODQ (soluble guanylate cyclase inhibitor), TEA (tetraethylammonium, blocker of voltage-dependent K(+) channels) or glybenclamide (blocker of ATP-dependent K(+) channels). PMF did not significantly inhibit the relaxant activity of glyceryltrinitrate or acetylcholine on human cavernosal strips precontracted with phenylephrine. In contrast, sildenafil (phosphodiesterase inhibitor) potentiated the relaxant activity of glyceryl trinitrate but not of acetylcholine. In normal Krebs solution with nifedipine (blocker of l-type Ca(2+) channels), or in Ca(2+)-free Krebs solution, PMF caused a further inhibition of human cavernosum contracted with phenylephrine. In human cavernosum treated with thapsigargin (inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase) in Ca(2+)-free medium, PMF suppressed the concentration-response curve of human cavernosum to phenylephrine and a further suppression was found when SKF-96365 (a blocker of store-operated Ca(2+) channels and Y-27632 (inhibitor of Rho-kinase)), but not nifedipine, were added sequentially. Thus, PMF had only a weak effect on the release of nitric oxide, and had no effect as a K(ATP)- or K(Ca) channel opener, a phosphodiesterase inhibitor, a store-operated Ca(2+) channel blocker or a Rho-kinase inhibitor. Therefore, these studies suggest that PMF causes relaxation of human cavernosum through voltage-dependent Ca(2+) channels and other mechanisms associated with calcium mobilization. PMID:22800934

  14. The association between functional and morphological assessments of endothelial function in patients with rheumatoid arthritis: a cross-sectional study

    PubMed Central

    2013-01-01

    Introduction Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). One of the earliest manifestations of CVD is endothelial dysfunction (ED), which can lead to functional and morphological vascular abnormalities. Several non-invasive assessments of vascular function and morphology can be utilised to assess vascular health, but little is known about the association between each of these assessments in patients with RA, and they tend to be used interchangeably in the literature. The objective of the present study was to examine associations between measures of vascular function and morphology in patients with RA. Methods A total of 201 RA patients (155 females, median (25th to 75th percentile) age: 67 (59 to 73)) underwent assessments of microvascular endothelium-dependent and endothelium-independent function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside respectively), macrovascular endothelium-dependent and endothelium-independent function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilation respectively), and vascular morphology (pulse wave analysis, carotid intima-media thickness (cIMT), and carotid plaque). Results Spearman's correlations revealed that from the functional parameters, only macrovascular endothelium-independent function was inversely associated with cIMT (-0.294 (P < 0.001)) after applying the Bonferroni correction for multiple comparisons. For carotid plaque, t tests showed that macrovascular endothelium-independent function was lower in patients with plaque than without (15.5 ± 8.3 vs. 23.1 ± 9.1%, P = 0.002, respectively). Conclusions With the exception of macrovascular endothelium-independent function, all other measures of vascular function were not associated with vascular morphology. This suggests that different assessments of vascular function and morphology in patients with RA reflect quite distinct mechanisms and phases of the

  15. Lipoxygenase and cyclo-oxygenase products in the control of regional kidney blood flow in rabbits.

    PubMed

    Oliver, Jeremy J; Eppel, Gabriela A; Rajapakse, Niwanthi W; Evans, Roger G

    2003-11-01

    1. The aim of the present study was to examine the roles of cyclo-oxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonate signalling cascades in the control of regional kidney blood flow. 2. In pentobarbitone-anaesthetized rabbits treated with NG-nitro-l-arginine and glyceryl trinitrate to 'clamp' nitric oxide, we determined the effects of ibuprofen (a COX inhibitor) and esculetin (a LOX inhibitor) on resting systemic and renal haemodynamics and responses to renal arterial infusions of vasoconstrictors. 3. Ibuprofen increased mean arterial pressure (14 +/- 5%) and reduced medullary laser Doppler flux (MLDF; 26 +/- 6%) when administered with esculetin. A similar pattern of responses was observed when ibuprofen was given alone, although the reduction in MLDF was not statistically significant. Esculetin tended to increase renal blood flow (RBF; 16 +/- 7%) and MLDF (28 +/- 13%) when given alone, but not when combined with ibuprofen. 4. After vehicle, renal arterial infusions of noradrenaline, angiotensin II and endothelin-1 reduced RBF and cortical laser Doppler flux (CLDF), but not MLDF. In contrast, renal arterial [Phe2,Ile3,Orn8]-vasopressin reduced MLDF but not RBF or CLDF. Ibuprofen alone did not significantly affect these responses. Esculetin, when given alone, but not when combined with ibuprofen, enhanced noradrenaline-induced renal vasoconstriction. In contrast, esculetin did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin, angiotensin II or endothelin-1. 5. We conclude that COX products contribute to the maintenance of arterial pressure and renal medullary perfusion under 'nitric oxide clamp' conditions, but not to renal haemodynamic responses to the vasoconstrictors we tested. Lipoxygenase products may blunt noradrenaline-induced vasoconstriction, but our observations may, instead, reflect LOX-independent effects of esculetin. PMID:14678242

  16. Nebivolol increases arterial distensibility in vivo.

    PubMed

    McEniery, Carmel M; Schmitt, Matthias; Qasem, Ahmad; Webb, David J; Avolio, Alberto P; Wilkinson, Ian B; Cockcroft, John R

    2004-09-01

    Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. beta-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that beta-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a beta2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension. PMID:15262912

  17. 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. PMID:26370679

  18. Endothelial dysfunction in young patients with acute ST-elevation myocardial infarction.

    PubMed

    Chen, Shyh-Ming; Tsai, Tzu-Hsien; Hang, Chi-Ling; Yip, Hon-Kan; Fang, Chi-Yuan; Wu, Chiung-Jen; Guo, Gary Bih-Fang

    2011-01-01

    Endothelial dysfunction may be particularly important in the pathogenesis of young patients with acute myocardial infarction (AMI), because they have different clinical characteristics compared with older patients. We investigated endothelial function in relation to AMI in this young age group. From January 2005 to March 2008, 29 of 31 consecutive patients with acute ST-elevation myocardial infarction (STEMI) who were <40 years old and received direct percutaneous coronary intervention (PCI) were enrolled in the study. We compared the coronary risk factors and flow-mediated vasodilation (FMD) in the brachial artery between the acute STEMI patients and 29 age- and gender-matched controls that did not have AMI. Baseline brachial artery diameter and responses to glyceryl trinitrate were similar between the two groups. In contrast, FMD was significantly lower in the young acute STEMI group than in the control (3.47 ± 4.08 vs. 7.45 ± 4.67%, p = 0.001) and correlated with the Thrombolysis in Myocardial Infarction (TIMI) risk score. The impaired FMD in the acute STEMI group was independent of smoking, hyperlipidemia, hypertension, nitrate use, or body mass index. In multiple logistic regression analysis, only FMD and age, not traditional cardiovascular risk factors, were found to be significantly associated with acute STEMI (odds ratio = 0.75, 95% CI 0.63-0.90, p < 0.01). In conclusion, independent of conventional risk factors, severe endothelial dysfunction occurs in young acute STEMI patients and correlates with TIMI score. In addition to age, impaired FMD is the only significant factor associated with acute STEMI in this young population. PMID:20949355

  19. Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach.

    PubMed Central

    Desai, K M; Warner, T D; Bishop, A E; Polak, J M; Vane, J R

    1994-01-01

    1. Nitric oxide synthase (NOS) was localized in the guinea pig stomach by immunocytochemistry. In vitro experiments were carried out on the isolated stomach of the guinea pig to study any possible links between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in mediating relaxations induced by vagal stimulation. 2. NOS was localized to nerve cell bodies and nerve fibre varicosities of the myenteric plexus in wholemounts of the longitudinal muscle-myenteric plexus of the stomach fundus. The NOS-positive cells had a Dogiel type I morphology characteristic of motor neurones. 3. The cross-sections of the stomach wall showed NOS-positive neurones mainly in the myenteric plexus ganglia and NOS-positive nerve fibre varicosities in the circular muscle layer. 4. Relaxations induced by vagal stimulation were almost completely prevented by L-NAME with an IC50 value of 5.5 x 10(-6) M. This inhibition was reversed by L-arginine (2 mM). 5. VIP (100 nM) induced reproducible relaxations of the stomach. These were unaffected by tetrodotoxin (2 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). 6. Desensitization to the relaxant effect of VIP partially reduced relaxations induced by vagal stimulation, glyceryl trinitrate or sodium nitroprusside but not noradrenaline. 7. These results show that NO has a neuronal origin in the guinea pig stomach, and support NO, and not VIP, as the major neurotransmitter of vagally induced gastric relaxation in the guinea pig. Images Figure 1 Figure 2 PMID:7534182

  20. 77 FR 59608 - Gas Transmission Northwest LLC; Notice of Petition for Declaratory Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... Energy Regulatory Commission Gas Transmission Northwest LLC; Notice of Petition for Declaratory Order... Practice and Procedure, 18 CFR 385.207(a)(2)(2012), Gas Transmission Northwest LLC (GTN), filed a petition... forth and used in GTN's tariff does not mean that the natural gas GTN transports on its system must...

  1. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months. PMID:25118474

  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. Abnormalities of endothelial function in patients with predialysis renal failure

    PubMed Central

    Thambyrajah, J; Landray, M; McGlynn, F; Jones, H; Wheeler, D; Townend, J

    2000-01-01

    BACKGROUND—Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure.
OBJECTIVE—To examine the relation between predialysis renal failure and endothelial function.
DESIGN—Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease.
RESULTS—Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease.
CONCLUSIONS—Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without

  4. The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5.

    PubMed

    Wallis, R M

    1999-10-01

    Sildenafil (1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d]pyrimidin-5-yl) phenylsulphonyl]-4-methylpiperazine) has been shown to be an effective oral treatment for male erectile dysfunction. Sildenafil is a potent competitive inhibitor of PDE5 (IC50 3.5 nM) and is selective over PDE1 to 4 (80 to 19,000-fold) and retinal PDE6 (10-fold). Sildenafil enhanced cGMP accumulation driven with sodium nitroprusside in the corpus cavernosum of rabbits without affecting cAMP formulation. In the absence of nitric oxide drive, sildenafil had no functional effect on the human and rabbit isolated corpus cavernosum, but potently potentiated the relaxant effects of nitric oxide on these tissues. In the anaesthetised dog, sildenafil (ED50: 12 to 16 micrograms/kg i.v.) enhanced the increase in intracavernosal pressure induced by electrical stimulation of the pelvic nerve or intracavernosal injection of sodium nitroprusside in the absence of meaningful effects on blood pressure. Consistent with its mode of action, sildenafil potentiated the vasorelaxant effects of glyceryl trinitrate on rabbit isolated aortic rings. However, unlike milrinone, sildenafil had no inotropic effects on the dog isolated trabeculae carneae. Thus it is unlikely to have the deleterious effects on cardiac function associated with PDE3 inhibitors. As a consequence of inhibition of PDE6 in the retina, sildenafil (1 to 100 microM) altered the kinetics of the light response of the dog isolated retina. In the anaesthetised dog, sildenafil modified the a- and b-wave of the electroretinogram induced by a flash of blue light. These effects were proportional to plasma concentrations, were fully reversible and only occurred following plasma concentrations higher (approximately 30-fold) than those active on intracavernosal pressure. These studies have shown that sildenafil is a potent and selective inhibitor of PDE5. It enhances the effect of nitric oxide on the corpus cavernosum and has been shown

  5. Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate

    PubMed Central

    Homer, Kerry L; Wanstall, Janet C

    2002-01-01

    Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-{N-methyl-N-[6-(N-methylammoniohexyl)amino]}diazen-1-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and to investigate the possible role of activation of sarco-endoplasmic reticulum calcium-ATPase (SERCA), independent of soluble guanylate cyclase, using thapsigargin. MAHMA NONOate concentration-dependently inhibited sub-maximal aggregation responses to collagen (2–10 μg ml−1) and adenosine diphosphate (ADP; 2 μM) in platelet rich plasma. It was (i) more effective at inhibiting aggregation induced by collagen than by ADP, and (ii) less potent at inhibiting platelet aggregation than relaxing rat pulmonary artery. ODQ (10 μM) caused only a small shift (approximately half a log unit) in the concentration-response curve to MAHMA NONOate irrespective of the aggregating agent. The NO-independent activator of soluble guanylate cyclase, YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole; 1–100 μM), did not inhibit aggregation. The cGMP analogue, 8-pCPT-cGMP (8-(4-chlorophenylthio)guanosine 3′5′ cyclic monophosphate; 0.1–1 mM), caused minimal inhibition. On collagen-aggregated platelets responses to MAHMA NONOate (ODQ 10 μM present) were abolished by thapsigargin (200 nM). On ADP-aggregated platelets thapsigargin caused partial inhibition. Results with S-nitrosoglutathione (GSNO) resembled those with MAHMA NONOate. Glyceryl trinitrate and sodium nitroprusside were poor inhibitors of aggregation. Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ-resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA. PMID:12429580

  6. Clinical pharmacokinetics of vasodilators. Part II.

    PubMed

    Kirsten, R; Nelson, K; Kirsten, D; Heintz, B

    1998-07-01

    Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast

  7. Lesions in Guddesn's tegmental nuclei produce behavioral and 5-HT effects similar to those after raphe lesions.

    PubMed

    Lorens, S A; Köhler, C; Guldberg, H C

    1975-01-01

    Lesions largely restricted to the dorsal and ventral tegmental nuclei of Gudden (GTN) produced several effects similar to those seen after midbrain raphe lesions. GTN lesions significantly reduced the 5-hydroxytryptamine (5-HT) concentration of the diencephalon (31 percent), hippocampus (59 percent), and remaining portion of the telencephalon (29 percent). Striatal 5-HT, however, was not affected. GTN lesions enhanced activity in an enclosed field and facilitated two-way avoidance acquisition. Pain sensitivity as measured by the flinch-jump method was not affected. These results suggest that the GTN may be the origin of ascending 5-HT fides and may be involved in the regulation of activity level and the adaptation of an animal to aversive situations. Thus, some of the behavioral and 5-HT effects of lesions in the midbrain raphe nuclei may be due to their involvement of the GTN and associated pathways. PMID:1187729

  8. 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.

  9. Bioactivation of Nitroglycerin by Purified Mitochondrial and Cytosolic Aldehyde Dehydrogenases*

    PubMed Central

    Beretta, Matteo; Gruber, Karl; Kollau, Alexander; Russwurm, Michael; Koesling, Doris; Goessler, Walter; Keung, Wing Ming; Schmidt, Kurt; Mayer, Bernd

    2008-01-01

    Metabolism of nitroglycerin (GTN) to 1,2-glycerol dinitrate (GDN) and nitrite by mitochondrial aldehyde dehydrogenase (ALDH2) is essentially involved in GTN bioactivation resulting in cyclic GMP-mediated vascular relaxation. The link between nitrite formation and activation of soluble guanylate cyclase (sGC) is still unclear. To test the hypothesis that the ALDH2 reaction is sufficient for GTN bioactivation, we measured GTN-induced formation of cGMP by purified sGC in the presence of purified ALDH2 and used a Clark-type electrode to probe for nitric oxide (NO) formation. In addition, we studied whether GTN bioactivation is a specific feature of ALDH2 or is also catalyzed by the cytosolic isoform (ALDH1). Purified ALDH1 and ALDH2 metabolized GTN to 1,2- and 1,3-GDN with predominant formation of the 1,2-isomer that was inhibited by chloral hydrate (ALDH1 and ALDH2) and daidzin (ALDH2). GTN had no effect on sGC activity in the presence of bovine serum albumin but caused pronounced cGMP accumulation in the presence of ALDH1 or ALDH2. The effects of the ALDH isoforms were dependent on the amount of added protein and, like 1,2-GDN formation, were sensitive to ALDH inhibitors. GTN caused biphasic sGC activation with apparent EC50 values of 42 ± 2.9 and 3.1 ± 0.4 μm in the presence of ALDH1 and ALDH2, respectively. Incubation of ALDH1 or ALDH2 with GTN resulted in sustained, chloral hydrate-sensitive formation of NO. These data may explain the coupling of ALDH2-catalyzed GTN metabolism to sGC activation in vascular smooth muscle. PMID:18450747

  10. 5-HIAA

    MedlinePlus

    HIAA; 5-hydroxyindole acetic acid; Serotonin metabolite ... interfere with the test. Medicines that can increase 5-HIAA measurements include acetaminophen (Tylenol), acetanilide, phenacetin, glyceryl ...

  11. 21 CFR 582.60 - Synthetic flavoring substances and adjuvants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...). Geranyl acetate (geraniol acetate). Glycerol (glyceryl) tributyrate (tributyrin, butyrin). Limonene (d-, l... (benzoic aldehyde). N-Butyric acid (butanoic acid). d- or l-Carvone (carvol). Cinnamaldehyde...

  12. 21 CFR 582.60 - Synthetic flavoring substances and adjuvants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...). Geranyl acetate (geraniol acetate). Glycerol (glyceryl) tributyrate (tributyrin, butyrin). Limonene (d-, l... (benzoic aldehyde). N-Butyric acid (butanoic acid). d- or l-Carvone (carvol). Cinnamaldehyde...

  13. 21 CFR 582.60 - Synthetic flavoring substances and adjuvants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...). Geranyl acetate (geraniol acetate). Glycerol (glyceryl) tributyrate (tributyrin, butyrin). Limonene (d-, l... (benzoic aldehyde). N-Butyric acid (butanoic acid). d- or l-Carvone (carvol). Cinnamaldehyde...

  14. 21 CFR 582.60 - Synthetic flavoring substances and adjuvants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...). Geranyl acetate (geraniol acetate). Glycerol (glyceryl) tributyrate (tributyrin, butyrin). Limonene (d-, l... (benzoic aldehyde). N-Butyric acid (butanoic acid). d- or l-Carvone (carvol). Cinnamaldehyde...

  15. 21 CFR 582.60 - Synthetic flavoring substances and adjuvants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...). Geranyl acetate (geraniol acetate). Glycerol (glyceryl) tributyrate (tributyrin, butyrin). Limonene (d-, l... (benzoic aldehyde). N-Butyric acid (butanoic acid). d- or l-Carvone (carvol). Cinnamaldehyde...

  16. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) The acrylate ester copolymer is a fully polymerized copolymer of ethyl acrylate, methyl methacrylate... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl...

  17. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... polymerized copolymer of ethyl acrylate, methyl methacrylate, and methacrylic acid applied in emulsion form to... Glyceryl monostearate Methyl cellulose Mineral oil Paraffin wax Potassium hydroxide Potassium...

  18. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) The acrylate ester copolymer is a fully polymerized copolymer of ethyl acrylate, methyl methacrylate... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl...

  19. Nitroglycerin induces DNA damage and vascular cell death in the setting of nitrate tolerance.

    PubMed

    Mikhed, Yuliya; Fahrer, Jörg; Oelze, Matthias; Kröller-Schön, Swenja; Steven, Sebastian; Welschof, Philipp; Zinßius, Elena; Stamm, Paul; Kashani, Fatemeh; Roohani, Siyer; Kress, Joana Melanie; Ullmann, Elisabeth; Tran, Lan P; Schulz, Eberhard; Epe, Bernd; Kaina, Bernd; Münzel, Thomas; Daiber, Andreas

    2016-07-01

    Nitroglycerin (GTN) and other organic nitrates are widely used vasodilators. Their side effects are development of nitrate tolerance and endothelial dysfunction. Given the potential of GTN to induce nitro-oxidative stress, we investigated the interaction between nitro-oxidative DNA damage and vascular dysfunction in experimental nitrate tolerance. Cultured endothelial hybridoma cells (EA.hy 926) and Wistar rats were treated with GTN (ex vivo: 10-1000 µM; in vivo: 10, 20 and 50 mg/kg/day for 3 days, s.c.). The level of DNA strand breaks, 8-oxoguanine and O (6)-methylguanine DNA adducts was determined by Comet assay, dot blot and immunohistochemistry. Vascular function was determined by isometric tension recording. DNA adducts and strand breaks were induced by GTN in cells in vitro in a concentration-dependent manner. GTN in vivo administration leads to endothelial dysfunction, nitrate tolerance, aortic and cardiac oxidative stress, formation of DNA adducts, stabilization of p53 and apoptotic death of vascular cells in a dose-dependent fashion. Mice lacking O (6)-methylguanine-DNA methyltransferase displayed more vascular O (6)-methylguanine adducts and oxidative stress under GTN therapy than wild-type mice. Although we were not able to prove a causal role of DNA damage in the etiology of nitrate tolerance, the finding of GTN-induced DNA damage such as the mutagenic and toxic adduct O (6)-methylguanine, and cell death supports the notion that GTN based therapy may provoke adverse side effects, including endothelial function. Further studies are warranted to clarify whether GTN pro-apoptotic effects are related to an impaired recovery of patients upon myocardial infarction. PMID:27357950

  20. 21 CFR 172.832 - Monoglyceride citrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  1. 21 CFR 172.832 - Monoglyceride citrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  2. 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...

  3. 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,...

  4. Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and bovine blood vessels.

    PubMed

    Neubauer, Regina; Wölkart, Gerald; Opelt, Marissa; Schwarzenegger, Christine; Hofinger, Marielies; Neubauer, Andrea; Kollau, Alexander; Schmidt, Kurt; Schrammel, Astrid; Mayer, Bernd

    2015-02-15

    The vascular bioactivation of the antianginal drug nitroglycerin (GTN), yielding 1,2-glycerol dinitrate and nitric oxide or a related activator of soluble guanylate cyclase, is catalyzed by aldehyde dehydrogenase-2 (ALDH2) in rodent and human blood vessels. The essential role of ALDH2 has been confirmed in many studies and is considered as general principle of GTN-induced vasodilation in mammals. However, this view is challenged by an early report showing that diphenyleneiodonium, which we recently characterized as potent ALDH2 inhibitor, has no effect on GTN-induced relaxation of bovine coronary arteries (De La Lande et al., 1996). We investigated this issue and found that inhibition of ALDH2 attenuates GTN-induced coronary vasodilation in isolated perfused rat hearts but has no effect on relaxation to GTN of bovine and porcine coronary arteries. This observation is explained by low levels of ALDH2 protein expression in bovine coronary arteries and several types of porcine blood vessels. ALDH2 mRNA expression and the rates of GTN denitration were similarly low, excluding a significant contribution of ALDH2 to the bioactivation of GTN in these vessels. Attempts to identify the responsible pathway with enzyme inhibitors did not provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or GSH-S-transferase. Thus, the present manuscript describes a hitherto unrecognized pathway of GTN bioactivation in bovine and porcine blood vessels. If present in the human vasculature, this pathway might contribute to the therapeutic effects of organic nitrates that are not metabolized by ALDH2. PMID:25576686

  5. Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and bovine blood vessels

    PubMed Central

    Neubauer, Regina; Wölkart, Gerald; Opelt, Marissa; Schwarzenegger, Christine; Hofinger, Marielies; Neubauer, Andrea; Kollau, Alexander; Schmidt, Kurt; Schrammel, Astrid; Mayer, Bernd

    2015-01-01

    The vascular bioactivation of the antianginal drug nitroglycerin (GTN), yielding 1,2-glycerol dinitrate and nitric oxide or a related activator of soluble guanylate cyclase, is catalyzed by aldehyde dehydrogenase-2 (ALDH2) in rodent and human blood vessels. The essential role of ALDH2 has been confirmed in many studies and is considered as general principle of GTN-induced vasodilation in mammals. However, this view is challenged by an early report showing that diphenyleneiodonium, which we recently characterized as potent ALDH2 inhibitor, has no effect on GTN-induced relaxation of bovine coronary arteries (De La Lande et al., 1996). We investigated this issue and found that inhibition of ALDH2 attenuates GTN-induced coronary vasodilation in isolated perfused rat hearts but has no effect on relaxation to GTN of bovine and porcine coronary arteries. This observation is explained by low levels of ALDH2 protein expression in bovine coronary arteries and several types of porcine blood vessels. ALDH2 mRNA expression and the rates of GTN denitration were similarly low, excluding a significant contribution of ALDH2 to the bioactivation of GTN in these vessels. Attempts to identify the responsible pathway with enzyme inhibitors did not provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or GSH-S-transferase. Thus, the present manuscript describes a hitherto unrecognized pathway of GTN bioactivation in bovine and porcine blood vessels. If present in the human vasculature, this pathway might contribute to the therapeutic effects of organic nitrates that are not metabolized by ALDH2. PMID:25576686

  6. Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway.

    PubMed

    Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C; Tanaka, Leonardo Y; Fukai, Tohru; Laurindo, Francisco R M; Mason, Ronald P; Vasquez-Vivar, Jeannette; Minshall, Richard D; Stadler, Krisztian; Bonini, Marcelo G

    2012-01-15

    Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1-50nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP(3), probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID:22037515

  7. Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

    PubMed Central

    Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R.M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.

    2012-01-01

    Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1–50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID:22037515

  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. In vivo depletion of free thiols does not account for nitroglycerin-induced tolerance: a thiol-nitrate interaction hypothesis as an alternative explanation for nitroglycerin activity and tolerance.

    PubMed

    Haj-Yehia, A I; Benet, L Z

    1996-09-01

    The present study investigates the effects of thiol-depleting/ modifying agents on the activity of and tolerance to nitroglycerin (GTN), sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) in an in vivo rat model. Rats were treated with either vehicle (control), GTN (before and after induction of tolerance), diethyl maleate (a thiol-depleting agent) or N-ethylmaleimide (a thiol-modifying agent). The effects of GTN, SNP and SNAP on vascular cyclic GMP levels were investigated before and after each treatment. In addition, plasma and tissue thiol concentrations were measured in the same tissues as used for the determination of cyclic GMP in aorta and inferior vena cava after single and serial i.v. bolus doses of each drug. Depletion of free thiols (glutathione and cysteine) was not found to accompany tolerance development in GTN-treated tolerant rats or to significantly enhance tolerance development or augment its magnitude in diethyl maleate-treated rats. When rats were pretreated with a low single dose of N-ethylmaleimide, where no significant changes in vascular free thiols were observed, significant reduction in GTN- and SNP-induced, but not SNAP-induced, vascular cyclic GMP production was obtained. Considering the differential effects of diethyl maleate (mainly free thiol depletion) and N-ethylmaleimide (mainly proteinous thiol-alkylation) on vascular thiols, these results indicate that depletion of sulfhydryl groups other than those from free glutathione and cysteine seems to be involved in the mechanisms defining GTN and SNP (but not SNAP) action and tolerance. Here we propose that SNAP may act either directly by nitrosation of the heme moiety of the enzyme or via an S-enzyme-S-drug transnitrosation reaction, whereas GTN and SNP actions are mediated by the formation of S-nitrosothiol on the enzyme itself, rather than by activation of the enzyme by free S-nitrosothiols. PMID:8819515

  10. 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

  11. Fatal Cases of Gestational Trophoblastic Neoplasia in a National Trophoblastic Disease Reference Center in Dakar Senegal

    PubMed Central

    Gueye, Mamour; Ndiaye-Gueye, Mame Diarra; Kane Gueye, Serigne Modou; Moreau, Jean Charles

    2016-01-01

    Objectives: The objectives of this study were to analyze deaths after gestational trophoblastic neoplasia and to determine the factors of treatment failure. Methods: This is a retrospective study in Aristide Le Dantec teaching Hospital in Dakar, Senegal, between 1 January 2006 and 31 December 2014. We took into account socio-epidemiological characteristics of patients, initial diagnosis, time between uterine evacuation and admission, time to onset of gestational trophoblastic neoplasia (GTN), treatment received (deadlines, protocols), difficulties experienced in the diagnosis and the initiation of treatment and survival. Results: In total, 1044 patients were admitted during the study period; 164 cases of GTN were diagnosed (15.7%); and 21 deaths occurred leading to a specific lethality of 12.8%. The average age was 30 years. Almost all patients (n = 18; 85.7%) had low income or no income. Eight out of 21 patients (38.1%) were seen in our department after GTN onset. The mean time to onset of GTN of all patients was 22.1 weeks. For 66.6%, histology was not available; the diagnosis of hydatidiform mole was made on the clinical history and sonographic features and GTN on human chorionic gonadotrophin (hCG) evolution and ultrasound findings. None of the patients had regular chemotherapy due to financial reasons. Patients who died within 3 months after diagnosis had metastatic tumors (7 of 21). All these women had resistance to treatment or progressed after three courses of chemotherapy. Ten of the 12 women with high-risk GTN were not treated with multi-agent chemotherapy (EMA-CO) for purely financial reasons. Conclusion and Global Health Implications: The high incidence and mortality require a profound reorganization of our health system and a high awareness of practitioners to refer to time or to declare all suspected cases of hydatidiform mole or gestational trophoblastic neoplasia. PMID:27622010

  12. 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. PMID:26566708

  13. 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.

  14. 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%). PMID:26562155

  15. 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...

  16. 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

  17. Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African Americans

    PubMed Central

    Seu, Lillian; Burt, Trevor D.; Witte, John S.; Martin, Jeffrey N.; Deeks, Steven G.; McCune, Joseph M.

    2012-01-01

    Heme oxygenase-1 (HO-1) is an anti-inflammatory enzyme that maintains homeostasis during cellular stress. Given previous findings that shorter length variants of a HO-1 promoter-region GTn microsatellite polymorphism are associated with increased HO-1 expression in cell lines, we hypothesized that shorter variants would also be associated with increased levels of HO-1 expression, less inflammation, and lower levels of inflammation-associated viral replication in HIV-infected subjects. Healthy donors (n=20) with shorter GTn repeats had higher HO-1 mRNA transcript in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS) (r= −0.38, p=0.05). The presence of fewer GTn repeats in subjects with untreated HIV disease was associated with higher HO-1 mRNA levels in peripheral blood (r= −0.41, p=0.02); similar observations were made in CD14+ monocytes from antiretroviral-treated subjects (r= −0.36, p=0.04). In African-Americans, but not Caucasians, greater GTn repeats were correlated with higher soluble CD14 (sCD14) levels during highly active antiretroviral therapy (HAART) (r= 0.38, p=0.007) as well as higher mean viral load off-therapy (r= 0.24, p=0.04). These data demonstrate that the HO-1 GTn microsatellite polymorphism is associated with higher levels of HO-1 expression and that this pathway may have important effects on the association between inflammation and HIV replication. PMID:22048453

  18. 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

  19. In vitro drug release mechanism and drug loading studies of cubic phase gels.

    PubMed

    Lara, Marilisa G; Bentley, M Vitória L B; Collett, John H

    2005-04-11

    Glyceryl monooleate/water cubic phase systems were investigated as drug delivery systems, using salicylic acid as a model drug. The liquid crystalline phases formed by the glyceryl monooleate (GMO)/water systems were characterized by polarizing microscopy. In vitro drug release studies were performed and the influences of initial water content, swelling and drug loading on the drug release properties were evaluated. Water uptake followed second-order swelling kinetics. In vitro release profiles showed Fickian diffusion control and were independent on the initial water content and drug loading, suggesting GMO cubic phase gels suitability for use as drug delivery system. PMID:15778062

  20. Incorporation of phosphatidylglycerol into murein lipoprotein in intact cells of Salmonella typhimurium by phospholipid vesicle fusion.

    PubMed Central

    Chattopadhyay, P K; Lai, J S; Wu, H C

    1979-01-01

    The biosynthesis of the diglyceride moiety of murein lipoprotein was studied by fusion of labeled phospholipid vesicles with intact cells of Salmonella typhimurium. Phosphatidylglycerol was found to be an excellent donor for the glyceryl moiety in lipoprotein, whereas phosphatidylethanolamine and cardiolipin were not. The incorporation of radioactivity from monoacyl-phosphatidylglycerol into lipoprotein can be attributed to its conversion to phosphatidylglycerol. The results strongly support our hypothesis that the glyceryl residue covalently linked to murein lipoprotein is derived from the nonacylated glycerol moiety of phosphatidylglycerol. PMID:368018

  1. 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...

  2. 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...

  3. 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...

  4. 75 FR 20785 - Polyglyceryl Phthalate Ester of Coconut Oil Fatty Acids; Exemption from the Requirement of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... . II. What Does this Correction Do? In the Federal Register of July 8, 2009, (74 FR 32456), EPA's... of polyglyceryl phthalate ester of coconut oil fatty acids, including fatty acid coco polymers with... acid coco of surfactants polymers with glyceryl and phthalic anhydride (CAS No. 67746-02-5) and...

  5. Antihistamine Effect of a Pure Bioactive Compound Isolated from Slug (Diplosolenodes occidentalis) Material

    PubMed Central

    Jacob, AS; Simon, OR; Wheatle, D; Ruddock, P; McCook, K

    2014-01-01

    ABSTRACT Objective: Folklore claims of the therapeutic effect of garden slug (Diplosolenodes occidentalis) extract used to relieve bronchoconstriction in asthmatic individuals were never validated scientifically. The aim of this study was to isolate the pure bioactive compound from slug extract causing this effect. Methods: The crude ground material was prepared in ethanol and after filtration, separation by flash column chromatography method was done. The structure was elucidated by data from hydrogen and carbon nuclear magnetic resonance (NMR) profiles. The bioactive compound was assessed for dose dependent response effects on guinea pig tracheal smooth muscle pre-contracted with histamine. Receptor specificity studies were done by using HTMT dimaleate (H1 agonist). The type of antagonism was also identified. Results: The pure component isolated from garden slug material was identified by spectral studies as glyceryl trilinolenate. It caused dose-dependent relaxation in guinea pig tracheal smooth muscle strips pre-contracted with histamine, it acted via H1 type receptors and showed non-competitive antagonism. Conclusion: Glyceryl trilinolenate produced dose-dependent relaxation in tracheal smooth muscle strips in the presence of the agonist histamine. Glyceryl trilinolenate displayed non-competitive antagonism at H1 receptors in the trachea. This agent was able to alleviate bronchoconstriction in individuals presenting with atopic asthma in rural agricultural areas in Jamaica (verbal communications). It is possible that glyceryl trilinolenate can be used therapeutically to produce tracheal smooth muscle relaxation in individuals presenting with atopic asthma. PMID:25781274

  6. 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. PMID:26656946

  7. 76 FR 21339 - Certain New Chemicals; Receipt and Status Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ...)-, reaction products with bu glycidyl ether* P-11-0043......... 10/26/10 01/23/11 Gelest, Inc. (S) Conversion... alkanediol and cyclic ether, alkanoate P-11-0054......... 11/03/10 01/31/11 Mane, USA (G) Perfumery (S) 2H...) A component (G) Glyceryl in ultraviolet polypropylene light/electron glycol ether beam...

  8. The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products.

    PubMed

    Woodward, D F; Carling, R W C; Cornell, C L; Fliri, H G; Martos, J L; Pettit, S N; Liang, Y; Wang, J W

    2008-10-01

    The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation. PMID:18700152

  9. The Global Terrestrial Network for Glaciers: an overview of recent activities

    NASA Astrophysics Data System (ADS)

    Arendt, Anthony

    2015-04-01

    The Global Terrestrial Network for Glaciers (GTN-G) is an organizational framework for three operational bodies dedicated to global mapping and monitoring of glacier changes. In this talk I will provide an overview of recent progress made by the World Glacier Monitoring Service (WGMS), the National Snow and Ice Data Center (NSIDC) and the Global Land Ice Measurements from Space (GLIMS) toward distribution and analysis of global in-situ and remotely sensed glacier observations. I will highlight new initiatives aimed at database integration, modernization of internet-based tools, and enhanced community outreach. These activities are helping to generate new discoveries in cryospheric studies, which I will illustrate through several example applications. Finally, I will outline a vision for future GTN-G efforts that will enable rapid response to anticipated glacier variations resulting from climate variability.

  10. International glacier monitoring and data archiving, from a national perspective

    NASA Astrophysics Data System (ADS)

    Andreassen, Liss M.

    2016-04-01

    The Global Terrestrial Network for Glaciers (GTN-G) is a framework for internationally coordinated monitoring of glaciers and ice caps and run by three operational bodies: 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 talk, I will present recent progresses by GTN-G in efforts to store and provide extensive glaciological data to the community. I will also discuss some of the challenges in monitoring and data archiving, illustrated with examples from my own experiences as a data provider. Finally, I would like to discuss how we as a community could enrich and complete existing databases.

  11. 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

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

    PubMed

    Aminimoghaddam, Soheila; Karisani, Narmin; 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

  13. Dual-stimuli-responsive drug release from interpenetrating polymer network-structured hydrogels of gelatin and dextran.

    PubMed

    Kurisawa, M; Yui, N

    1998-07-31

    Interpenetrating polymer network (IPN)-structured hydrogels of gelatin (Gtn) and dextran (Dex) were prepared with lipid microspheres (LMs) as a drug microreservoir, and LM release from these hydrogels was examined in relation to their dual-stimuli-responsive degradation. A phase morphology in the IPN-structured hydrogels was varied with the preparation temperature, i.e. above or below the sol-gel transition temperature (Ttrans) of Gtn. The IPN-structured hydrogel prepared below Ttrans exhibited a specific degradation-controlled LM release behavior: LM release from the hydrogel in the presence of either alpha-chymotrypsin or dextranase alone was completely hindered, whereas LM release was observed in the presence of both enzymes. It is concluded that dual-stimuli-responsive drug release can be achieved by specific degradation of a particular IPN-structured hydrogel. PMID:9724906

  14. Single synchronous pulmonary metastasis from placental site trophoblastic tumor and teratoma.

    PubMed

    Billè, Andrea; Girelli, Lara; Colecchia, Maurizio; Pastorino, Ugo

    2015-01-01

    Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic tumor (GTN), accounting for 1-2% of all GTNs. Primary testicular PSTTs are extremely rare. Thirty percent of patients with PSTT show multiple lung and brain metastases at the time of diagnosis. We present the first case of a synchronous single pulmonary trophoblastic placental tumor metastasis together with a teratoma and a mixed germinal tumor of the testis, treated with minimally invasive lung metastasectomy. PMID:25908040

  15. Acute changes in forearm venous volume and tone using radionuclide plethysmography

    SciTech Connect

    Manyari, D.E.; Malkinson, T.J.; Robinson, V.; Smith, E.R.; Cooper, K.E.

    1988-10-01

    In this investigation blood pool scintigraphy was validated as a method to study acute changes in human forearm veins. Changes in regional forearm vascular volume (capacity) and the occluding pressure-volume (P-V) relationship induced by sublingual nifedipine (NIF) and nitroglycerin (GTN) were recorded in 16 patients with simultaneous data collection by the radionuclide and the mercury-in-rubber strain-gauge techniques. The standard error of estimate (Syx) between successive control measurements using the radionuclide method was 3.1% compared with 3.2% for the strain-gauge method. The venous P-V curves were highly reproducible using both techniques. Strain gauge and radionuclide measurements of acute changes in forearm venous volume correlated well (r = 0.86; Syx = 7%, n = 156). After 20 mg of NIF or 0.6 mg of GTN, mean heart rate increased from 71 +/- 10 to 77 +/- 9 and from 68 +/- 10 to 75 +/- 11 beats/min, respectively, and group systolic blood pressure decreased from 128 +/- 22 to 120 +/- 19 and from 136 +/- 18 to 126 +/- 23 mmHg, respectively (P less than 0.05). At venous occluding pressures of 0 and 30 mmHg, the forearm vascular volume did not change after NIF (2 +/- 4 and -1 +/- 4%; P greater than 0.05), whereas it increased after GTN (8 +/- 5 and 12 +/- 7%; P less than 0.001). The forearm venous P-V relationship did not change after NIF, whereas a significant rightward shift (venodilation, with an increase in unstressed volume) occurred after GTN.

  16. Estimating Riverine Water and Constiuent Fluxes in a Data Assimilation Framework

    NASA Astrophysics Data System (ADS)

    Fekete, B. M.; Saile, P.

    2012-12-01

    River systems are the primary means of transporting waters over the landscape from headwaters to basin mouth while carrying various constituents. Rivers give home to diverse aquatic habitats, while serving humans water needs. River discharge is the most accurately measured component of the hydrological cycle, when it is carried out on the ground using traditional in-situ measurements. While in-situ river monitoring is cost competitive to remote sensing alternatives, comprehensive water flux assessments need to combine in-situ and remote sensing observations with hydrological modeling. The capabilities of in-situ vs. remote sensing sensors are largely complementary that data assimilation frameworks built on top of hydrological models can utilize. The Global Terrestrial Networks for Hydrology (GTN-H) effort of the World Meteorological Organization (WMO) was designed to implement such data assimilation on top of the data assets from its partner institutions. GTN-H seeks to hold a comprehensive repository of a wide range of hydrological information ranging from climate data (including various reanalysis and precipitation data products) that are available for near realtime hydrological simulations, in-situ discharge records collected by the Global Runoff Data Centre, Koblenz, Germany, complemented by key water quality variables from UNEP's Global Environmental Monitoring - Water (GEMS/Water) programme. The modeling platform serving GTN-H is currently built on the Framework for Aquatic Modeling of the Earth System (FrAMES) developed by the CUNY Environmental CrossRoads Initiative with contributions from the University of New Hampshire and Colorado University. FrAMES offers high degree of flexibility in configuring large scale hydrological simulations coupled with the capability of tracking dissolved and suspended constituents. This presentation will show the key components of the GTN-H data archive and the application of FrAMES to produce value added hydrological

  17. Anti-inflammatory therapies in TRAMP mice: delay in PCa progression.

    PubMed

    Kido, Larissa Akemi; Montico, Fabio; Sauce, Rafael; Macedo, Aline Barbosa; Minatel, Elaine; Costa, Débora Barbosa Vendramini; de Carvalho, João Ernesto; Pilli, Ronaldo Aloise; Cagnon, Valeria Helena Alves

    2016-04-01

    The aim of this study was to characterize the structural and molecular biology as well as evaluate the immediate and late responses of prostatic cancer in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model after treatment with goniothalamin (GTN) and celecoxib. The treated mice received GTN (150 mg/kg, gavage) or celecoxib (10 mg/kg, gavage) from 8 to 12 weeks of age. They were killed at different ages: the immediate-response groups at 12 weeks and the late-response groups at 22 weeks. The ventral prostate was collected for light microscopy, immunohistochemistry, western blotting, TUNEL, and ELISA. Morphological analyses indicated that GTN treatment delayed the progression of prostatic adenocarcinoma, leading to a significant decrease of prostatic lesion frequency in both experimental period responses to this treatment, mainly high-grade prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma. Also, the celecoxib treatment showed a particular decrease in the proliferative processes (PCNA) in both the experimental periods. Despite celecoxib diminishing the COX2 and IGFR1 levels, GTN presented higher action spectrum considering the decrease of a greater molecular number involved in the proliferative and inflammatory processes in prostatic cancer. Goniothalamin attenuated the pro-inflammatory response in TRAMP prostatic microenvironment, delaying prostate cancer (PCa) progression. Celecoxib treatment was efficient in the regulation of COX2 in the TRAMP mice, mainly in the advanced disease grade. Finally, we concluded that inflammatory process control in early grades of PCa was crucial for the downregulation of the signaling pathways involved in the proliferative processes in advanced cancer grades. PMID:26772819

  18. Likelihood and Bayesian analyses reveal major genes affecting body composition, carcass, meat quality and the number of false teats in a Chinese European pig line

    PubMed Central

    Marie-Pierre, Sanchez; Bidanel, Jean-Pierre; Zhang, Siqing; Naveau, Jean; Burlot, Thierry; Le Roy, Pascale

    2003-01-01

    Segregation analyses were performed using both maximum likelihood – via a Quasi Newton algorithm – (ML-QN) and Bayesian – via Gibbs sampling – (Bayesian-GS) approaches in the Chinese European Tiameslan pig line. Major genes were searched for average ultrasonic backfat thickness (ABT), carcass fat (X2 and X4) and lean (X5) depths, days from 20 to 100 kg (D20100), Napole technological yield (NTY), number of false (FTN) and good (GTN) teats, as well as total teat number (TTN). The discrete nature of FTN was additionally considered using a threshold model under ML methodology. The results obtained with both methods consistently suggested the presence of major genes affecting ABT, X2, NTY, GTN and FTN. Major genes were also suggested for X4 and X5 using ML-QN, but not the Bayesian-GS, approach. The major gene affecting FTN was confirmed using the threshold model. Genetic correlations as well as gene effect and genotype frequency estimates suggested the presence of four different major genes. The first gene would affect fatness traits (ABT, X2 and X4), the second one a leanness trait (X5), the third one NTY and the last one GTN and FTN. Genotype frequencies of breeding animals and their evolution over time were consistent with the selection performed in the Tiameslan line. PMID:12927073

  19. Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm.

    PubMed

    Peng, Mei; Ding, Yiling; Yu, Ling; Deng, Yali; Lai, Weisi; Hu, Yun; Zhang, Hongwen; Wu, Xianqing; Fan, Hong; Ding, Hui; Wu, Yilin; Tao, Guangshi

    2015-01-01

    Although 5-fluorouracil (5-Fu) combination chemotherapy provides a satisfactory therapeutic response in patients with gestational trophoblastic neoplasms (GTNs), it has severe side effects. The current study analyzed the therapeutic effects and side effects of tegafur plus actinomycin D (Act-D) vs. 5-Fu plus Act-D for the treatment of GTNs based on controlled historical records. A total of 427 GTN cases that received tegafur and Act-D combination chemotherapy at the Second Xiangya Hospital of XiangYa Medical School between August 2003 and July 2013 were analyzed based on historical data. A total of 393 GTN cases that received 5-Fu plus Act-D between August 1993 and July 2003 at the same hospital were also analyzed, which constituted the control group. The therapeutic effects, toxicity and side effects after chemotherapy were compared between the groups. The overall response rate was 90.63% in the tegafur+Act-D group (tegafur group) and 92.37% in the 5-Fu+Act-D group (5-Fu group); these rates were not significantly different (P > 0.05). However, the incidence rates of myelosuppression (white blood cell decline), gastrointestinal reactions (nausea, vomiting, dental ulcer, and diarrhea), skin lesions and phlebitis were lower in the tegafur group than in the 5-Fu group (P < 0.05). The results of this study may provide useful data for the clinical application of tegafur in GTN treatment. PMID:26599757

  20. Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm

    PubMed Central

    Peng, Mei; Ding, Yiling; Yu, Ling; Deng, Yali; Lai, Weisi; Hu, Yun; Zhang, Hongwen; Wu, Xianqing; Fan, Hong; Ding, Hui; Wu, Yilin; Tao, Guangshi

    2015-01-01

    Although 5-fluorouracil (5-Fu) combination chemotherapy provides a satisfactory therapeutic response in patients with gestational trophoblastic neoplasms (GTNs), it has severe side effects. The current study analyzed the therapeutic effects and side effects of tegafur plus actinomycin D (Act-D) vs. 5-Fu plus Act-D for the treatment of GTNs based on controlled historical records. A total of 427 GTN cases that received tegafur and Act-D combination chemotherapy at the Second Xiangya Hospital of XiangYa Medical School between August 2003 and July 2013 were analyzed based on historical data. A total of 393 GTN cases that received 5-Fu plus Act-D between August 1993 and July 2003 at the same hospital were also analyzed, which constituted the control group. The therapeutic effects, toxicity and side effects after chemotherapy were compared between the groups. The overall response rate was 90.63% in the tegafur+Act-D group (tegafur group) and 92.37% in the 5-Fu+Act-D group (5-Fu group); these rates were not significantly different (P > 0.05). However, the incidence rates of myelosuppression (white blood cell decline), gastrointestinal reactions (nausea, vomiting, dental ulcer, and diarrhea), skin lesions and phlebitis were lower in the tegafur group than in the 5-Fu group (P < 0.05). The results of this study may provide useful data for the clinical application of tegafur in GTN treatment. PMID:26599757

  1. 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

  2. Reduction of aliphatic nitroesters and N-nitramines by Enterobacter cloacae PB2 pentaerythritol tetranitrate reductase: quantitative structure-activity relationships.

    PubMed

    Nivinskas, Henrikas; Sarlauskas, Jonas; Anusevicius, Zilvinas; Toogood, Helen S; Scrutton, Nigel S; Cenas, Narimantas

    2008-12-01

    Enterobacter cloacae PB2 NADPH:pentaerythritol tetranitrate reductase (PETNR) performs the biodegradation of explosive organic nitrate esters via their reductive denitration. In order to understand the enzyme substrate specificity, we have examined the reactions of PETNR with organic nitrates (n = 15) and their nitrogen analogues, N-nitramines (n = 4). The reactions of these compounds with PETNR were accompanied by the release of 1-2 mol of nitrite per mole of compound, but were not accompanied by their redox cycling and superoxide formation. The reduction rate constants (k(cat)/K(m)) of inositol hexanitrate, diglycerol tetranitrate, erythritol tetranitrate, mannitol hexanitrate and xylitol pentanitrate were similar to those of the established PETNR substrates, PETN and glycerol trinitrate, whereas the reactivities of hexahydro-1,3,5-trinitro-1,3,5-triazine and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine were three orders of magnitude lower. The log k(cat)/K(m) value of the compounds increased with a decrease in the enthalpy of formation of the hydride adducts [DeltaH(f)(R-O-N(OH)O(-)) or DeltaH(f)(R(1),R(2) > N-N(OH)O(-))], and with an increase in their lipophilicity (octanol/water partition coefficient, log P(ow)), and did not depend on their van der Waals' volumes. Hydrophobic organic nitroesters and hydrophilic N-nitramines compete for the same binding site in the reduced enzyme form. The role of the hydrophobic interaction of PETNR with glycerol trinitrate was supported by the positive dependence of glycerol trinitrate reactivity on the solution ionic strength. The discrimination of nitroesters and N-nitramines according to their log P(ow) values seems to be a specific feature of the Old Yellow Enzyme family of flavoenzymes. PMID:19016851

  3. Biodegradation of Glycidol and Glycidyl Nitrate †

    PubMed Central

    Kaplan, David L.; Cornell, John H.; Kaplan, Arthur M.

    1982-01-01

    When calcium hydroxide is used to desensitize glycerol trinitrate (nitroglycerine)-containing waste streams, the epoxides glycidol and glycidyl nitrate are formed. The epoxide rings of both compounds are unstable to heat in aqueous solutions, and they open to form glycerol 1-mononitrate and presumably glycerol. These transformations were accelerated by microbial activity. Glycerol 1-mononitrate was slowly denitrated to form glycerol. Glycidol and glycidyl nitrate caused base-pair substitutions in the Ames test for mutagenicity, whereas glycerol 1-mononitrate tests were negative. PMID:16345917

  4. 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

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

    PubMed

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

    1989-04-01

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

  6. 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.

  7. 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...

  8. 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

  9. 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

  10. Comparative studies of lamivudine-zidovudine nanoparticles for the selective uptake by macrophages.

    PubMed

    Sankar, V; Nareshkumar, Parmar Nilaykumar; Ajitkumar, Gohel Nishit; Penmetsa, Shalini Devi; Hariharan, Sivaram

    2012-09-01

    The present study investigates the specific drug targeting of anti retroviral drugs, such as lamivudine and zidovudine, after intraperitoneal (i.p) injection by incorporation into polymeric nanoparticles (PNs) and solid lipid nanoparticles (SLNs). Our results showed that Glyceryl Monosterate-Poloxamer 188 SLNs (average diameter of 522.466 nm) showed slow drug release rates (63.18% of lamivudine and 62.37% of zidovudine were released in 12 hrs) among all the SLN formulations. For Poly lactic-co-glycolic acid (PLGA)-Poloxamer 188 PNs (average diameter of 70.348 nm), there were faster release rates of both lamivudine and zidovudine (97% and 94.06%, respectively, in 12 hrs). Tissue distribution studies were carried out in mice and concentrations of drugs in different organs were determined using high performance liquid chromatography (HPLC) after i.p. administration. Glyceryl Monosterate-Poloxamer 188 SLNs and PLGA-Poloxamer 188 PNs showed increase in the distribution of lamivudine and zidovudine to liver and spleen when compared to the drugs in solution. Also, Glyceryl Monosterate-P 188 SLNs showed higher concentration of drugs in RES organs than PLGA-P 188 PNs. PMID:22452408

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

    PubMed Central

    Wang, L L; Johnson, E A

    1992-01-01

    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. Images PMID:1610184

  12. 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. PMID:21770719

  13. Effects of dietary carbohydrate on hepatic de novo lipogenesis in European seabass (Dicentrarchus labrax L.).

    PubMed

    Viegas, Ivan; Jarak, Ivana; Rito, João; Carvalho, Rui A; Metón, Isidoro; Pardal, Miguel A; Baanante, Isabel V; Jones, John G

    2016-07-01

    Farmed seabass have higher adiposity than their wild counterparts and this is often attributed to carbohydrate (CHO) feeding. Whether this reflects a reduction in fat oxidation, increased de novo lipogenesis (DNL), or both, is not known. To study the effects of high CHO diets on hepatic TG biosynthesis, hepatic TG deuterium ((2)H) enrichment was determined following 6 days in (2)H-enriched tank water for fish fed with a no-CHO control diet (CTRL), and diets with digestible starch (DS) and raw starch (RS). Hepatic fractional synthetic rates (FSRs, percent per day(-1)) were calculated for hepatic TG-glyceryl and FA moieties through (2)H NMR analysis. Glyceryl FSRs exceeded FA FSRs in all cases, indicating active cycling. DS fish did not show increased lipogenic potential compared to CTRL. RS fish had lower glyceryl FSRs compared with the other diets and negligible levels of FA FSRs despite similar hepatic TG levels to CTRL. DS-fed fish showed higher activity for enzymes that can provide NADPH for lipogenesis, relative to CTRL in the case of glucose-6-phosphate dehydrogenase (G6PDH) and relative to RS for both G6PDH and 6-phosphogluconate dehydrogenase. This approach indicated that elevated hepatic adiposity from DS feeding was not attributable to increased DNL. PMID:27247346

  14. 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.

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

    PubMed

    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

  16. Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure.

    PubMed

    Daiber, Andreas; Oelze, Matthias; Coldewey, Meike; Kaiser, K; Huth, C; Schildknecht, S; Bachschmid, M; Nazirisadeh, Y; Ullrich, V; Mülsch, A; Münzel, T; Tsilimingas, N

    2005-12-30

    The hemodynamic and anti-ischemic effects of nitroglycerin (GTN) are rapidly blunted as a result of the development of nitrate tolerance. Hydralazine has been shown to prevent tolerance in experimental and clinical studies, all of which may be at least in part secondary to antioxidant properties of this compound. The antioxidant effects of hydralazine were tested in cell free systems, cultured smooth muscle cells, isolated mitochondria, and isolated vessels. Inhibitory effects on the formation of superoxide and/or peroxynitrite formation were tested using lucigenin and L-012 enhanced chemiluminescence as well as DHE-fluorescence. The peroxynitrite scavenging properties were also assessed by inhibition of nitration of phenol. Prevention of impairment of NO downstream signaling and GTN bioactivation was determined by measurement of P-VASP (surrogate parameter for the activity of the cGMP-dependent kinase-I, cGK-I) and mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Hydralazine dose-dependently decreased the chemiluminescence signal induced by peroxynitrite from SIN-1 and by superoxide from HX/XO in a cell free system, by superoxide in smooth muscle cells and mitochondria acutely challenged with GTN. Moreover, hydralazine inhibited the peroxynitrite-mediated nitration of phenols as well as proteins in smooth muscle cells in a dose-dependent fashion. Finally, hydralazine normalized impaired cGK-I activity as well as impaired vascular ALDH-2 activity. Our results indicate that hydralazine is a highly potent radical scavenger. Thus, the combination with isosorbide dinitrate (ISDN) will favorably influence the nitroso-redox balance in the cardiovascular system in patients with congestive heart failure and may explain at least in part the improvement of prognosis in patients with chronic congestive heart failure. PMID:16289107

  17. 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.

  18. 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.

  19. Alternative 5’ Untranslated Regions Are Involved in Expression Regulation of Human Heme Oxygenase-1

    PubMed Central

    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. PMID:24098580

  20. 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.

  1. 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.

  2. Injectable 3D hydrogel scaffold with tailorable porosity post-implantation.

    PubMed

    Al-Abboodi, Aswan; Fu, Jing; Doran, Pauline M; Tan, Timothy T Y; Chan, Peggy P Y

    2014-05-01

    Since rates of tissue growth vary significantly between tissue types, and also between individuals due to differences in age, dietary intake, and lifestyle-related factors, engineering a scaffold system that is appropriate for personalized tissue engineering remains a significant challenge. In this study, a gelatin-hydroxyphenylpropionic acid/carboxylmethylcellulose-tyramine (Gtn-HPA/CMC-Tyr) porous hydrogel system that allows the pore structure of scaffolds to be altered in vivo after implantation is developed. Cross-linking of Gtn-HPA/CMC-Tyr hydrogels via horseradish peroxidase oxidative coupling is examined both in vitro and in vivo. Post-implantation, further alteration of the hydrogel structure is achieved by injecting cellulase enzyme to digest the CMC component of the scaffold; this treatment yields a structure with larger pores and higher porosity than hydrogels without cellulase injection. Using this approach, the pore sizes of scaffolds are altered in vivo from 32-87 μm to 74-181 μm in a user-controled manner. The hydrogel is biocompatible to COS-7 cells and has mechanical properties similar to those of soft tissues. The new hydrogel system developed in this work provides clinicians with the ability to tailor the structure of scaffolds post-implantation depending on the growth rate of a tissue or an individual's recovery rate, and could thus be ideal for personalized tissue engineering. PMID:24151286

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

    PubMed

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

    2015-04-01

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

  4. The fusion of erythrocytes by fatty acids, esters, retinol and alpha-tocopherol.

    PubMed

    Ahkong, Q F; Fisher, D; Tampion, W; Lucy, J A

    1973-09-01

    1. The ability of a number of carboxylic acids, their esters, retinol and alpha-tocopherol to induce fusion of hen erythrocytes in vitro was investigated. 2. Some 30 different fat-soluble substances (100mug/ml) were found to cause the formation of multinucleated erythrocytes with a suspension of 3x10(8) erythrocytes/ml. The most effective agents induced fusion within 5-10min at 37 degrees C; some substances required about 1h. 3. Inclusion of Dextran 60C in the test medium minimized colloid osmotic lysis caused by exogenous lipids that induce cell fusion. 4. Cell swelling, followed by cell adhesion, was then seen to precede cell fusion. 5. Fusion occurred with C(10)-C(14) saturated carboxylic acids, with unsaturated, longer-chain carboxylic acids and their mono-esters; retinol, and to a lesser extent alpha-tocopherol, also caused cell fusion. 6. C(6)-C(9), C(15), C(16) and C(18) saturated carboxylic acids did not induce fusion within 4h; glyceryl dioleate was only weakly active, and glyceryl trioleate was inactive in the test system. 7. Fusion was facilitated by a high ratio of chemical agents to cell number and by incubation between pH5 and 6. It was inhibited by EDTA and by serum albumin. 8. Glyceryl mono-oleate caused both a similar fusion of several species of mammalian erythrocyte and the interspecific fusion of human and chicken erythrocytes. 9. The term ;fusogenic' is proposed to describe chemical, viral and physical agents that cause membranes to fuse. 10. The biochemical mechanisms involved and the possible biological significance of membrane fusion by fusogenic lipids are discussed. PMID:4204034

  5. Anti-glioma activity and the mechanism of cellular uptake of asiatic acid-loaded solid lipid nanoparticles.

    PubMed

    Garanti, Tanem; Stasik, Aneta; Burrow, Andrea Julie; Alhnan, Mohamed A; Wan, Ka-Wai

    2016-03-16

    Asiatic acid (AA), a pentacyclic triterpene found in Centella Asiatica, has shown neuroprotective and anti-cancer activity against glioma. However, owing to its poor aqueous solubility, effective delivery and absorption across biological barriers, in particular the blood brain barrier (BBB), are challenging. Solid lipid nanoparticles (SLNs) have shown a promising potential as a drug delivery system to carry lipophilic drugs across the BBB, a major obstacle in brain cancer therapy. Nevertheless, limited information is available about the cytotoxic mechanisms of nano-lipidic carriers with AA on normal and glioma cells. This study assessed the anti-cancer efficacy of AA-loaded SLNs against glioblastoma and their cellular uptake mechanism in comparison with SVG P12 (human foetal glial) cells. SLNs were systematically investigated for three different solid lipids; glyceryl monostearate (MS), glyceryl distearate (DS) and glyceryl tristearate (TS). The non-drug containing MS-SLNs (E-MS-SLNs) did not show any apparent toxicity towards normal SVG P12 cells, whilst the AA-loaded MS-SLNs (AA-MS-SLNs) displayed a more favourable drug release profile and higher cytotoxicity towards U87 MG cells. Therefore, MS-SLNs were chosen for further in vitro studies. Cytotoxicity studies of SLNs (± AA) were performed using MTT assay where AA-SLNs showed significantly higher cytotoxicity towards U87 MG cells than SVG P12 normal cells, as confirmed by flow cell cytometry. Cellular uptake of SLNs also appeared to be preferentially facilitated by energy-dependent endocytosis as evidenced by fluorescence imaging and flow cell cytometry. Using the Annexin V-PI double staining technique, it was found that these AA-MS-SLNs displayed concentration-dependent apoptotic activity on glioma cells, which further confirms the potential of exploiting these AA-loaded MS-SLNs for brain cancer therapy. PMID:26775062

  6. Short-Chain Flavor Ester Synthesis in Organic Media by an E. coli Whole-Cell Biocatalyst Expressing a Newly Characterized Heterologous Lipase

    PubMed Central

    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. PMID:24670408

  7. 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.

  8. Lipid nanoparticles for oral delivery of raloxifene: optimization, stability, in vivo evaluation and uptake mechanism.

    PubMed

    Ravi, Punna Rao; Aditya, N; Kathuria, Himanshu; Malekar, Srinivas; Vats, Rahul

    2014-05-01

    Raloxifene HCl (RLX) shows low oral bioavailability (<2%) in humans due to poor aqueous solubility and extensive (>90%) metabolism in gut. Lipid nanoparticles (SLN) with glyceryl tribehenate were designed to enhance drug's oral bioavailability. Box-Bhenken design was used to optimize manufacturing conditions. Optimized SLN had particle size of 167±3nm and high encapsulation efficiency (>92%). Oral bioavailability of RLX from SLN was improved by 3.24 folds compared to free RLX in female Wistar rats. Both clathrin and caveolae mediated endocytosis pathways were involved in the uptake of SLN. Lymphatic transport inhibitor, cycloheximide significantly reduced oral bioavailability of SLN. PMID:24378615

  9. Concise synthesis of ether analogues of lysobisphosphatidic acid.

    PubMed

    Jiang, Guowei; Xu, Yong; Falguières, Thomas; Gruenberg, Jean; Prestwich, Glenn D

    2005-09-01

    We describe a versatile, efficient method for the preparation of ether analogues of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer from (S)-solketal. Phosphorylation of a protected sn-2-O-octadecenyl glyceryl ether with 2-cyanoethyl bis-N,N-diisopropylamino phosphine and subsequent deprotection generated the bisether LBPA analogues. By simply changing the sequence of deprotection steps, we obtained the (R,R)- and (S,S)-enantiomers of 2,2'-bisether LBPA. An ELISA assay with anti-LBPA monoclonal antibodies showed that the bisether LBPAs were recognized with the same affinity as the natural 2,2'-bisoleolyl LBPA. [reaction: see text] PMID:16119911

  10. 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.

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

    PubMed

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

    2016-01-01

    Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR. PMID:24866725

  12. 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. PMID:2373957

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

    PubMed Central

    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

    2013-01-01

    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 PMID:23716558

  14. 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

  15. 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. PMID:26814595

  16. Induction of primary, antiviral cytotoxic, and proliferative responses with antigens administered via dendritic cells.

    PubMed Central

    Nair, S; Babu, J S; Dunham, R G; Kanda, P; Burke, R L; Rouse, B T

    1993-01-01

    Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating antigens is difficult to achieve. Exogenous antigens, such as viral proteins and peptides, normally induce CD4+ T-cell responses unless appropriately delivered to the major histocompatibility complex class I antigen presentation pathway. In vitro studies performed to address this issue revealed a similar scenario, and primary CTL induction with nonreplicating antigens has rarely been reported. This study demonstrated primary antiviral CTL induction in vitro with exogenous antigens delivered in vivo to dendritic cells. This study also evaluated the efficacy of glycoprotein B peptide (free or encapsulated in liposomes), peptide-tripalmitoyl-S-glyceryl cysteinyl conjugate (acylpeptide), and glycoprotein B protein encapsulated in pH-sensitive liposomes as antigen delivery vehicles. Our results show that higher levels of cytotoxicity against herpes simplex virus type 1 resulted from exposure of dendritic cells to peptide-tripalmitoyl-S-glyceryl cysteinyl in liposomes. Macrophages treated in a similar manner were not effective stimulators for primary CTL induction. Our data have relevance to the understanding of mechanisms of antigen processing and presentation and the design of antiviral vaccines. PMID:8510217

  17. Two new aliphatic lactones from the fruits of Coriandrum sativum L.

    PubMed Central

    2012-01-01

    Background The present paper describes the isolation and characterization of two new aliphatic δ-lactones along with three glycerides and n-nonadecanyl cetoleate from the fruits of Coriandrum sativum L. (Apiaceae). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions. Results Phytochemical investigation of the methanolic extract of C. sativum L. (Apiaceae) fruits resulted in the isolation of two new aliphatic δ-lactones characterized as 2α-n-heptatriacont-(Z)-3-en-1,5-olide (1) (coriander lactone) and 2α-n-tetracont-(Z,Z)-3,26-dien-18α-ol-1,5-olide (2) (hydroxy coriander lactone) together with glyceryl-1,2-dioctadec-9,12-dienoate-3-octadec-9-enoate (3); glyceryl-1,2,3-trioctadecanoate (4); n-nonadecanyl-n-docos-11-enoate (5) and oleiyl glucoside (6). Conclusions Phytochemical investigation of the methanolic extract of C. sativum gave coriander lactone and hydroxy coriander lactone as the new phytoconstituents. PMID:22800677

  18. Preparation and in vitro evaluation of salbutamol-loaded lipid microparticles for sustained release pulmonary therapy.

    PubMed

    Scalia, Santo; Salama, Rania; Young, Paul; Traini, Daniela

    2012-01-01

    The aim of this study was to prepare lipid microparticles (LMs) loaded with the polar bronchodilator agent salbutamol, and designed for sustained release pulmonary delivery. The microparticles were produced by melt emulsification followed by a sonication step, using different biocompatible lipid carriers (tristearin, stearic acid and glyceryl behenate) and phosphatidylcholine as the surfactant. The use of salbutamol free base, rather than salbutamol sulphate, was necessary to obtain the incorporation of the drug in the lipid particle matrix. The prolonged release of salbutamol base was achieved only by the glyceryl behenate microparticles (40.9% of encapsulated drug being released after 8 h). The salbutamol loading was 4.2% ± 0.1 and the mass median diameter, determined by laser diffraction, ranged from 4.8 to 5.4 µm. The sustained release of LMs were formulated as a carrier-free dry powder for inhalation and exhibited a fine particle fraction of 17.3% ± 2.2, as measured by multi-stage liquid impinger. PMID:22208706

  19. 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

  20. In vitro controlled release of colon targeted mesalamine from compritol ATO 888 based matrix tablets using factorial design

    PubMed Central

    Patel, J.K.; Patel, N.V.; Shah, S.H.

    2009-01-01

    A controlled release matrix formulation for mesalamine was designed and developed to achieve a 24 h release profile. Using compritol 888 ATO (glyceryl behenate) as an inert matrix-forming agent to control the release of mesalamine, formulation granules containing the solid dispersions were investigated. Pectin, a polysaccharide, was used as bacterial dependent polymer for colon targeting. The matrix tablets for these formulations were prepared by direct compression and their in vitro release tests were carried out. A 32 full factorial design was used for optimization by taking the amounts of glyceryl behenate (X1) and pectin (X2) as independent variables and percentage drug released at 2 (Q2), 16 (Q16) and 24 (Q24) h as dependent variables. Drug release from the matrix tablets formulations lasted for over 24 h. Images of the tablet surface and cross-section were characterized by scanning electron microscopy to show the formed pores and channels in the matrices. These may provide the release pathway for the inner embedded drugs. The co-mixing of polysaccharide pectin, into the waxy matrices played a meaningful role in targeting the tablets to colon. The drug release from the novel formulation may be attributed to the diffusion-controlled mechanism. The results of the full factorial design indicated that an optimum amount of compritol ATO 888 and a high amount of pectin favors the colon targeting and controlled release of mesalamine from dosage form. PMID:21589801

  1. 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. PMID:26314244

  2. Tackiness of acrylic and cellulosic polymer films used in the coating of solid dosage forms.

    PubMed

    Wesseling, M; Kuppler, F; Bodmeier, R

    1999-01-01

    The objective was to determine the tackiness of acrylic and cellulosic polymer films in order to make predictions on the tackiness (agglomeration) of coated dosage forms during coating and curing. Force-displacement curves of the detachment process of two polymeric films were used as a measure of tackiness. Various polymers (cellulosic (Aquacoat and acrylics (Eudragit RS 30D, L 30D, NE 30D)), plasticizers (triacetin, triethyl citrate, tributyl citrate, acetyltributyl citrate) and anti-tacking agents (talc and glyceryl monostearate) were investigated. The order of tackiness for films prepared from the different aqueous polymer dispersions was in order of Eudragit NE 30D > RS 30D > RL 30D > Aquacoat. The tackiness increased with increasing plasticizer concentration due to the softening of the polymer. A correlation between the minimum film formation temperature and the tackiness was observed, however, no correlation between the tackiness and the lipophilicity of the plasticizer was seen. Talc and glyceryl monostearate (GMS) reduced the tackiness of the films significantly, with GMS being effective at much lower concentrations. Curing of Eudragit RS 30D-coated theophylline beads at temperatures higher than 40 degrees C in an irreversible agglomeration of the beads and damage of the coating upon separation of the beads. This resulted in a faster release than with uncured beads. Blending the beads with talc just prior to the curing step eliminated the agglomeration and therefore film damage, even at a curing temperature of 60 degrees C. PMID:10234529

  3. Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.

    PubMed

    Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

    2013-01-01

    Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties. PMID:23923399

  4. Analysis of alcohols, as dimethylglycine esters, by electrospray ionization tandem mass spectrometry.

    PubMed

    Johnson, D W

    2001-03-01

    Dimethylglycine (DMG) esters are new derivatives for the rapid, sensitive and selective analysis of primary and secondary alcohols, in complex mixtures, by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their development was inspired by the use of the complementary dimethylaminoethyl esters for the trace, rapid analysis of fatty acids. DMG esters are simply prepared by heating a dichloromethane solution of the imidazolide of dimethylglycine, containing triethylamine, and an alcohol. DMG esters of long-chain fatty alcohols, isoprenoidal alcohols and hydroxy-acids are analysed by electrospray ionization tandem mass spectrometry with a precursor ion of m/z 104 scan. Diols, glyceryl esters, glyceryl ethers and some sterols are analysed by a neutral loss of 103 Da scan. Trimethylglycine (TMG) ester iodides, prepared by alkylation of DMG esters with methyl iodide, are more sensitive derivatives for molecules containing secondary alcohol groups, such as cholesterol and gibberellic acid. They are analysed by a precursor ion of m/z 118 scan. DMG or TMG derivatives were shown to be at least comparable and sometimes an order of magnitude more sensitive than N-methylpyridyl ether derivatives for ESI-MS/MS analysis of the different classes of alcohols. Applications of these derivatives for the diagnosis of inherited disorders and the analysis of natural products are presented. PMID:11312519

  5. Enhancing vitamin E bioaccessibility: factors impacting solubilization and hydrolysis of α-tocopherol acetate encapsulated in emulsion-based delivery systems.

    PubMed

    Yang, Ying; Decker, Eric Andrew; Xiao, Hang; McClements, David Julian

    2015-01-01

    Oil-soluble vitamins are often encapsulated within emulsion-based delivery systems to facilitate their incorporation into aqueous-based products. We have examined the influence of carrier oil type and simulated small intestinal fluid (SSIF) composition on the bioaccessibility of emulsified vitamin E using a gastrointestinal model. Oil-in-water emulsions containing vitamin E acetate were prepared using bile salts as emulsifier, and either long chain triacylglycerols (glyceryl trioleate, LCT) or medium chain triacylglycerols (glyceryl trioctanoate, MCT) as carrier oils. The addition of calcium (CaCl₂) to the SSIF increased the extent of lipid digestion in LCT-emulsions, but had little impact in MCT-emulsions. The bioaccessibility of vitamin E increased in the presence of calcium and phospholipids (DOPC) in LCT-emulsions, but decreased in MCT-emulsions. The highest bioaccessibility (≈66%) was achieved for LCT-emulsions when the SSIF contained both calcium and phospholipids. The conversion of α-tocopherol acetate to α-tocopherol after in vitro digestion was considerably higher for LCT-emulsions when calcium ions were present in the SSIF, but was not strongly affected by SSIF composition for MCT-emulsions. In general, this research provides important information about the factors influencing the bioaccessibility of emulsified vitamin E, which could be used to design more effective emulsion-based delivery systems for increasing the oral bioavailability of this important bioactive component. PMID:25312787

  6. A simple strategy to monitor lipase activity using liquid crystal-based sensors.

    PubMed

    Hu, Qiong-Zheng; Jang, Chang-Hyun

    2012-09-15

    In this study, we developed a simple label-free technique for monitoring the enzymatic activity of lipase using liquid crystal (LC)-based sensors. The optical response of LCs changed from a bright to dark appearance when an aqueous solution of lipase was in contact with a nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), that was doped with glyceryl trioleate, which is a glyceride that can be enzymatically hydrolyzed by lipase. Since the oleic acid released from the enzymatic reaction could spontaneously form a self-assembled monolayer at the aqueous/LC interface due to its amphiphilic property, the orientation of the LCs transited from a planar to homeotropic state, which induced a change in the optical response of the LCs. We did not observe a bright-to-dark shift in the optical appearance of LCs when pure 5CB was immersed into the lipase solution. Moreover, we further confirmed the specificity of the enzymatic reaction by transferring an aqueous buffer solution not containing an analyte, or with bovine serum albumin (BSA) or trypsin onto the interface of aqueous solutions and the glyceryl trioleate-doped 5CB, which did not produce any distinctive contrast in the optical appearance. These results suggest the feasibility of measuring the enzymatic activity of lipase using the LC-based sensing technique. Furthermore, our strategy could also be used for the preparation of a self-assembled monolayer of carboxylates at the aqueous/LC interface. PMID:22967518

  7. In vivo study of an instantly formed lipid-water cubic phase formulation for efficient topical delivery of aminolevulinic acid and methyl-aminolevulinate.

    PubMed

    Evenbratt, Hanne; Jonsson, Charlotte; Faergemann, Jan; Engström, Sven; Ericson, Marica B

    2013-08-16

    We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1g cubic phase in less than 1 min confirmed by X-ray diffraction, consisting of an ether lipid, 1-glyceryl monooleyl ether (GME), an aprotic solvent (propylene glycol or pentane-1,5-diol) and water. The efficacy of the cubic formulation was tested in vivo by administrating formulations containing 3% (w/w) of the HCl salts of δ-aminolevulinic acid (ALA) or methylaminolevulinate (MAL) to hairless mice. The endogenous formation of protoporphyrin IX (PpIX) was monitored spectrophotometrically as a marker for cellular uptake of active compound. As reference, a commercial product containing 16% (w/w) MAL in an oil-in-water emulsion (Metvix(®)), and a cubic phase based on an ester lipid (glyceryl monooleate, GMO), previously shown to facilitate topical delivery of both ALA and MAL, were applied. It was found that in general the cubic phases gave rise to higher fluorescence levels than the mice exposed to the commercial product. The instantly formed cubic formulations based on GME demonstrated the same efficiency as the GMO based formulations. The results imply that instantly formed cubic formulations opens up new opportunities, particularly for transdermal drug delivery of substances subject to stability problems in, e.g. aqueous environments. PMID:23727140

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

    PubMed

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

    2016-09-01

    This study describes for the first time the use of high-resolution nuclear magnetic resonance (NMR) on Klamath (Aphanizomenon flos-aquae, AFA) blue-green algae directly on powder suspension. These algae are considered to be a "superfood", due to their complete nutritional profile that has proved to have important therapeutic effects. The main advantage of NMR spectroscopy is that it permits the detection of a number of metabolites all at once. The Klamath alga metabolome was revealed to be quite complex, and the most peculiar phytochemicals that can be detected directly on algae by NMR are mycosporine-like amino acids (porphyra-334, P334; shinorine, Shi) and low molecular weight glycosides (glyceryl β-d-galactopyranoside, GalpG; glyceryl 6-amino-6-deoxy-α-d-glucopyranoside, ADG), all compounds with a high nutraceutical value. The presence of cis-3,4-DhLys was revealed for the first time. This molecule could be involved in the anticancer properties ascribed to AFA. PMID:27537083

  9. Nanomicelle Based Peroral Delivery System for Enhanced Absorption and Sustained Release of 10-Hydrocamptothecin.

    PubMed

    Tian, Ye; Shi, Chenjun; Zhang, Xin; Sun, Yujiao; Wang, Juan; Zhang, Yuyang; Yang, Jingyu; Wang, Lihui; Wang, Linlin; Mao, Shirui

    2015-02-01

    An effective sustained-release peroral drug delivery system is needed for chemotherapy. Here, we show that such a system can be achieved by designing polymeric nanomicelles combining mucoadhesion, enhanced absorption and controlled release. Chitosan and glyceryl-monooleate have many desirable properties, so we synthesized a novel chitosan derivative, chitosan-conjugated glyceryl monooleate. We loaded 10-hydroxycamptothecin (HCPT) into the cores of nanomicelles by pH-coacervation, which significantly improved drug loading and stability. We studied the pharmacokinetics of these drug-loaded nanomicelles, and they demonstrated remarkably prolonged circulation time in vivo up to 72 h. Orally administered HCPT-loaded nanomicelles also showed comparable antitumor effects and smaller changes in body weight compared to HCPT administered by injection. Most importantly, by using in vivo pharmacokinetic and pharmacodynamic studies, we showed that comparable antitumor effects can be achieved by peroral administration of HCPT-loaded nanomicelles every three days, and that the nanomicelles had less severe side effects. In vivo imaging provided direct evidence that the micelles were absorbed and exhibited sustained release after oral administration. These results indicate a promising future for nanomicelle-based peroral drug delivery as a superior alternative to injection, and they also provide guiding principles for designing amphiphilic copolymers. PMID:26349302

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

    PubMed

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

    2015-12-28

    A gene encoding lipolytic enzyme, lip7-3, was isolated from Bacillus sp. W130-35 isolated from a tidal mud flat. The gene encoded a protein of 215 amino acids with a signal peptide composed of 34 amino acid residues. Lip7-3 belonged to the family I.4 lipase and showed its maximal activity at pH 9.0 and 60°C. Its activity increased in the presence of 30% methanol and, remarkably, increased as well to 154.6% in the presence of Ca(2+). Lip7-3 preferred pnitrophenyl octanoate (C8) as a substrate and exhibited broad specificity for short- to longchain fatty acid esters. Additionally, Lip7-3 showed a low degree of enantioselectivity for an S-enantiomer (e.g., (S)-methyl-3-hydroxy-2-methylpropionate). It efficiently hydrolyzed glyceryl tributyrate, but did not hydrolyze glyceryl trioleate, fish oil, or olive oil. Its substrate specificity and activation by the solvent might offer a merit to the biotechnological enzyme applications like transesterification in the production of biodiesel. PMID:26370800

  11. Inability of two topical treatments to influence the course of experimentally induced dermatophytosis in cats.

    PubMed

    DeBoer, D J; Moriello, K A

    1995-07-01

    An experimental model of dermatophytosis was used to compare the efficacy of 2 topical antifungal treatments against Microsporum canis infection in cats. Infection was established in 24 cats by topical application of 10(5) M canis macroconidia to the skin of the lateral part of the abdomen under an occlusive bandage. Three groups of 6 cats each then were treated twice weekly for 18 weeks with chlorhexidine shampoo and dip, detergent shampoo vehicle only, or glyceryl monolaurate shampoo. Six cats were left untreated as controls. The experimentally induced infections strongly resembled naturally developing infections of moderate to severe nature. Signs of infection peaked in severity at 5 weeks after inoculation, then gradually resolved over 7 to 16 additional weeks. Dermatophytes were consistently isolated on culture for at least 8 weeks of treatment. Mycologic cure (defined as lack of dermatophyte isolation on 3 successive weekly cultures) was attained in 8 cats at the end of 18 weeks of treatment. Infections appeared to resolve at equivalent rates in all groups of cats, including controls. Consistent or meaningful significant differences in variables such as lesion size, clinical sign score, or total infection score were not found between treated and control groups. Our study revealed that this topical treatment regimen with chlorhexidine or glyceryl monolaurate is ineffective against M canis infection in cats. PMID:7601693

  12. 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.

  13. Flavonolignans and other constituents from Lepidium meyenii with activities in anti-inflammation and human cancer cell lines.

    PubMed

    Bai, Naisheng; He, Kan; Roller, Marc; Lai, Ching-Shu; Bai, Lu; Pan, Min-Hsiung

    2015-03-11

    From the roots of Lepidium meyenii Walpers (Brassicaceae) have been isolated and identified 2 flavonolignans, tricin 4'-O-[threo-β-guaiacyl-(7″-O-methyl)-glyceryl] ether (1) and tricin 4'-O-(erythro-β-guaiacyl-glyceryl) ether (2), along with 11 other known compounds, tricin (3), pinoresinol (4), 4-hydroxycinnamic acid (5), guanosine (6), glucotropaeolin (7), desulfoglucotropaeolin (8), 3-hydroxybenzylisothiocyanate (9), malic acid benzoate (10), 5-(hydroxymethyl)-2-furfural (11), d-phenylalanine (12), and vanillic acid 4-O-β-d-glucoside (13). Structures were elucidated on the basis of NMR and MS data. Some isolates and previously isolated lepidiline B (14) were tested for cytotoxicity in a small panel of human cancer cell lines (Hep G2, COLO 205, and HL-60) and for anti-inflammatory activities in LPS-treated RAW 264.7 macrophage. Among them, compounds 1 and 14 were modestly active for inhibiting nitrite production in macrophage. Compounds 1, 14, and 3 were demonstrated to be selectively active against HL-60 cells with IC50 values of 40.4, 52.0, and 52.1 μM, respectively. PMID:25667964

  14. 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.

  15. Lipid microparticles as sustained release system for a GnRH antagonist (Antide).

    PubMed

    Del Curto, M D; Chicco, D; D'Antonio, M; Ciolli, V; Dannan, H; D'Urso, S; Neuteboom, B; Pompili, S; Schiesaro, S; Esposito, P

    2003-04-29

    Lipid microparticles (LMs) as a sustained release system for a gonadotropin release hormone (GnRH) antagonist (Antide) were prepared and evaluated. Antide loaded microparticles (Antide-LMs) were obtained by a cryogenic micronization process starting from two different monoglycerides (glyceryl monobehenate and glyceryl monostearate) and using two different incorporation methods (co-melting and solvent evaporation). Antide-LMs, 2% (w/w) loading, were characterized for drug incorporation by RP-HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy. In vitro peptide release and in vitro biological activity were also studied. Serum Antide and testosterone levels, as pharmacodynamic marker, were assessed following subcutaneous administration in rats. Antide-LMs showed a mean diameter of approximately 30 micro m and variable Antide release depending on lipid matrix and incorporation method. In vivo experiments demonstrated that detectable Antide plasma levels were present, in the case of Antide-LMs based on Compritol E ATO obtained by co-melting procedure, for at least 30 days after dosing. Testosterone levels were consistent with prolonged pharmacokinetic profiles. In vitro release of Antide from LMs correlated well with the in vivo release. In conclusion, LMs can sustain the release of Antide for at least 1 month. The levels of the initial 'burst' and the extent of the pharmacodynamic effect can be influenced by the lipid characteristics and by process conditions. PMID:12711452

  16. Combustion of liquid fuel in the counter-swirled jets of a gas turbine plant annular combustion chamber

    NASA Astrophysics Data System (ADS)

    Tumanovskii, A. G.; Semichastnyi, N. N.; Sokolov, K. Iu.

    1986-03-01

    Tests were carried out on an annular combustion chamber rig with a stabilizer of the type used in the GTN-25 gas turbine plant to determine the feasibility of burning a liquid fuel (diesel fuel, GOST 4749-73) in a combustion chamber of this type. Very high performance was obtained for a number of important characteristics of the microflame combustion process in counterswirled jets where all the air was supplied through the front unit of the chamber. However, the tests did not make it possible to solve some of the problems which arise when operating under full-scale conditions, such as the required high combustion efficiency under variable operating conditions of a gas turbine plant; elimination of soot formation at the walls of the stabilizer and the internal surfaces of the pipes supplying fuel to the atomizers; and a decrease in smoking under conditions of excess air factor.

  17. Genetic analysis of the freshwater crayfish Cherax tenuimanus.

    PubMed

    Imgrund, J; Groth, D; Wetherall, J

    1997-08-01

    The marron (Cherax tenuimanus) is one of the few species of freshwater crayfish native to Australia that is suitable for aquaculture and occurs only in the southwest of Western Australia. This study describes polymorphic microsatellite markers which differentiate marron populations from several geographically distinct regions (including rivers and streams, dams, and commercial marron farms) throughout Western Australia. Twenty microsatellite loci, primarily of the (CA)n. (GT)n type, were isolated and sequenced from a marron cosmid library. Three of these loci were characterised further. Two loci exhibited extensive polymorphism and one was monomorphic. The polymorphic loci exhibited Mendelian codominant inheritance in the family group comprising two individual parents and approximately 100 offspring bred for this study. These loci permitted differentiation between the five geographically distinct populations studied and thus provide a basis for genetic characterisation of marron stock in Western Australia. PMID:9378141

  18. 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.

  19. Abnormal Presentation of Choriocarcinoma and Literature Review

    PubMed Central

    Yousefi, Zohreh; Mottaghi, Mansorhe; Rezaei, Alireza; Ghasemian, Sedighe

    2016-01-01

    Introduction Gestational trophoblastic neoplasms have highly been malignant potential, which usually occurred in child-bearing age women. Unusual feature of this malignancy would be rare, it was important to take in mind the possibility of GTN in different manifestation. Based on the above mentioned, the aim of this presentation would be the management and outcome of a case series of choriocarcinoma patients with abnormal manifestation. Case Presentation We have presented four patients, first who initially manifestation with signs of septic shock, the second case with severe gastrointestinal hemorrhage, the third case with postpartum infection and the forth case was a postmenopausal bleeding patient. Conclusions In case of metastatic choriocarcinoma with precise history, accurate diagnosis and appropriate treatment have led us to curable results. PMID:27482332

  20. Microsatellite instability in bladder cancer.

    PubMed

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, K

    1993-12-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chromosome for three tumors. Single locus alterations were detected in three tumors, while three other tumors revealed changes in two or more loci. In one tumor we found microsatellite instability in all five loci analyzed on chromosome 9. The alterations detected were either minor 2-base pair changes or larger (> 2 base pairs) alterations in repeat length. All six tumors were low stage (Ta-T1), suggesting that these alterations can occur early in bladder tumorigenesis. PMID:8242615

  1. 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

  2. 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.

    2016-06-01

    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.

  3. 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. PMID:26445013

  4. 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.

  5. 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.

  6. An Investigative Study into Psychological and Fertility Sequelae of Gestational Trophoblastic Disease: The Impact on Patients’ Perceived Fertility, Anxiety and Depression

    PubMed Central

    Di Mattei, Valentina E.; Carnelli, Letizia; Bernardi, Martina; Pagani Bagliacca, Elena; Zucchi, Paola; Lavezzari, Luca; Giorgione, Veronica; Ambrosi, Alessandro; Mangili, Giorgia; Candiani, Massimo; Sarno, Lucio

    2015-01-01

    Objectives Gestational Trophoblastic Disease (GTD) comprises a group of disorders that derive from the placenta. Even if full recovery is generally expected, women diagnosed with GTD have to confront: the loss of a pregnancy, a potentially life-threatening diagnosis and delays in future pregnancies. The aim of the study is to evaluate the psychological impact of GTD, focusing on perceived fertility, depression and anxiety. Methods 37 patients treated for GTD at San Raffaele Hospital, Milan, took part in the study. The STAI-Y (State-Trait Anxiety Inventory), the BDI-SF (Beck Depression Scale-Short Form) and the FPI (Fertility Problem Inventory) were used. Patients were grouped on the basis of presence of children (with or without), age (< or ≥35) and type of diagnosis (Hydatidiform Mole, HM, or Gestational Trophoblastic Neoplasia, GTN). Differences in the values between variables were assessed by a t-type test statistic. Three-way ANOVAs were also carried out considering the same block factors. Results The study highlights that women suffering from GTN had higher depression scores compared to women suffering from HM. A significant correlation was found between anxiety (state and trait) and depression. Younger women presented higher Global Stress scores on the FPI, especially tied to Need for Parenthood and Relationship Concern subscales. Need for Parenthood mean scores significantly varied between women with and without children too. Conclusions We can conclude that fertility perception seems to be negatively affected by GTD diagnosis, particularly in younger women and in those without children. Patients should be followed by a multidisciplinary team so as to be supported in the disease’s psychological aspects too. PMID:26030770

  7. An association study between Heme oxygenase-1 genetic variants and Parkinson's disease

    PubMed Central

    Ayuso, Pedro; Martínez, Carmen; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Luengo, Antonio; Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; Agúndez, José A. G.; García-Martín, Elena

    2014-01-01

    The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT)n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT)n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk. PMID:25309329

  8. 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

  9. Early prediction of treatment resistance in low-risk gestational trophoblastic neoplasia using population kinetic modelling of hCG measurements

    PubMed Central

    You, B; Harvey, R; Henin, E; Mitchell, H; Golfier, F; Savage, P M; Tod, M; Wilbaux, M; Freyer, G; Seckl, M J

    2013-01-01

    Background: In low-risk gestational trophoblastic neoplasia (GTN) patients, a predictive marker for early identification of methotrexate (MTX) resistance would be useful. We previously demonstrated that kinetic modelling of human chorionic gonadotrophin (hCG) measurements could provide such a marker. Here we validate this approach in a large independent patient cohort. Methods: Serum hCG measurements of 800 low-risk GTN patients treated with MTX were analysed. The cohort was divided into Model and Test data sets. hCG kinetics were described from initial treatment day to day 50 using: ‘(hCG(time))=hCG0*exp(–k*time)+hCGres', where hCGres is the modelled residual production, hCG0 is the baseline hCG level, and k is the rate constant. HCGres-predictive value was investigated against previously reported predictors of MTX resistance. Results: Declining hCG measurements were well fitted by the model. The best discriminator of MTX resistance in the Model data set was hCGres, categorised by an optimal cut-off value of >20.44 IU l−1: receiver-operating characteristic (ROC) area under the curve (AUC)=0.87; Se=0.91; Sp=0.83. The predictive value of hCGres was reproducible using the Test data set: ROC AUC=0.87; Se=0.88; Sp=0.86. Multivariate analyses revealed hCGres as a better predictor of MTX resistance (HR=1.01, P<0.0001) and MTX failure-free survival (HR=13.25, P<0.0001) than other reported predictive factors. Conclusion: hCGres, a modelled kinetic parameter calculated after fully dosed three MTX cycles, has a reproducible value for identifying patients with MTX resistance. PMID:23591194

  10. Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative inactivation.

    PubMed

    Schmidt, Kurt; Neubauer, Andrea; Kolesnik, Bernd; Stasch, Johannes-Peter; Werner, Ernst R; Gorren, Antonius C F; Mayer, Bernd

    2012-09-01

    Tetrahydrobiopterin (BH4) is a major endogenous vasoprotective agent that improves endothelial function by increasing nitric oxide (NO) synthesis and scavenging of superoxide and peroxynitrite. Therefore, administration of BH4 is considered a promising therapy for cardiovascular diseases associated with endothelial dysfunction and oxidative stress. Here we report on a novel function of BH4 that might contribute to the beneficial vascular effects of the pteridine. Treatment of cultured porcine aortic endothelial cells with nitroglycerin (GTN) or 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) resulted in heme oxidation of soluble guanylate cyclase (sGC), as evident from diminished NO-induced cGMP accumulation that was paralleled by increased cGMP response to a heme- and NO-independent activator of soluble guanylate cyclase [4-([(4-carboxybutyl)[2-(5-fluoro-2-([4'-(trifluoromethyl)biphenyl-4-yl]methoxy)phenyl)ethyl]amino]methyl)benzoic acid (BAY 60-2770)]. Whereas scavenging of superoxide and/or peroxynitrite with superoxide dismutase, tiron, Mn(III)tetrakis(4-benzoic acid)porphyrin, and urate had no protective effects, supplementation of the cells with BH4, either by application of BH4 directly or of its precursors dihydrobiopterin or sepiapterin, completely prevented the inhibition of NO-induced cGMP accumulation by GTN and ODQ. Tetrahydroneopterin had the same effect, and virtually identical results were obtained with RFL-6 fibroblasts, suggesting that our observation reflects a general feature of tetrahydropteridines that is unrelated to NO synthase function and not limited to endothelial cells. Protection of sGC against oxidative inactivation may contribute to the known beneficial effects of BH4 in cardiovascular disorders associated with oxidative stress. PMID:22648973

  11. 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

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

    PubMed

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

    2016-12-01

    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

  13. 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

  14. 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. PMID:26498372

  15. 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.

  16. Isolation and identification of new phytoconstituents from the fruit extract of Amomum subulatum Roxb.

    PubMed

    Kumar, Gopal; Chauhan, Baby; Ali, Mohammed

    2014-01-01

    The fruits of Amomum subulatum Roxb. (Zingiberaceae) (large cardamom), cultivated in the northern Himalayas, are used to treat stomach disorders, pulmonary diseases and liver complaints. Phytochemical investigation of the fruits led to the isolation of four new chemical compounds characterised as geranil-3(10)-en-9-olyl octadec-9-enoate, geranil-3(10)-en-9-carboxyl-β-D-arabinopyranoside, geranilan-9-carboxy-α-L-arabinopyranoside and stigmast-5-en-3β-ol-3β-D-arabinopyranosyl-2'-(3″-methoxy) benzoate-3'-octadec-9‴,12‴,15‴-trienoate, along with the known compounds oleodilinolein and glyceryl trilinoleniate on the basis of spectral data analysis. PMID:24274834

  17. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique.

    PubMed

    Trotta, Michele; Debernardi, Francesca; Caputo, Otto

    2003-05-12

    A preparation method for nanoparticles based on the emulsification of a butyl lactate or benzyl alcohol solution of a solid lipid in an aqueous solution of different emulsifiers, followed by dilution of the emulsion with water, was used to prepare glyceryl monostearate nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 47+/-2 degrees C and in order to reach submicron size a high-shear homogenizer was used. Particle size of the solid lipid nanoparticles (SLN) was affected by using different emulsifiers and different lipid loads. By using lecithin and taurodeoxycholic acid sodium salt, on increasing the GMS percentage from 2.5 to 10% an increase of the mean diameter from 205 to 695 nm and from 320 to 368nm was observed for the SLN prepared using benzyl alcohol and butyl lactate, respectively. Transmission electron micrographs of SLN reveal nanospheres with a smooth surface. PMID:12711170

  18. 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. PMID:2432953

  19. Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles.

    PubMed

    Durand, L; Habran, N; Henschel, V; Amighi, K

    2010-01-01

    The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310 nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2 h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC. PMID:21034364

  20. Effect of hydrophilic substances on liberation of quinidine from starch - alginate sphere.

    PubMed

    Kasperek, R; Czarnecki, W

    2001-01-01

    The effect of selected hydrophilic agents on the quinidine loading and its release from potato starch alginate spheres prepared by instilling viscous suspensions into a desolvation liquid (saturated calcium chloride: paraffin liquid: heptan 1:1:1 v/v/v) was studied. The loading of quinidine in spheres was 59.77%-46.30% and it depended on the presence of auxiliary hydrophillic agents such as polyethylene glycol 2000 (59.77%), polyoxyethylene - 20 - sorbitan monostearate (49.55%), glyceryl monostearate (49.02%), sorbitan monooleate (46.30%). The drug release from spheres was diffusion controlled in accordance with the Higuchi model. It was concluded that the release rate constants depended on the drug - carrier - hydrophilic agent composition and dissolution media. PMID:11501786

  1. α-Tocopherol impact on oxy-radical induced free radical decomposition of DMSO: Spin trapping EPR and theoretical studies

    NASA Astrophysics Data System (ADS)

    Jerzykiewicz, Maria; Ćwieląg-Piasecka, Irmina; Witwicki, Maciej; Jezierski, Adam

    2011-05-01

    EPR spin trapping and theoretical methods such as density functional theory (DFT) as well as combined DFT and quadratic configuration interaction approach (DFT/QCISD) were used to identify the radicals produced in the reaction of oxy-radicals and dimethyl sulfoxide (DMSO) in the presence and absence of α-tocopherol. Additionally, the mixtures of α-tocopherol with linolenic acid and glyceryl trilinoleate as well as bioglycerols (glycerol fractions from biodiesel production) were tested. α-Tocopherol inhibited oxidation of the main decomposition product of DMSO, •CH 3 to •OCH 3 but did not prevent the transformation process of N-t-butyl- α-phenylnitrone (PBN) into 2-methyl-2-nitrosopropane (MNP). Theoretical investigations confirmed the structures of proposed spin adducts and allowed to correlate the EPR parameters observed in the experiment with the spin adducts electronic structure.

  2. Synthesis of ethers by GaBr3 -catalyzed reduction of carboxylic acid esters and lactones by siloxanes.

    PubMed

    Biermann, Ursula; Metzger, Jürgen O

    2014-02-01

    Ethers were synthesized by reduction of the respective esters catalyzed by gallium bromide (GaBr3 ) and using siloxanes, preferentially 1,1,3,3-tetramethyldisiloxane, as reductant. Methyl oleate, triglycerides, that is, tributyrine and glyceryl triundec-10-enoate as well as γ- and δ-lactones were converted into the respective ethers in high to moderate yields. γ-Lactones were reduced with high selectivity in the presence of a methyl ester functionality. The reduction has been carried out at room temperature or moderately elevated temperature of up to 60 °C using stoichiometric amounts of the reductant and 0.005-0.01 equiv of GaBr3 as catalyst per ester functionality without any solvent added. After a reaction time of 1-4 h the conversion of the substrate was 100 %. The product was separated from polymeric siloxanes formed as coupled product by simple distillation. PMID:24488681

  3. [Allergic contact dermatitis in beauty parlor clients].

    PubMed

    Gottlöber, P; Gall, H; Bezold, G; Peter, R U

    2001-05-01

    Occupational contact dermatitis in hair dressers and beauticians has increased in importance in the past years. Type IV-allergies against glyceryl monothioglycate components of permanent waves are most common. Other occupational allergens include bleach components such as ammonium persulfate and hair dye ingredients such as p-phenylenediamine (PPD) and p-toluylene-diamine (PTD) base. Allergies to hair dyes in customers of hair dressers have rarely been observed. Two female patients developed allergic contact dermatitis of the scalp and face after repeated use of Polycolor intensivtönung schwarz and of Movida color. We also review the current literature on type IV-allergies to components of hair dressing products components. PMID:11405157

  4. An unusual dehydratase acting on glycerate and a ketoreducatse stereoselectively reducing α-ketone in polyketide starter unit biosynthesis.

    PubMed

    He, Hai-Yan; Yuan, Hua; Tang, Man-Cheng; Tang, Gong-Li

    2014-10-13

    Polyketide synthases (PKSs) usually employ a ketoreductase (KR) to catalyze the reduction of a β-keto group, followed by a dehydratase (DH) that drives the dehydration to form a double bond between the α- and β-carbon atoms. Herein, a DH*-KR* involved in FR901464 biosynthesis was characterized: DH* acts on glyceryl-S-acyl carrier protein (ACP) to yield ACP-linked pyruvate; subsequently KR* reduces α-ketone that yields L-lactyl-S-ACP as starter unit for polyketide biosynthesis. Genetic and biochemical evidence was found to support a similar pathway that is involved in the biosynthesis of lankacidins. These results not only identified new PKS domains acting on different substrates, but also provided additional options for engineering the PKS starter pathway or biocatalysis. PMID:25160004

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

    PubMed

    Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul

    2014-06-01

    A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes. PMID:24613489

  6. Microemulsion formed by alkyl polyglucoside and an alkyl glycerol ether with weakly charged films.

    PubMed

    Fukuda; Olsson; Ueno

    2001-02-01

    We have studied the effects on phase equilibria of a nonionic surfactant mixture-water-oil system when replacing small amount of surfactant molecules by ionic surfactant, sodium dodecyl sulfate (SDS). The nonionic surfactant system contains dodecyl-beta-D-maltoside (C(12)AG2) and iso-octyl glyceryl ether (i-C(8)GE) as cosurfactant, water and cyclohexane at constant water to oil ratio of 60/40 (w/w). Adding a small amount of SDS has large impact on the phase behavior. Clear liquid crystalline phase and upper microemulsion phase are added to the phase sequence at high i-C(8)GE/(C(12)AG2+i-C(8)GE) ratio. We also compare the phase equilibria of pure dodecyl maltoside system with polyglucosides mixture system. PMID:11087985

  7. Modeling accelerated and decelerated drug release in terms of fractional release rate.

    PubMed

    Weiss, Michael

    2015-02-20

    The model of a proportional change in fractional dissolution rate was used to quantify influences on the vitro dissolution process. After fitting the original dissolution profile with an empirical model (inverse Gaussian distribution), acceleration and deceleration effects due to dissolution conditions or formulation parameters could be described by one parameter only. Acceleration of dissolution due to elevated temperature and deceleration by increasing the content of glyceryl monostearate in theophylline tablets are presented as examples. Likewise, this approach was applied to in vitro-in vivo correlation (IVIVC). It is shown that the model is appropriate when the plot of the in vivo versus in vivo times is nonlinear and can be described by a power function. The results demonstrate the utility of the model in dissolution testing and IVIVC assessment. PMID:25486334

  8. Ca3 (PO4 )2 :Eu3+ phosphor preparation with different morphologies and their fluorescence properties.

    PubMed

    Zhou, Xiaochun; Wang, Xiaojun

    2014-03-01

    Ca3(PO4)2:Eu(3+) phosphor was prepared using a facile chemistry method in the presence of surfactants. The effects of surfactants on the morphology and photoluminescence properties of Ca3(PO4)2:Eu(3+) phosphor were investigated. The morphology of the phosphor was significantly influenced by the surfactants employed. When nonionic surfactant glyceryl monostearate and anionic surfactant sodium dodecylbenzene sulfonate were employed, the phosphor powders are composed of a large number of homogeneous spherical particles with sizes of 0.3-0.6 µm and 2-3 µm, respectively. By contrast, when cationic surfactant cetyltrimethylammonium bromide was used, the morphology of the phosphor is completely different. The product is an excellent cuboid, and the phosphor prepared with 2.5 mmol cetyltrimethylammonium bromide showed higher luminescent intensity than phosphors prepared with the other two types of surfactants. PMID:23616256

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

    PubMed

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

    2013-11-01

    A new naphtho[1,2-b]furan, 2,9-dihydroxy-7-methoxy-4-methylnaphtha[1,2-b]furan-3(2H)-one (1), along with 10 known compounds vanillic acid (2), naringenin (3), glyceryl-1-tetracosanoate (4), moracin J (5), 1,3,8-trihydroxyanthraquinone (6), esculetin (7), mauritianin (8), kaempferol 3-neohesperidoside (9), β-sitosterol (10), and β-daucosterol (11), was isolated from the leaves of Cassia fistula. The structure of the new compound was determined by NMR and X-ray analysis. Compounds 1, 3, 5-9 were isolated from this plant for the first time. The naphtha[1,2-b]furan was firstly isolated from the natural resources. PMID:23822190

  10. Interannual variations in the lipids of the Antarctic pteropods Clione limacina and Clio pyramidata.

    PubMed

    Phleger, C F; Nelson, M M; Mooney, B D; Nichols, P D

    2001-03-01

    Antarctic pteropods, Clione limacina (Order Gymnosomata) and Clio pyramidata (order Thecosomata), were collected near Elephant Island, South Shetland Islands, during 1997 and 1998. Total lipid was high in C. limacina (29--36 mg g(-1) wet mass) and included 46% of diacy1glyceryl ether (DAGE, as % of total lipid) for both 1997 and 1998. DAGE was not detected in C. pyramidata, which had mainly polar lipid and triacy1glycerol. 1-O-Alkyl glyceryl ethers (GE) derived from the DAGE consisted primarily of 15:0 and 16:0, with lower 17:0 and a17:0. The principal sterols of both pteropods included trans-dehydrocholesterol, brassicasterol, 24-methylenecholesterol, cholesterol and desmosterol. Levels of 24-methylenecholesterol and desmosterol were lower in both pteropods in 1997 compared to 1998. C. limacina had high levels of the odd-chain fatty acids 17:1(n--8)c and 15:0 in contrast to C. pyramidata. The previously proposed source of elevated odd-chain fatty acids in C. limacina is via propionate derived from phytoplankton DMPT; another possible source may be from thraustochytrids, which are common marine microheterotrophs. C. pyramidata had twice as much PUFA as C. limacina, largely due to higher 20:5(n--3). The PUFA 18:5(n--3) and very long chain fatty acids (C(24), C(26) and C(28) VLC-PUFA) were only detected in 1998 pteropods. In comparison, 1996 samples of C. limacina contained lower DAGE levels, which also may reflect differences in diet and oceanographic conditions. Interannual variations in specific lipid biomarkers are discussed with respect to possible different phytoplankton food sources available in the AMLR survey area. PMID:11250551

  11. 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

  12. Abiotic Condensation Synthesis of Glyceride Lipids and Wax Esters Under Simulated Hydrothermal Conditions

    NASA Astrophysics Data System (ADS)

    Rushdi, Ahmed I.; Simoneit, Bernd R. T.

    2006-04-01

    Precursor compounds for abiotic proto cellular membranes are necessary for the origin of life. Amphipathic compounds such as fatty acids and acyl glycerols are important candidates for micelle/bilayer/vesicle formation. Two sets of experiments were conducted to study dehydration reactions of model lipid precursors in aqueous media to form acyl polyols and wax esters, and to evaluate the stability and reactions of the products at elevated temperatures. In the first set, mixtures of n-nonadecanoic acid and ethylene glycol in water, with and without oxalic acid, were heated at discrete temperatures from 150 ∘C to 300 ∘C for 72 h. The products were typically alkyl alkanoates, ethylene glycolyl alkanoates, ethylene glycolyl bis-alkanoates and alkanols. The condensation products had maximum yields between 150 ∘C and 250 ∘C, and were detectable and thus stable under hydrothermal conditions to temperatures < 300 ∘C. In the second set of experiments, mixtures of n-heptanoic acid and glycerol were heated using the same experimental conditions, with and without oxalic acid, between 100 ∘C and 250 ∘C. The main condensation products were two isomers each of monoacylglycerols and diacylglycerols at all temperatures, as well as minor amounts of the fatty acid anhydride and methyl ester. The yield of glyceryl monoheptanoates generally increased with increasing temperature and glyceryl diheptanoates decreased noticeably with increasing temperature. The results indicate that condensation reactions and abiotic synthesis of organic lipid compounds under hydrothermal conditions occur easily, provided precursor concentrations are sufficiently high.

  13. IN VITRO ORGANIC NITRATE BIOACTIVATION TO NITRIC OXIDE BY RECOMBINANT ALDEHYDE DEHYDROGENASE 3A1

    PubMed Central

    Lin, Shunxin; Page, Nathaniel A.; Fung, Sun Mi; Fung, Ho-Leung

    2013-01-01

    Organic nitrates (ORNs) are commonly used anti-ischemic and anti-anginal agents, which serve as an exogenous source of the potent vasodilator nitric oxide (NO). Recently, both mitochondrial aldehyde dehydrogenase-2 (ALDH2) and cytosolic aldehyde dehydrogenase-1a1 (ALDH1A1) have been shown to exhibit the ability to selectively bioactivate various ORNs in vitro. The objective of the present research was to examine the potential role of ALDH3A1, another major cytosolic isoform of ALDH, in the in vitro bioactivation of various ORNs, and to estimate the enzyme kinetic parameters toward ORNs through mechanistic modeling. The extent of bioactivation was assayed by exposing recombinant ALDH3A1 to various concentrations of ORNs, and measuring the concentration-time profiles of released NO via a NO-specific electrode. Metabolite formation kinetics was monitored for nitroglycerin (NTG) using LC/MS/MS. Our results showed that ALDH3A1 mRNA and protein were highly expressed in C57BL/6 mouse aortic, cardiac, and hepatic tissues, and it was able to release NO from several ORNs, including NTG, isosorbide dinitrate (ISDN), isosorbide-2-mononitrate (IS-2-MN), and nicorandil with similar Vmax (0.175 – 0.503 nmol/min/mg of ALDH3A1), and Km values of 4.01, 46.5, 818 and 5.75 × 103 μM respectively. However, activation of isosorbide-5-mononitrate (IS-5-MN) by ALDH3A1 was undetectable in vitro. ALDH3A1 was also shown to denitrate NTG, producing primarily glyceryl 1, 2-dinitrate (1, 2-GDN) in preference to glyceryl 1, 3-dinitrate (1, 3-GDN). Therefore, ALDH3A1 may contribute to the bioactivation of ORNs in vivo. PMID:24126018

  14. 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

  15. 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. PMID:25681745

  16. 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. PMID:26980237

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

    PubMed

    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/cm(2), feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules. PMID:27222612

  18. 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.

  19. Explosion and Ion Association Chemistry of the Anion Radicals of 2,4,6-Trinitrotoluene, 2,6-Dinitrotoluene, and Trinitrobenzene.

    PubMed

    Batz, Matthew L.; Garland, Paul M.; Reiter, Richard C.; Sanborn, Michael D.; Stevenson, Cheryl D.

    1997-04-01

    EPR analysis shows that the anion radical of 2,6-dinitrotoluene (DNT) in liquid ammonia exists with the counterion (either K(+) or Na(+)) associated with one of the two nitro groups. This tight association (-NO(2)(*-)M(+)) persists after solvent removal, and it renders the anion radical very susceptible to loss of metal nitrite. The slightest agitation of the solid potassium salt of DNT(*-) leads to detonation, and formation of KNO(2) and polymer (in the solid phase) and CH(4), HCN, H(2), and N(2)O (in the gas phase). Trapping experiments suggest that the methane comes from carbenes, and it is suggested that the HCN comes from an anthranil radical intermediate. The potassium anion radical salts of 1,3-dinitrobenzene, 2,6-dinitrotoluene, 1,3,5-trinitrobenzene, and 2,4,6-trinitrotoluene all readily lose KNO(2), and the ease of C-NO(2)(*-)M(+) bond rupture increases with the degree of nitration. In the cases of the two trinitrated systems dissociation takes place immediately upon anion radical formation in liquid ammonia. This observation is consistent with the fact that only the systems with two nitro groups vicinal to a methyl group yield HCN upon detonation. PMID:11671508

  20. 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.

  1. 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

  2. Migration kinetics and mechanisms of plasticizers, stabilizers at interfaces of NEPE propellant/HTPB liner/EDPM insulation.

    PubMed

    Huang, Zhi-ping; Nie, Hai-ying; Zhang, Yuan-yuan; Tan, Li-min; Yin, Hua-li; Ma, Xin-gang

    2012-08-30

    Migration appeared in the interfaces of nitrate ester plasticized polyether (NEPE) based propellant/hydroxyl-terminated polybutadiene (HTPB) based liner/ethylene propylene terpolymer (EPDM) based insulation was studied by aging at different temperatures. The migration components were extracted with solvent and determined by high performance liquid chromatography (HPLC). The migration occurred within 1mm to the interfaces, and the apparent migration activation energy (Ea) of nitroglycerin (NG), 1,2,4-butanetriol trinitrate (BTTN) and a kind of aniline stabilizer AD in propellant, liner and insulation was calculated respectively on the basis of HPLC data. The Ea values were among 15 and 50 kJ/mol, which were much less than chemical energy, and almost the same as hydrogen bond energy. The average diffusion coefficients were in the range of 10(-19)m(2)s(-1) to 10(-16)m(2)s(-1). It seemed the faster the migration rates, the smaller the apparent migration activation energy, the larger the diffusion coefficient and the less the amount of migration. It could be explained that the migration rate and energy were affected by the molecular volume of a mobile component and its diffusion property, and the amount of migration was resulted from the molecular polarity comparability of a mobile component to the based material. PMID:22727260

  3. 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. PMID:25995854

  4. [Long-term effect of organic nitrates in angina pectoris: dependence on the form of administration and mode of stress].

    PubMed

    Schneider, W; Bussmann, W D; Kober, G; Kaltenbach, M

    1989-01-01

    ISDN (standard release formulation) 40 mg administered 6 times daily (= 240 mg) remained effective during a 4-week treatment of patients with stable angina in terms of decreasing anginal attacks and reducing ischemic ST segment depression at stress testing in the upright position (step climbing test). The sustained antianginal activity is explained by fluctuating plasma levels, provided by rapid drug release from the standard formulation, short administration intervals and an 7-hour-night pause. When comparing acute and chronic antianginal activity of ISDN (40 mg) administered 4 times daily with regard to the type of stress testing it became evident that a marked attenuation of antiischemic activity (-35%; p less than 0.01) occurred in the supine (bicycle ergometry) but not in the upright (step climbing test) position. The most probable explanation for the significant attenuation of efficacy in the supine position is marked blood redistribution into central compartments with increase of cardiac filling pressures during chronic therapy. Rapid development of tolerance both to the hemodynamic and antiischemic effects of glycerol trinitrate within 24 hours could be shown during intravenous administration (3 mg/h) in patients with stable angina. It is concluded that the antiischemic effects of oral ISDN (standard release formulation) administered 4-6 times daily is preserved during long-term therapy due to fluctuating plasma levels. Nitrate therapy providing constant doses over time (e.g. I.V. nitroglycerin) leads to a rapid attenuation of efficacy most probably due to counter regulatory mechanisms. PMID:2531510

  5. 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

    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

  6. Evaluation Case Studies and Intercomparison with Regional Climate Model Simulations based on the DUE PERMAFROST Circumpolar Remote Sensing Service for Permafrost

    NASA Astrophysics Data System (ADS)

    Heim, Birgit; Bartsch, Annett; Elger, Kirsten; Rinke, Annette; Matthes, Heidrun; Zhou, Xu; Klehmet, Katharina; Buchhorn, Marcel; Duguay, Claude

    2014-05-01

    Permafrost is a subsurface phenomenon. However, monitoring from Earth Observation (EO) platforms can provide spatio-temporal data sets on permafrost-related indicators and geophysical parameters used in modelling and monitoring. The ESA Data User Element (DUE) Permafrost project (2009-2012) developed a suite of EO satellite-derived products: Land Surface Temperature (LST), Surface Soil Moisture (SSM), Surface Frozen and Thawed State (Freeze/Thaw), Terrain, Land Cover, and Surface Water. The satellite-derived products are weekly and monthly averages of the bio- and geophysical terrestrial parameters and static circum-Arctic maps. The final DUE Permafrost products cover the years 2007 to 2011 with a circum-Arctic coverage (north of 50°N). The products were released in 2012, and updated in 2013. Further information is available at geo.tuwien.ac.at/permafrost/. The remote sensing service also supports the EU-FP7 funded project PAGE21 - Changing Permafrost in the Arctic and its Global Effects in the 21st Century (www.page21.eu). The Global Terrestrial Network for Permafrost (GTN-P), initiated by the International Permafrost Association (IPA), is the prime program concerned with monitoring of permafrost. It provides an important database for the evaluation of EO-derived products and climate and permafrost models. GTN-P ground data ranges from air-, ground-, and borehole temperature data to active layer monitoring, soil moisture measurements, and the description of landform and vegetation. The involvement of scientific stakeholders and the IPA, and the ongoing evaluation of the satellite-derived products make the DUE Permafrost products relevant to the scientific community. The Helmholtz Climate Initiative REKLIM (Regionale KlimaAnderungen/Regional Climate Change) is a climate research program where regional observations and process studies are coupled with model simulations (http://www.reklim.de/en/home/). ESA DUE Permafrost User workshops initiated the use of EO

  7. ESA Data User Element DUE PERMAFROST Circumpolar Remote Sensing Service for Permafrost - Evaluation Case Studies and Intercomparison with Regional Climate Model Simulations

    NASA Astrophysics Data System (ADS)

    Heim, Birgit; Bartsch, Annett; Elger, Kirsten; Rinke, Annette; Matthes, Heidrun; Zhou, Xu; Klehmet, Katharina; Rockel, Burkhardt; Lantuit, Hugues; Duguay, Claude

    2015-04-01

    Permafrost is a subsurface phenomenon. However, monitoring from Earth Observation (EO) platforms can provide spatio-temporal data sets on permafrost-related indicators and quantities used in modelling and monitoring. The ESA Data User Element (DUE) Permafrost project (2009-2012) developed a suite of EO satellite-derived products: Land Surface Temperature (LST), Surface Soil Moisture (SSM), Surface Frozen and Thawed State (Freeze/Thaw), Terrain, Land Cover, and Surface Water. The satellite-derived products are weekly and monthly averages of the bio- and geophysical terrestrial parameters and static circum-Arctic maps. The final DUE Permafrost products cover the years 2007 to 2011, some products up to 2013, with a circum-Arctic coverage (north of 50°N). The products were released in 2012, and updated in 2013 and 2014. Further information is available at geo.tuwien.ac.at/permafrost/. The remote sensing service also supports the EU-FP7 funded project PAGE21 - Changing Permafrost in the Arctic and its Global Effects in the 21st Century (www.page21.eu). The Global Terrestrial Network for Permafrost (GTN-P), initiated by the International Permafrost Association (IPA), is the prime program concerned with monitoring of permafrost. It provides an important database for the evaluation of EO-derived products and climate and permafrost models. GTN-P ground data ranges from air-, ground-, and borehole temperature data to active layer monitoring, soil moisture measurements, and the description of landform and vegetation. The involvement of scientific stakeholders and the IPA, and the ongoing evaluation of the satellite-derived products make the DUE Permafrost products relevant to the scientific community. The Helmholtz Climate Initiative REKLIM (Regionale KlimaAnderungen/Regional Climate Change) is a climate research program where regional observations and process studies are coupled with model simulations (http://www.reklim.de/en/home/). ESA DUE Permafrost User workshops

  8. 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

  9. 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.

  10. 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.

  11. Using TerraSAR-X and hyperspectral airborne data to monitor surface deformation and physical properties of the Barrow permafrost landscape, Alask

    NASA Astrophysics Data System (ADS)

    Haghshenas-Haghighi, M.; Motagh, M.; Heim, B.; Sachs, T.; Kohnert, K.; Streletskiy, D. A.

    2014-12-01

    In this study, we assess seasonal subsidence/heaving due to thawing/freezing of the permafrost in Barrow (71.3 N, 156.5 W) at the northernmost point of Alaska. The topographic relief in this area is low. Thick Permafrost underlies the entire area, with large ice volumes in its upper layer. With a large collection of field measurements during the past decades at the Barrow Environmental Observatory (BEO), it is an ideal site for permafrost investigation. There are long term systematic geocryological investigations within the Global Terrestrial Network (GTN-P) of the Circumpolar Active Layer Monitoring (CALM) programme. We use 28 TerraSAR-X images, acquired between December 2012 and December 2013 and analyze them using the Small BAseline Subset (SBAS) technique to extract time-series of ground surface deformation. We also analyze hyperspectral images acquired by the airborne AISA sensor over Barrow area, within the AIRMETH2013 programme, to assess physical characteristics such as vegetation biomass and density, surface moisture, and water bodies. Finally, we combine the information derived from both InSAR and hyperspectral analysis, with field measurements to investigate the link between physical characteristics of the permafrost and surface displacement.

  12. Microbial remediation of explosive waste.

    PubMed

    Singh, Baljinder; Kaur, Jagdeep; Singh, Kashmir

    2012-05-01

    Explosives are synthesized globally mainly for military munitions. Nitrate esters, such as GTN and PETN, nitroaromatics like TNP and TNT and nitramines with RDX, HMX and CL20, are the main class of explosives used. Their use has resulted in severe contamination of environment and strategies are now being developed to clean these substances in an economical and eco-friendly manner. The incredible versatility inherited in microbes has rendered these explosives as a part of the biogeochemical cycle. Several microbes catalyze mineralization and/or nonspecific transformation of explosive waste either by aerobic or anaerobic processes. It is likely that ongoing genetic adaptation, with the recruitment of silent sequences into functional catabolic routes and evolution of substrate range by mutations in structural genes, will further enhance the catabolic potential of bacteria toward explosives and ultimately contribute to cleansing the environment of these toxic and recalcitrant chemicals. This review summarizes information on the biodegradation and biotransformation pathways of several important explosives. Isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation are also discussed. This may be useful in developing safer and economic microbiological methods for clean up of soil and water contaminated with such compounds. The necessity of further investigations concerning the microbial metabolism of these substances is also discussed. PMID:22497284

  13. Design study of the geometry of the blanking tool to predict the burr formation of Zircaloy-4 sheet

    SciTech Connect

    Ha, Jisun Lee, Hyungyil Kim, Dongchul Kim, Naksoo

    2013-12-16

    In this work, we investigated factors that influence burr formation for zircaloy-4 sheet used for spacer grids of nuclear fuel roads. Factors we considered are geometric factors of punch. We changed clearance and velocity in order to consider the failure parameters, and we changed shearing angle and corner radius of L-shaped punch in order to consider geometric factors of punch. First, we carried out blanking test with failure parameter of GTN model using L-shaped punch. The tendency of failure parameters and geometric factors that affect burr formation by analyzing sheared edges is investigated. Consequently, geometric factor's influencing on the burr formation is also high as failure parameters. Then, the sheared edges and burr formation with failure parameters and geometric factors is investigated using FE analysis model. As a result of analyzing sheared edges with the variables, we checked geometric factors more affect burr formation than failure parameters. To check the reliability of the FE model, the blanking force and the sheared edges obtained from experiments are compared with the computations considering heat transfer.

  14. Experimental study of heat transfer from shaft in cooled radial bearing of GNT-25 gas turbine

    NASA Astrophysics Data System (ADS)

    Rukhlinskiy, V. V.; Usayev, I. D.; Yermolenko, A. V.

    1984-02-01

    The heat transfer from the shaft in a cooled radial bearing design was studied experimentally in a GTN-25 gas turbine. The basic dimensions of the bearing were 315 mm inside diameter and 140 mm width. This split bearing had two oil feed orifices in the plane of separation and its housing was cooled with oil fed through an annular chamber. Heating of the shaft neck and the bearing housing under operating conditions was simulated. The experimental data have been processed according to methods of similarity and dimensional analysis, the results yielding semiempirical relations for the temperature and the thermal flux at the rubbing surface during laminar and transitional flow. Relations have also been obtained from these data for the hot spot temperature and the friction coefficient at the rubbing surface. The former characterizes the cooling system design and performance, the latter characterizes the bearing efficiency and economy. The results confirm that the effect of energy dissipation in the lubricant on the intensity of heat transfer from the shaft depends largely on the size and the shape of the shaft bearing clearance.

  15. XMM-Newton Education and Public Outreach Program

    NASA Astrophysics Data System (ADS)

    Plait, P.; Silva, S.; Graves, T.; Simonnet, G.; Spear, S.; Slater, G.; Borders, T.; Cominsky, L.

    2003-12-01

    XMM-Newton is a joint NASA-European Space Agency (ESA) orbiting observatory, designed to observe high energy X-rays emitted from exotic astronomical objects such as pulsars, black holes, and active galaxies. It was launched on December 10, 1999 from the ESA base at Kourou, French Guiana and continues to make observations today. In 2003, The NASA E/PO Group at Sonoma State University took the lead for the US portion of the XMM-Newton Education and Public Outreach (E/PO) program. This program is using the mission science to engage students in science and math learning. Currently we are working on developing curriculum materials for grades 6-12. One such product, developed with our new partners at Gettysburg College in Gettysburg, PA, is a Contemporary Laboratory Experiences in Astronomy (CLEA) exercise on X-ray spectroscopy of a supernova remnant. The XMM-Newton E/PO program has also partnered with the GLAST Telescope Network (GTN) and the AAVSO to help coordinate observations of magnetic white dwarfs called polars. This year, the XMM-Newton outreach program will begin the development of a Starlab Planetarium show which will depict the X-ray sky. In addition, the outreach program has created a website (mirrored at NASA's Goddard Space Flight Center) designed to enhance the XMM-Newton mission's science education. More educational materials and information about the XMM-Newton E/PO program can be found at http://xmm.sonoma.edu.

  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. The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease.

    PubMed

    Vasavda, Nisha; Menzel, Stephan; Kondaveeti, Sheila; Maytham, Emma; Awogbade, Moji; Bannister, Sybil; Cunningham, Juliette; Eichholz, Andrew; Daniel, Yvonne; Okpala, Iheanyi; Fulford, Tony; Thein, Swee Lay

    2007-07-01

    Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and alpha globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0.0001 and P < 0.01, respectively). While HMOX1 genotype had no effect, co-inheritance of alpha-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD. PMID:17593033

  18. Physical mapping of human chromosomes by repetitive sequence fingerprinting.

    PubMed Central

    Stallings, R L; Torney, D C; Hildebrand, C E; Longmire, J L; Deaven, L L; Jett, J H; Doggett, N A; Moyzis, R K

    1990-01-01

    We have developed an approach for identifying overlapping cosmid clones by exploiting the high density of repetitive sequences in complex genomes. Individual clones are fingerprinted, using a combination of restriction enzyme digestions followed by hybridization with selected classes of repetitive sequences. This "repeat fingerprinting" technique allows small regions of clone overlap (10-20%) to be unambiguously assigned. We demonstrate the utility of this approach, using the fingerprinting of 3145 cosmid clones (1.25 x coverage), containing one or more (GT)n repeats, from human chromosome 16. A statistical analysis was used to link these clones into 460 contiguous sequences (contigs), averaging 106 kilobases (kb) in length and representing approximately 54% (48.7 Mb) of the euchromatic arms of this chromosome. These values are consistent with theoretical calculations and indicate that 150- to 200-kb contigs can be generated with 1.5 x coverage. This strategy requires the fingerprinting of approximately one-fourth as many cosmids as random strategies requiring 50% minimum overlap for overlap detection. By "nucleating" at specific regions in the human genome, and exploiting the high density of interspersed sequences, this approach allows (i) the rapid generation of large (greater than 100-kb) contigs in the early stages of contig mapping and (ii) the production of a contig map with useful landmarks for rapid integration of the genetic and physical maps. Images PMID:2385591

  19. Noninvasive indicators of atherosclerosis in subclinical hypothyroidism

    PubMed Central

    Kilic, Ismail Dogu; Tanriverdi, Halil; Fenkci, Semin; Akin, Fulya; Uslu, Sukriye; Kaftan, Asuman

    2013-01-01

    Introduction: Cardiovascular system is rich in thyroid hormone receptors and is one of the major sites of action for thyroid hormones. However, the effect of subclinical hypothyroidism (SCH) on atherosclerosis has not been cleared yet. Materials and Methods: SCH is defined as high thyroid-stimulating hormone (TSH) levels in the presence of normal serum T4 and T3 levels. A total of 32 patients with SCH and 29 controls were included in the study. Carotid intima-media thickness, flow-mediated dilatation, and aortic distensibility were compared between the groups. Results: FMD was lower in patients with SCH than in controls. GTN-induced vasodilatation was similar in the patients with SCH and controls. There was no statistically significant difference between the patients with SCH and controls with respect to CIMT and aortic distensibility. Conclusion: SCH is associated with endothelial dysfunction as established by FMD. Inconsistent results of CIMT and aortic stiffness can be explained by these parameters being measures of structural changes whereas FMD is a dynamic measure that reflects the impact of both acute and chronic influences on endothelial function. PMID:23776901

  20. Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease

    PubMed Central

    Bean, Christopher J.; Boulet, Sheree L.; Ellingsen, Dorothy; Pyle, Meredith E.; Barron-Casella, Emily A.; Casella, James F.; Payne, Amanda B.; Driggers, Jennifer; Trau, Heidi A.; Yang, Genyan; Jones, Kimberly; Ofori-Acquah, Solomon F.; Hooper, W. Craig

    2012-01-01

    Sickle cell disease is a common hemolytic disorder with a broad range of complications, including vaso-occlusive episodes, acute chest syndrome (ACS), pain, and stroke. Heme oxygenase-1 (gene HMOX1; protein HO-1) is the inducible, rate-limiting enzyme in the catabolism of heme and might attenuate the severity of outcomes from vaso-occlusive and hemolytic crises. A (GT)n dinucleotide repeat located in the promoter region of the HMOX1 gene is highly polymorphic, with long repeat lengths linked to decreased activity and inducibility. We examined this polymorphism to test the hypothesis that short alleles are associated with a decreased risk of adverse outcomes (hospitalization for pain or ACS) among a cohort of 942 children with sickle cell disease. Allele lengths varied from 13 to 45 repeats and showed a trimodal distribution. Compared with children with longer allele lengths, children with 2 shorter alleles (4%; ≤ 25 repeats) had lower rates of hospitalization for ACS (incidence rate ratio 0.28, 95% confidence interval, 0.10-0.81), after adjusting for sex, age, asthma, percentage of fetal hemoglobin, and α-globin gene deletion. No relationship was identified between allele lengths and pain rate. We provide evidence that genetic variation in HMOX1 is associated with decreased rates of hospitalization for ACS, but not pain. This study is registered at www.clinicaltrials.gov as #NCT00072761. PMID:22966170

  1. 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. PMID:24857499

  2. Analysis of ITS1 sequences and genetic relationships between populations of ridgetail white prawn, Exopalaemon carinicauda, in the East China Sea.

    PubMed

    Zhang, X Z; Cheng, X Q; Yu, Y X; Shen, H; Wan, X H

    2015-01-01

    Internal transcribed spacer 1 (ITS1) sequences from wild-type Exopalaemon carinicauda (N = 124) from the East China Sea were amplified and sequenced. Sequences were polymorphic and ranged from 388 to 583 bp in length. The average content of GC in sequences was significantly higher than that of AT. Altogether, 604 mutant sites with 123 haplotypes were detected; 46.7% were polymorphic sites. The genetic diversity index of population Y was highest, and the lowest was population X. Eight microsatellite sequences were detected; the most-repeated sequences were (GA)n, (AG)n, (GT)n, (TG)n, (TC)n, and (CT)n. Analysis of molecular variance revealed that genetic differentiation among the four populations were very weak, or modest. A molecular evolutionary tree was constructed using the neighbor-joining method and MEGA 6.0, and the phyletic evolutionary relationships among several Palaemonidae species examined. The phylogenetic tree showed that individuals of the same species, as well as the species of the same genus, clustered together, consistent with morphological classifications. PMID:26505380

  3. Borrelia burgdorferi EbfC defines a newly-identified, widespread family of bacterial DNA-binding proteins

    PubMed Central

    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

    2009-01-01

    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 α-helical ‘tweezer’-like structure. PMID:19208644

  4. SOLS: A lake database to monitor in the Near Real Time water level and storage variations from remote sensing data

    NASA Astrophysics Data System (ADS)

    Crétaux, J.-F.; Jelinski, W.; Calmant, S.; Kouraev, A.; Vuglinski, V.; Bergé-Nguyen, M.; Gennero, M.-C.; Nino, F.; Abarca Del Rio, R.; Cazenave, A.; Maisongrande, P.

    2011-05-01

    An accurate and continuous monitoring of lakes and inland seas is available since 1993 thanks to the satellite altimetry missions (Topex-Poseidon, GFO, ERS-2, Jason-1, Jason-2 and Envisat). Global data processing of these satellites provides temporal and spatial time series of lakes surface height with a decimetre precision on the whole Earth. The response of water level to regional hydrology is particularly marked for lakes and inland seas in semi-arid regions. A lake data centre is under development at by LEGOS (Laboratoire d'Etude en Géophysique et Océanographie Spatiale) in Toulouse, in coordination with the HYDROLARE project (Headed by SHI: State Hydrological Institute of the Russian Academy of Science). It already provides level variations for about 150 lakes and reservoirs, freely available on the web site (HYDROWEB: http://www.LEGOS.obs-mip.fr/soa/hydrologie/HYDROWEB), and surface-volume variations of about 50 big lakes are also calculated through a combination of various satellite images (Modis, Asar, Landsat, Cbers) and radar altimetry. The final objective is to achieve in 2011 a fully operating data centre based on remote sensing technique and controlled by the in situ infrastructure for the Global Terrestrial Network for Lakes (GTN-L) under the supervision of WMO (World Meteorological Organization) and GCOS (Global Climate Observing System).

  5. 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. PMID:26057946

  6. Formulation Changes Affect Material Properties and Cell Behavior in HA-Based Hydrogels

    PubMed Central

    Lawyer, Thomas; McIntosh, Kristen; Clavijo, Cristian; Potekhina, Lydia; Mann, Brenda K.

    2012-01-01

    To develop and optimize new scaffold materials for tissue engineering applications, it is important to understand how changes to the scaffold affect the cells that will interact with that scaffold. In this study, we used a hyaluronic acid- (HA-) based hydrogel as a synthetic extracellular matrix, containing modified HA (CMHA-S), modified gelatin (Gtn-S), and a crosslinker (PEGda). By varying the concentrations of these components, we were able to change the gelation time, enzymatic degradation, and compressive modulus of the hydrogel. These changes also affected fibroblast spreading within the hydrogels and differentially affected the proliferation and metabolic activity of fibroblasts and mesenchymal stem cells (MSCs). In particular, PEGda concentration had the greatest influence on gelation time, compressive modulus, and cell spreading. MSCs appeared to require a longer period of adjustment to the new microenvironment of the hydrogels than fibroblasts. Fibroblasts were able to proliferate in all formulations over the course of two weeks, but MSCs did not. Metabolic activity changed for each cell type during the two weeks depending on the formulation. These results highlight the importance of determining the effect of matrix composition changes on a particular cell type of interest in order to optimize the formulation for a given application. PMID:23251160

  7. 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.

  8. Archaea mediate anaerobic oxidation of methane in deep euxinic waters of the Black Sea

    NASA Astrophysics Data System (ADS)

    Wakeham, Stuart G.; Lewis, Cynthia M.; Hopmans, Ellen C.; Schouten, Stefan; Sinninghe Damsté, Jaap S.

    2003-04-01

    We evaluate anaerobic oxidation of methane (AOM) in the Black Sea water column by determining distributions of archaea-specific glyceryl dialkyl glyceryl tetraethers (GDGTs) and 13C isotopic compositions of their constituent biphytanes in suspended particulate matter (SPM), sinking particulate matter collected in sediment traps, and surface sediments. We also determined isotopic compositions of fatty acids specific to sulfate-reducing bacteria to test for biomarker and isotopic evidence of a syntrophic relationship between archaea and sulfate-reducing bacteria in carrying out AOM. Bicyclic and tricyclic GDGTs and their constituent 13C-depleted monocyclic and bicyclic biphytanes (down to -67‰) indicative of archaea involved in AOM were present in SPM in the anoxic zone below 700 m depth. In contrast, GDGT-0 and crenarchaeol derived from planktonic crenarchaeota dominated the GDGT distributions in the oxic surface and shallow anoxic waters. Fatty acids indicative of sulfate-reducing bacteria (i.e., iso- and anteiso-C 15) were not strongly isotopically depleted (e.g., -32 to -25‰), although anteiso-C 15 was 5‰ more depleted in 13C than iso-C 15. Our results suggest that either AOM is carried out by archaea independent of sulfate-reducing bacteria or those sulfate-reducing bacteria involved in a syntrophy with methane-oxidizing archaea constitute a small enough fraction of the total sulfate-reducing bacterial community that an isotope depletion in their fatty acids is not readily detected. Sinking particulate material collected in sediment traps and the underlying sediments in the anoxic zone contained the biomarker and isotope signature of upper-water column archaea. AOM-specific GDGTs and 13C-depleted biphytanes characteristic of the SPM in the deep anoxic zone are not incorporated into sinking particles and are not efficiently transported to the sediments. This observation suggests that sediments may not always record AOM in overlying euxinic water columns and

  9. Allergenic components in modified and unmodified rosin. Chemical characterization and studies of allergenic activity.

    PubMed

    Gäfvert, E

    1994-01-01

    Gäfvert, E. 1994. Allergenic components in modified and unmodified rosin. Chemical characterization and studies of allergenic activity. Acta Dermato-Venereologica. Suppl. 184. 36pp. Uppsala. Unmodified rosin (colophony) is a well-known cause of contact allergy (delayed type hypersensitivity). Rosin is obtained from coniferous trees and consists mainly of diterpenoid resin acids. Most rosin used in technical products is chemically modified. In the common modification of rosin with maleic anhydride, the major product formed is maleopimaric acid (MPA). MPA was identified in experimental sensitization studies as a potent contact allergen. MPA is also formed when rosin is modified with fumaric acid at high temperature and with prolonged heating. The amounts of MPA in technical quality rosins modified with maleic anhydride or fumaric acid might be enough to sensitize individuals handling these rosins. The major product of the modification of rosin with fumaric acid, fumaropimaric acid (FPA), did not elicit any reactions in the animals tested. In another common rosin modification, glycerol esterification, the major product formed was identified as glyceryl triabietate (GTA). In an experimental sensitization study none of the animals reacted to GTA. However, a minor product formed, glyceryl 1-monoabietate (GMA) showed sensitizing capacity. The presence of new contact allergens due to the modification, together with remaining unmodified material, contributes to the risk of developing allergy from contact with these types of rosin. A new main contact allergen in unmodified rosin was identified; 13,14(beta)-epoxyabietic acid. The allergenicity of this epoxide was comparable to that of an earlier identified rosin allergen, 15-hydroperoxyabietic acid (15-HPA). The allergens were detected as their methyl esters. Experimental sensitization and cross-reactivity of oxidation products of resin acids were studied. A pattern of cross-reactivity was observed which indicates that the

  10. RDX Binds to the GABAA Receptor–Convulsant Site and Blocks GABAA Receptor–Mediated Currents in the Amygdala: A Mechanism for RDX-Induced Seizures

    PubMed Central

    Williams, Larry R.; Aroniadou-Anderjaska, Vassiliki; Qashu, Felicia; Finne, Huckelberry; Pidoplichko, Volodymyr; Bannon, Desmond I.; Braga, Maria F. M.

    2011-01-01

    Background Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high-energy, trinitrated cyclic compound that has been used worldwide since World War II as an explosive in both military and civilian applications. RDX can be released in the environment by way of waste streams generated during the manufacture, use, and disposal of RDX-containing munitions and can leach into groundwater from unexploded munitions found on training ranges. For > 60 years, it has been known that exposure to high doses of RDX causes generalized seizures, but the mechanism has remained unknown. Objective We investigated the mechanism by which RDX induces seizures. Methods and results By screening the affinity of RDX for a number of neurotransmitter receptors, we found that RDX binds exclusively to the picrotoxin convulsant site of the γ-aminobutyric acid type A (GABAA) ionophore. Whole-cell in vitro recordings in the rat basolateral amygdala (BLA) showed that RDX reduces the frequency and amplitude of spontaneous GABAA receptor–mediated inhibitory postsynaptic currents and the amplitude of GABA-evoked postsynaptic currents. In extracellular field recordings from the BLA, RDX induced prolonged, seizure-like neuronal discharges. Conclusions These results suggest that binding to the GABAA receptor convulsant site is the primary mechanism of seizure induction by RDX and that reduction of GABAergic inhibitory transmission in the amygdala is involved in the generation of RDX-induced seizures. Knowledge of the molecular site and the mechanism of RDX action with respect to seizure induction can guide therapeutic strategies, allow more accurate development of safe thresholds for exposures, and help prevent the development of new explosives or other munitions that could pose similar health risks. PMID:21362589

  11. Pentaerythritol tetranitrate (PETN) profiling in post-explosion residues to constitute evidence of crime-scene presence.

    PubMed

    Brust, Hanneke; van Asten, Arian; Koeberg, Mattijs; van der Heijden, Antoine; Kuijpers, Chris-Jan; Schoenmakers, Peter

    2013-07-10

    Pentaerythritol tetranitrate (PETN) and its degradation products are analyzed to discriminate between residues originating from PETN explosions and residues obtained under other circumstances, such as natural degradation on textile, or after handling intact PETN. The degradation products observed in post-explosion samples were identified using liquid chromatography-mass spectrometry as the less-nitrated analogues of PETN: pentaerythritol trinitrate (PETriN), pentaerythritol dinitrate (PEDiN) and pentaerythritol mononitrate (PEMN). Significant levels of these degradation products were observed in post-explosion samples, whereas only very low levels were detected in a variety of intact PETN samples and naturally degraded PETN. No significant degradation was observed after 12 weeks of storage at room temperature and the influence of high relative humidity (90%) was found to be small. Natural degradation was accelerated by storage of small amounts of PETN on different types of textile, resembling the clothing of a suspect, at elevated temperature (333K). This resulted in significant levels of PETN degradation products, but the relative amounts remained much lower than in post-explosion PETN. For PETriN the peak area relative to PETN was 0.014 (SD=0.0051) and 0.39 (SD=0.19) respectively. Based on the peak areas of PETriN, PEDiN and PEMN relative to PETN, it was possible to fully distinguish the post-explosion profiles from the profiles obtained from intact PETN or after (accelerated) natural degradation. Although more data are required to accurately assess the strength of the evidence, this work illustrates that PETN profiling may yield valuable evidence when investigating a possible link between a suspect and post-explosion PETN found on a crime scene. Due to the substantial variation in the degradation pattern between explosion experiments and even between sampling positions in one experiment, the method is not able to distinguish different PETN explosion events. PMID

  12. Inhibition of the release of endothelium-derived relaxing factor in vitro and in vivo by dipeptides containing NG-nitro-L-arginine.

    PubMed Central

    Thiemermann, C.; Mustafa, M.; Mester, P. A.; Mitchell, J. A.; Hecker, M.; Vane, J. R.

    1991-01-01

    1. We have shown that dipeptides containing NG-nitro-L-arginine (NO2Arg) inhibit the biosynthesis of endothelium-derived relaxing factor (EDRF) in vitro and in vivo. 2. In anaesthetized rats, intravenous administration at 1-30 mg kg-1 of the methyl ester of NO2Arg, NO2-Arg-L-phenylalanine (NO2Arg-Phe), L-alanyl-NO2Arg (Ala-NO2Arg) or NO2Arg-L-arginine (NO2Arg-Arg) produced dose-related increases in mean arterial blood pressure (MABP) which were unaffected by D-arginine (D-Arg; 20 mg kg-1 min-1 for 15 min), but prevented by co-infusions of L-arginine (L-Arg; 20 mg kg-1 min-1 for 15 min) or by their parent dipeptides. 3. NO2Arg methyl ester, NO2Arg-Phe methyl ester or Ala-NO2Arg methyl ester (10 mg kg-1, i.v.) also inhibited the reduction in MABP caused by the endothelium-dependent vasodilator, acetylcholine (30 micrograms kg-1 min-1 for 3 min), but not those induced by glycerly trinitrate (20 micrograms kg-1 min-1 for 3 min) or iloprost (6 micrograms kg-1 min-1 for 3 min) which act directly on the vascular smooth muscle. 4. Moreover, NO2Arg methyl ester, NO2Arg-Phe methyl ester or NO2Arg-Arg methyl ester (100 microM) inhibited the acetylcholine-induced relaxation of rabbit aortic strips, and NO2Arg-Phe methyl ester (30 microM) blocked the stimulated (bradykinin, 30 pmol) release of EDRF from bovine aortic endothelial cells grown on microcarrier beads.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1786515

  13. 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.

  14. Dissociation Enthalpies of Chloride Adducts of Nitrate and Nitrite Explosives Determined by Ion Mobility Spectrometry.

    PubMed

    Rajapakse, Maneeshin Y; Fowler, Peter E; Eiceman, Gary A; Stone, John A

    2016-02-11

    The kinetics for thermal dissociations of the chloride adducts of the nitrate explosives 1,3-dinitroglycerin (1,3-NG), 1,2-dinitroglycerin (1,2-NG), the nitrite explosive 3,4-dinitrotoluene (3,4-DNT), and the explosive taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB) have been studied by atmospheric pressure ion mobility spectrometry. Both 1,3-NG·Cl(-) and1,2-NG·Cl(-) decompose in a gas-phase SN2 reaction in which Cl(-) displaces NO3(-) while 3,4-DNT·Cl(-) and DMNB·Cl(-) decompose by loss of Cl(-). The determined activation energy (kJ mol(-1)) and pre-exponential factor (s(-1)) values for the dissociations respectively are 1,3-NG·Cl(-), 86 ± 2 and 2.2 × 10(12); 1,2-NG·Cl(-), 97 ± 2 and 3.5 × 10(12); 3,4-DNT·Cl(-), 81 ± 2 and 4.8 × 10(13); and DMNB·Cl(-), 68 ± 2 and 9.7 × 10(11). Calculations by density functional theory show the structures of the nitrate ester adducts involve three hydrogen bonds: one from the hydroxyl group and the other two from the two nitrated carbons. The relative Cl(-) dissociation energies of the nitrates together with the previously reported smaller value for glycerol trinitrate and the calculated highest value for glycerol 1-mononitrate are explicable in terms of the number of hydroxyl hydrogen bond participants. The theoretical enthalpy changes for the nitrate ester displacement reactions are in agreement with those derived from the experimental activation energies but considerably higher for the nitro compounds. PMID:26777731

  15. 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

  16. Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect.

    PubMed

    Niculae, G; Lacatusu, I; Badea, N; Meghea, A

    2012-08-10

    The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions. PMID:22797534

  17. 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. PMID:24954725

  18. 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.

  19. Transdermal baicalin delivery using diethylene glycol monoethyl ether-mediated cubic phase gel.

    PubMed

    Zhang, Yongtai; Zhang, Kai; Guo, Teng; Li, Yuan; Zhu, Chunyun; Feng, Nianping

    2015-02-01

    This study investigated the transdermal permeability of baicalin, a hydrophobic and readily hydrolyzed drug, delivered by glyceryl monooleate (GMO)-based cubic phase gel (CPG) mediated with Transcotol(®) P (TP, diethylene glycol monoethyl ether). A range of CPGs was produced by varying GMO, water, and TP levels. Examination of their physicochemical properties revealed that the optically isotropic CPG showed higher viscosity than lamellar phase gels (LPG), and the baicalin cargo increased CPG viscosity. The GMO:TP ratio and water content also altered viscosity. CPG-mediated delivery increased baicalin's skin permeation, with 76.65- to 200.24-fold higher (p<0.05) transdermal flux than that of a Carbopol(®)-based hydrogel (HDG), and 6.72- to 17.55-fold (p<0.05) higher than that of LPG, with the same water content. Rat in vivo microdialysis showed that CPG produced sustained baicalin release, with superior pharmacokinetic parameters to those of HDG. Furthermore, cutaneous drug absorption was more efficient on rat abdominal skin, compared to that in the chest or scapular region. Effective fusion between the CPG lipid matrix and the stratum corneum may explain this enhancement of transdermal permeation. CPG containing TP therefore, achieved excellent transdermal drug delivery and good baicalin stability, indicating that this system represents a promising transdermal delivery vehicle. PMID:25543112

  20. 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. PMID:25176029

  1. 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. PMID:24421641

  2. Intraoral film containing insulin-phospholipid microemulsion: formulation and in vivo hypoglycemic activity study.

    PubMed

    Rachmawati, Heni; Haryadi, Bernard Manuel; Anggadiredja, Kusnandar; Suendo, Veinardi

    2015-06-01

    Non-invasive administration of insulin is expected for better diabetes mellitus therapy. In this report, we developed intraoral preparation for insulin. Insulin was encapsulated into nanocarrier using self-assembly emulsification process. To increase lipophilicity of insulin, it was dispersed in phospholipid resulted in insulin-phospholipid solid dispersion. The microemulsion formula was established from our previous work which contained glyceryl monooleate (GMO), Tween 20, and polyethylene glycol (PEG 400) in a ratio of 1:8:1. To confirm the formation of insulin-phospholipid solid dispersion, PXRD, FTIR spectroscopy, and Raman spectroscopy were performed. Then, the microemulsion was evaluated for droplet size and distribution, zeta potential, entrapment efficiency, physical stability, and Raman spectroscopy. In addition, microemulsion with expected characteristic was evaluated for in vitro release, in vitro permeation, and in vivo activity. The droplets size of ∼100 nm with narrow distribution and positive charge of +0.56 mV were formed. The insulin encapsulated in the oil droplet was accounted of >90%. Water-soluble chitosan seems to be a promising film matrix polymer which also functioned as insulin release controller. Oral administration of insulin microemulsion to healthy Swiss-Webster mice showed hypoglycemic effect indicating the success of this protein against a harsh environment of the gastrointestinal tract. This effectiveness significantly increased by fourfold as compared to free insulin. Taken together, microemulsion seems to be a promising carrier for oral delivery of insulin. PMID:25511810

  3. Magnetocubosomes for the delivery and controlled release of therapeutics.

    PubMed

    Montis, Costanza; Castroflorio, Benedetta; Mendozza, Marco; Salvatore, Annalisa; Berti, Debora; Baglioni, Piero

    2015-07-01

    The design of nanostructured drug delivery systems (DDS) that improve the efficacy of therapeutic principles by enhancing their biocompatibility, bioavailability and targeting, has been the focus of extensive research over the past years. Of particular relevance in this field is the development of multifunctional architectures that can deliver different therapeutics or diagnostic agents and release them in a controlled way. In this study we report on the design, preparation and characterization of a DDS where hydrophobic Fe3O4 magnetic nanoparticles (NPs) are included in the bilayer of bicontinuous cubic lipid nanoparticles of Glyceryl Monooleate (GMO). The "magnetocubosomes" are characterized and investigated in terms of their ability to encapsulate and release both hydrophilic and hydrophobic model drugs. For the first time Fluorescence Correlation Spectroscopy (FCS) is used to study the diffusion of encapsulated molecules inside the bicontinuous cubic phase and to monitor their release from the matrix towards the aqueous phase. In addition, we show with the same technique that magnetocubosomes are responsive to a low frequency alternating magnetic field (LF-AMF), which acts as an external trigger to boost the release of model drugs confined in the cubic phase. Magnetocubosomes, reported for the first time in this paper, represent a novel biocompatible, multifunctional and responsive DDS. PMID:25533536

  4. Differences in the rheological properties and mixing compatibility with heparinoid cream of brand name and generic steroidal ointments: The effects of their surfactants.

    PubMed

    Kitagawa, Shuji; Yutani, Reiko; Kodani, Rhu-Ichi; Teraoka, Reiko

    2016-01-01

    Most steroidal ointments contain propylene glycol (PG) and surfactants, which improve the solubility of corticosteroids in white petrolatum. Surfactants aid the uniform dispersal of PG within white petrolatum. Since the surfactants used in generic ointments are usually different from those used in brand name ointments, we investigated the effects of surfactants on the rheological properties of three brand name ointments and six equivalent generic ointments. We detected marked differences in hardness, adhesiveness, and spreadability among the ointments. Further examinations of model ointments consisting of white petrolatum, PG, and surfactants revealed that the abovementioned properties, especially hardness and adhesiveness, were markedly affected by the surfactants. Since steroidal ointments are often admixed with moisturizing creams prior to use, we investigated the mixing compatibility of the ointments with heparinoid cream and how this was affected by their surfactants. We found that the ointments containing glyceryl monostearate demonstrated good mixing compatibility, whereas those containing non-ionic surfactants with polyoxyethylene chains exhibited phase separation. These results were also consistent with the findings for the model ointments, which indicates that the mixing compatibility of steroidal ointments with heparinoid cream is determined by the emulsifying capacity of the surfactants in their oily bases. PMID:26958460

  5. 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

  6. 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

    2012-11-01

    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. PMID:23135469

  7. 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.

  8. 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

  9. Organic composition of aerosol particulate matter during a haze episode in Kuala Lumpur, Malaysia

    NASA Astrophysics Data System (ADS)

    Radzi Bin Abas, M.; Rahman, Noorsaadah A.; Omar, Nasr Yousef M. J.; Maah, M. Jamil; Abu Samah, Azizan; Oros, Daniel R.; Otto, Angelika; Simoneit, Bernd R. T.

    The solvent-extractable compounds of urban airborne particulate matter were analyzed to determine the distributions of homologous and biomarker tracers. Samples were collected by high-volume air filtration during the haze episode of 1997 around the University of Malaya campus near Petaling Jaya, a suburb of Kuala Lumpur, Malaysia. These results show that the samples contain n-alkanes, n-alkan-2-ones, n-alkanols, methyl n-alkanoates, n-alkyl nitriles, n-alkanals, n-alkanoic acids, levoglucosan, PAHs, and UCM as the dominant components, with minor amounts of terpenoids, glyceryl esters and sterols, all derived from natural biogenic sources (vascular plant wax), from burning of biomass, and from anthropogenic utilization of fossil fuel products (lubricating oil, vehicle emissions, etc.). Some compositional differences are observed in the samples and greater atmospheric concentrations were found for almost all organic components in the samples collected near a roadway. The results interpreted in terms of major sources are due to local build-up of organic contaminants from vehicular emissions, smoke from biomass burning, and natural background as a result of the atmospheric stability during the haze episodes. The organic components transported in from areas outside the region, assuming all smoke components are external to the city, amount to about 30% of the total organic particle burden.

  10. 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. PMID:19671037

  11. 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. PMID:17407809

  12. Selective solid-phase extraction of alpha-tocopherol by functionalized ionic liquid-modified mesoporous SBA-15 adsorbent.

    PubMed

    Li, Min; Pham, Patrisha J; Pittman, Charles U; Li, Tingyu

    2008-10-01

    Ordered mesoporous adsorbents were prepared by physically grafting functionalized ionic liquids onto SBA-15 (a mesoporous siliceous substrate) using incipient wetness immersion method. These adsorbents were successfully applied to the selective extraction and separation of alpha-tocopherol (an isomer of vitamin E) from a model mixture of soybean oil deodorizer distillate. Various parameters affecting adsorption process such as adsorption time, the structures and loadings of ionic liquids, the adsorption isotherm, and the reusability of adsorbent were investigated using liquid-solid extraction. As high as 211 mg/g adsorbent of the adsorption capacity for alpha-tocopherol was obtained through the adsorption isotherm tests using [emim][Gly]/SBA-15 (functionalized ionic liquid 1-ethyl-3-methylimidazolium glycine which was physically coated on SBA-15) as the adsorbent, in which the functionalized ionic liquids contained the amino acid glycine as the anion. The adsorbent [emim][Gly]/SBA-15 also exhibited a very high adsorption selectivity for alpha-tocopherol. The extraction selectivity or the ratio of distribution coefficients between alpha-tocopherol and the major interference component glyceryl triundecanoate (K(d(alpha-tocopherol))/K(d(triglyceride))) was 10.5. The concentration of alpha-tocopherol was significantly increased from 15.6% in original feedstock solution that contained fatty acid methyl ester, triglyceride and alpha-tocopherol to 73.0% after stripping by diethyl ether. Five adsorbent recycle tests showed good reusability of the functionalized ionic liquid-modified mesoporous adsorbent. PMID:18845881

  13. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate.

    PubMed

    Li, Jing; Wu, Lin; Wu, Weijun; Wang, Baoyan; Wang, Zhongyuan; Xin, Hongliang; Xu, Qunwei

    2013-10-15

    Poor corneal penetration and short preocular retention of a clinical hydrophilic drug, pilocarpine nitrate (PN), for the treatment of open-angle glaucoma and acute angle-closure glaucoma, limit its ocular application. The purpose of this study was to investigate the potential of liquid crystal nanoparticles (LCNPs) for ocular delivery of PN. LCNPs were developed by a top-down method using glyceryl monoolein (GMO) and water in the presence of stabilizer Poloxamer 407. They were characterized by transmission electron microscopy (TEM) and small angle X-ray diffraction (SAXS). The size of LCNP is 202.28±19.32 nm and the encapsulation efficiency reached 61.03%. The in vitro release profiles indicated that PN could keep sustained release from PN-loaded LCNPs for 8h. An ex vivo corneal permeation study revealed that the apparent permeability coefficient of PN-loaded LCNPs was 2.05-fold higher than that of commercial eye drops. In addition, the topical administration test showed that PN-loaded LCNPs had a prolonged effect on decreasing intraocular pressure (IOP) of rabbits compared with commercial drug and physiological saline. In conclusion, LCNPs had been demonstrated to be potential for controlled-release ocular drug delivery. PMID:23916822

  14. 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

    2015-08-01

    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 (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. PMID:26166447

  15. 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. PMID:1613647

  16. 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.

  17. Preparation of a bifunctional pyrazosulfuron-ethyl imprinted polymer with hydrophilic external layers by reversible addition-fragmentation chain transfer polymerization and its application in the sulfonylurea residue analysis.

    PubMed

    Yang, Meixian; Zhang, Yingying; Lin, Shen; Yang, Xinlin; Fan, Zhijin; Yang, Lixia; Dong, Xiangchao

    2013-09-30

    A new bifunctional pyrazosulfuron-ethyl imprinted polymer was synthesized by the combination of molecular imprinting technology and living radical polymerization. In the synthesis, the pyrazosulfuron-ethyl imprinted polymer was obtained by the reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization followed by grafting poly(glyceryl monomethacrylate) (pGMMA) by the post-RAFT polymerization. In this research, we used polyethylene glycol (PEG) as the polymeric porogen in order to increase the porosity of the material which is a new porogen application in the precipitation polymerization. The imprinted polymer has selectivity for the template and ability of humic acids exclusion which has shown the merits of molecularly imprinted polymers and restricted access materials. An online solid-phase extraction/HPLC method for the analysis of three sulfonylurea residues in soil samples has been developed and validated. The recovery of 81-99% in the spiked levels of 40-200 μg kg(-1) was obtained and the limit of detection (LOD) and limit of quantification (LOQ) were less than 4.8 and 15.9 μg kg(-1) respectively. The results demonstrated that this bifunctional material can be used for the efficient pyrazosulfuron-ethyl extraction in the sulfonylurea residue analysis from environmental samples. PMID:23953454

  18. 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. PMID:22809646

  19. Molecular dynamics approach to water structure of H(II) mesophase of monoolein.

    PubMed

    Kolev, Vesselin; Ivanova, Anela; Madjarova, Galia; Aserin, Abraham; Garti, Nissim

    2012-02-21

    The goal of the present work is to study theoretically the structure of water inside the water cylinder of the inverse hexagonal mesophase (H(II)) 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. PMID:22360250

  20. A novel in situ gel for sustained drug delivery and targeting.

    PubMed

    Ganguly, Sudipta; Dash, Alekha K

    2004-05-19

    The objective of this study was to develop a novel chitosan-glyceryl monooleate (GMO) in situ gel system for sustained drug delivery and targeting. The delivery system consisted of 3% (w/v) chitosan and 3% (w/v) GMO in 0.33M citric acid. In situ gel was formed at a biological pH. In vitro release studies were conducted in Sorensen's phosphate buffer (pH 7.4) and drugs were analyzed either by HPLC or spectrophotometry. Characterization of the gel included the effect of cross-linker, determination of diffusion coefficient and water uptake by thermogravimetric analysis (TGA). Mucoadhesive property of the gel was evaluated in vitro using an EZ-Tester. Incorporation of a cross-linker (glutaraldehyde) retarded the rate and extent of drug release. The in vitro release can further be sustained by replacing the free drug with drug-encapsulated microspheres. Drug release from the gel followed a matrix diffusion controlled mechanism. Inclusion of GMO enhanced the mucoadhesive property of chitosan by three- to sevenfold. This novel in situ gel system can be useful in the sustained delivery of drugs via oral as well as parenteral routes. PMID:15113617

  1. 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. PMID:24598140

  2. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25141003

  4. Ethyl oleate-containing nanostructured lipid carriers improve oral bioavailability of trans-ferulic acid ascompared with conventional solid lipid nanoparticles.

    PubMed

    Zhang, Yongtai; Li, Zhe; Zhang, Kai; Yang, Gang; Wang, Zhi; Zhao, Jihui; Hu, Rongfeng; Feng, Nianping

    2016-09-10

    trans-Ferulic acid (TFA) has antioxidative, anti-inflammatory, and cardioprotective effects, but its poor solubility in water results in unsatisfactory oral bioavailability when administered conventionally at a standard dosage. However, the limited bioavailability of TFA can be overcome by delivering it in nanostructured lipid carriers (NLCs). In this study, a microemulsion (ME)-based method was used to prepare NLCs with ethyl oleate as the liquid lipid component and glyceryl behenate as the solid lipid component. These NLCs and solid lipid nanoparticles (SLNs) were then used as vehicles for TFA. Their entrapment efficiencies (EE), stability during storage, in vitro release profiles, and in vivo pharmacokinetics were compared. The NLC formulation afforded a drug entrapment efficiency that was significantly greater than that of the SLN formulation, which was made using a single solid lipid. Furthermore, the TFA that was dispersed in the disordered binary lipid matrix of the NLC formulation was more stable than that in the SLN formulation, and thus showed less expulsion from the vehicle during storage. In in vivo pharmacokinetic studies, the NLC TFA formulation yielded a greater Cmax and AUC than that produced by the SLN formulation and an aqueous TFA suspension. This showed that the oral bioavailability of TFA was markedly improved by packaging in NLCs. NLCs are thus a promising vehicle for oral TFA administration, with significant advantages over SLNs. PMID:27374194

  5. 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. PMID:24927669

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

    PubMed

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

    2004-08-20

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

  7. Vehicle effects on in vitro release and skin permeation of octylmethoxycinnamate from microemulsions.

    PubMed

    Montenegro, L; Carbone, C; Puglisi, G

    2011-02-28

    The high content of surfactants is one of the major limits to microemulsions (MEs) use in pharmaceutical and cosmetic field. In this work MEs with low surfactant content were prepared by the phase inversion temperature (PIT) method using different oil phases and emulsifiers. The effects of vehicle composition on in vitro release and skin permeation of octylmethoxycinnamte (OMC), one of the most used UVB filter, was evaluated. These MEs showed droplet sizes in the range 32-77nm and a single peak in size distribution. MEs prepared using the most lipophilic lipids (decyl oleate or cetyl stearyl isononanoate) showed the lowest stability. In vitro release and skin permeation profiles were affected by both lipophilicty and structure of the lipid used as internal phase and the formulation that released the lowest amount of OMC provided the lowest active compound skin permeation. It is noteworthy that no OMC release and skin permeation were observed using oleth-20/glyceryl oleate as emulsifiers. Furthermore, a skin permeation enhancement effect was observed depending on the vehicle components. The results of this work suggest that PIT MEs could provide controlled skin drug delivery by choosing proper associations of oil phase lipids and emulsifiers. PMID:21129459

  8. Comparative Study of Soybean Oil and the Mixed Fatty Acids as Acyl Donors for Enzymatic Preparation of Feruloylated Acylglycerols in Ionic Liquids.

    PubMed

    Sun, Shangde; Hu, Bingxue; Qin, Fei; Bi, Yanlan

    2015-08-19

    Feruloylated acylglycerols (FAGs) are the lipophilic derivatives of ferulic acid. In this work, soybean oil (SBO) and the mixed fatty acids (MFA) were selected as fatty acyl donors, and reacted with glyceryl monoferulate (GMF) to prepare FAGs in ionic liquids (ILs). Effect of various reaction parameters (time, temperature, enzyme concentration, and substrate ratio) and ILs on the GMF conversion and the reaction selectivity for FAGs formation were investigated. Response surface methodology (RSM) based on a 3-level-4-factor Box-Behnken experimental design was employed to evaluate the inactive effect of reaction parameters. For the esterification of GMF with MFA, the maximum GMF conversion (98.9 ± 0.9%) and FAG yield (88.9 ± 0.6%) were achieved in [C10mim]PF6. However, for the transesterification of GMF with SBO, the maximum GMF conversion (94.3 ± 0.7%) and FAG yield (83.8 ± 1.0%) were obtained in [C12mim]PF6. High FAG selectivities (∼0.90) were also obtained using SBO or MFA as acyl donors. PMID:26194470

  9. Direct and Highly Selective Drug Optosensing in Real, Undiluted Biological Samples with Quantum-Dot-Labeled Hydrophilic Molecularly Imprinted Polymer Microparticles.

    PubMed

    Yang, Yaqiong; Niu, Hui; Zhang, Huiqi

    2016-06-22

    Quantum-dot (QD)-labeled hydrophilic molecularly imprinted polymer (MIP) microparticles were prepared for direct and highly selective optosensing of an antibiotic drug (i.e., tetracycline (Tc)) in pure bovine/goat milks and bovine/porcine serums. "Living" CdTe QD-SiO2 composite microparticles with alkyl bromide groups on their surfaces were first obtained via the one-pot sol-gel reaction, and they were subsequently grafted with a Tc-imprinted polymer layer and poly(glyceryl monomethacrylate) brushes via the successive surface-initiated atom transfer radical polymerizations. The resulting MIP microparticles with QD labeling and hydrophilic polymer brushes could function properly in biological samples and showed obvious template-binding-induced fluorescence quenching, which make them a useful fluorescent chemosensor with limits of detection down to 0.14 μM in complex biological media. Moreover, a facile and effective approach was developed based on a newly derived equation to eliminate the false positives of the fluorescent chemosensor and provide it with wider linear detection concentration ranges in comparison with those obtained using the generally adopted Stern-Volmer equation. Furthermore, the fluorescent MIP chemosensor was also successfully applied for directly, sensitively, selectively, and accurately quantifying Tc in biological media, and the average recoveries were in the range of 95%∼105% even when several other drugs and the fluorescently interfering chlortetracycline were present in the samples. PMID:27238184

  10. Two Distinct Cylinder Arrangements in Monodomains of a Lyotropic Liquid Crystalline Hexagonal II Phase: Monodomains with Straight Cylinders and Ringed Cylinders in Capillaries.

    PubMed

    Oka, Toshihiko; Ohta, Noboru

    2016-08-01

    We report a method to produce two different monodomains of an inverse hexagonal II (HII) phase in capillaries. Capillaries filled with glyceryl monooleyl ether (GME) in an inverted micellar phase were soaked in water. After a week, a monodomain of the HII phase with straight cylinders was observed in a capillary with a diameter of 1.0 mm. The axis of the straight cylinders was almost parallel to the capillary axis, and the cylinders were slightly undulated. The lattice constant of the HII phase was 5.85 nm, which indicated the monodomain was fully hydrated. Another monodomain with ringed cylinders was observed in a 0.2 mm diameter capillary. The ringed cylinders aligned to the round capillary wall, where one of the ⟨10⟩ directions in the hexagonal lattice always faced the wall. The lattice constant was 4.89 nm, from which the estimated water content of the monodomain was almost the lowest reported for the HII phase. The monodomain with ringed cylinders is stabilized by the capillary wall and the low water content. This method to produce specific monodomains is expected to be of benefit for basic and applied research on the HII phase. PMID:27399256

  11. Abiotic formation of acylglycerols under simulated hydrothermal conditions and self-assembly properties of such lipid products

    NASA Astrophysics Data System (ADS)

    Simoneit, Bernd R. T.; Rushdi, Ahmed I.; Deamer, David W.

    The abiotic formation of aliphatic lipid compounds (i.e., fatty acids, alcohols, and acylglycerols) has been reported to occur at elevated temperatures and pressures under simulated hydrothermal conditions. Although abiotic synthetic chemistry can occur under these conditions, the prebiotic self-assembly of micelles to bilayer to vesicles (protocells) may have occurred elsewhere. Amphiphilic compounds such as fatty acids are important candidates for micelle/bilayer/vesicle formation, because they are abundant products of Fischer-Tropsch-type reactions and are also found in carbonaceous meteorites. Thus, it is of interest to determine whether more complex amphiphilic precursor compounds, capable of assembling into stable membrane structures, can be synthesized under hydrothermal conditions. Hydrothermal experiments were conducted to study condensation reactions of model lipid precursors in aqueous media, i.e., glycerol and alkanoic acids, to form acylglycerols (glyceryl alkanoates) at elevated temperature under confining pressure. Nine different alkanoic acids ranging from C 7 to C 16 (except C 8) were used in these experiments. The condensation products were two isomers each of monoacylglycerols and diacylglycerols, as well as the corresponding triacylglycerol. The results indicated that: (1) condensation (dehydration) reactions are possible under aqueous pyrolysis conditions; (2) abiotic synthesis and subsequent condensation reactions of aliphatic lipid compounds are possible under hydrothermal conditions; and (3) such molecules have robust properties of self-assembly into membranous structures that would be suitable boundary structures for primitive forms of cellular life.

  12. Abiotic synthesis of acylglycerols under simulated hydrothermal conditions and micelle formation

    NASA Astrophysics Data System (ADS)

    Simoneit, B.; Rushdi, A.; Deamer, D.

    Abiotic formation of aliphatic lipid compounds i e fatty acids alcohols and acylglycerols has been reported to occur at elevated temperatures and pressures under simulated hydrothermal conditions McCollom et al 1999 Rushdi and Simoneit 2001 2006 Although abiotic chemistry may occur at these conditions the prebiotic self-assembly of micelles to bilayer to vesicles protocells may have occurred elsewhere Amphipathic compounds such as fatty acids and acylglycerols are important candidates for micelle bilayer vesicle formation Thus it is of interest to demonstrate that abiotic lipids amphiphiles precursor compounds for abiotic cellular membranes Deamer 1997 can be synthesized under hydrothermal conditions Hydrothermal experiments were conducted to study condensation reactions of model lipid precursors in aqueous media to form acylglycerols glyceryl alkanoates at elevated temperatures under confining pressures Stainless steel vessels 316SS Sno-Trik high pressure couplings with internal capacities of 286 underline 2 mu l were used for the condensation reactions using a mixture of 0 14 mM glycerol and 0 35 mM of n-alkanoic acid Nine different alkanoic acids ranging from C 7 to C 16 except C 8 were used in these experiments The condensation products were two isomers each of monoacylglycerols and diacylglycerols as well as the corresponding triacylglycerol The product yields were 13-28 for monoacylglycerols 6-13 for diacylglycerols and 1-4 for triacylglycerols The results indicated that 1

  13. Comparison of lipopeptide-based immunocontraceptive vaccines containing different lipid groups.

    PubMed

    Chua, Brendon Y; Zeng, Weiguang; Lau, Yuk Fai; Jackson, David C

    2007-01-01

    We have previously shown that incorporating the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys) into peptide structures effectively adjuvants otherwise weak immunogens. In this study lipopeptides based on luteinising hormone releasing hormone (LHRH) as a B cell epitope, [B], were synthesised in tandem with a 17-residue T-helper epitope, [T], derived from the fusion protein of the morbillivirus canine distemper virus. In this way vaccine candidates with the structure [T]-[B] were produced. These peptides were then lipidated with different diacylated moieties. The acyl moieties used were: palmitic acid (C16) to give Pam2Cys, stearic acid (C18) to give Ste2Cys, lauric acid (C12) to give Lau2Cys and octanoic acid (C8) to give Oct2Cys. We compared the immunogenicities of these simple lipopeptides in BALB/c mice by measuring their ability to induce anti-LHRH antibodies and found that immunogenicity was dependent on the length of the alkane chains of the incorporated lipid moieties with the hierarchy C16=C18>C12>C8. The antibody levels elicited by the lipopeptides also correlated with their ability to inhibit the reproductive capability of female mice in fertility trials. Furthermore, the C16 lipopeptide was the most effective in activating dendritic cells, measured by up regulation of surface MHC Class II molecules, and also in activating NF-kappaB in a Toll-like receptor-2 (TLR2)-dependent manner. PMID:17055123

  14. Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori.

    PubMed

    Abou Youssef, Nancy Abdel Hamid; Kassem, Abeer Ahmed; El-Massik, Magda Abd Elsamea; Boraie, Nabila Ahmed

    2015-01-01

    The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol(®) and Compritol(®) were incorporated into G-based formulations (G1%C1%). Mz:lipid ratio was 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing. Alg4%C2% FRS exhibited short gelation lag time (3s), long duration (>24h), floating lag time 1m in and duration >24h, and a reliable sustained drug release (MDT 6h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz:GMS 1:1) enhanced the gelation lag time and duration (6s and >24h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori. PMID:25843757

  15. 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. PMID:26292931

  16. Exploring Microstructural Changes in Structural Analogues of Ibuprofen-Hosted In Situ Gelling System and Its Influence on Pharmaceutical Performance.

    PubMed

    Patil, Sharvil S; Venugopal, Edakkal; Bhat, Suresh; Mahadik, Kakasaheb R; Paradkar, Anant R

    2015-10-01

    The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model. PMID:25716330

  17. Isotopic exchange during derivatization of platelet activating factor for gas chromatography-mass spectrometry

    SciTech Connect

    Haroldsen, P.E.; Gaskell, S.J.; Weintraub, S.T.; Pinckard, R.N. )

    1991-04-01

    One approach to the quantitative analysis of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; also referred to as AGEPC, alkyl glyceryl ether phosphocholine) is hydrolytic removal of the phosphocholine group and conversion to an electron-capturing derivative for gas chromatography-negative ion mass spectrometry. (2H3)Acetyl-AGEPC has been commonly employed as an internal standard. When 1-hexadecyl-2-(2H3)acetyl glycerol (obtained by enzymatic hydrolysis of (2H3)-C16:0 AGEPC) is treated with pentafluorobenzoyl chloride at 120 degrees C, the resulting 3-pentafluorobenzoate derivative shows extensive loss of the deuterium label. This exchange is evidently acid-catalyzed since derivatization of 1-hexadecyl-2-acetyl glycerol under the same conditions in the presence of a trace of 2HCl results in the incorporation of up to three deuterium atoms. Isotope exchange can be avoided if the reaction is carried out at low temperature in the presence of base. Direct derivatization of (2H3)-C16:0 AGEPC by treatment with pentafluorobenzoyl chloride or heptafluorobutyric anhydride also results in loss of the deuterium label. The use of (13C2)-C16:0 AGEPC as an internal standard is recommended for rigorous quantitative analysis.

  18. 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.

  19. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder.

    PubMed

    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

  20. Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier.

    PubMed

    Almoussalam, Musallam; Zhu, Huijun

    2016-01-01

    The only formula of dacarbazine (Dac) in clinical use is intravenous infusion, presenting a poor therapeutic profile due to the low dispersity of the drug in aqueous solution. To overcome this, a nanostructured lipid carrier (NLC) consisting of glyceryl palmitostearate and isopropyl myristate was developed to encapsulate Dac. NLCs with controlled size were achieved using high shear dispersion (HSD) following solidification of oil-in-water emulsion. The synthesis parameters, including surfactant concentration, the speed and time of HSD were optimized to achieve the smallest NLC with size, polydispersion index and zeta potential of 155 ± 10 nm, 0.2 ± 0.01, and -43.4 ± 2 mV, respectively. The optimal parameters were also employed for Dac-loaded NLC preparation. The resultant NLC loaded with Dac possessed size, polydispersion index and zeta potential of 190 ± 10 nm, 0.2 ± 0.01, and -43.5 ± 1.2 mV, respectively. The drug encapsulation efficiency and drug loading reached 98% and 14%, respectively. This is the first report on encapsulation of Dac using NLC, implying that NLC could be a new potential candidate as drug carrier to improve the therapeutic profile of Dac. PMID:27168058

  1. 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. PMID:26760943

  2. Bioavailability of starch based hot stage extrusion formulations.

    PubMed

    Henrist, D; Lefebvre, R A; Remon, J P

    1999-10-01

    The aim of the study was to develop a starch based hot stage extrusion formulation for controlled drug delivery and to evaluate its in vivo behavior. The extrusion mixture consisted of 53% corn starch as the matrix forming agent, 15% sorbitol as a plasticizer, 30% theophylline monohydrate as the model drug and 2% glyceryl monostearate as a lubricant. The extrudates were produced by means of a corotating twin screw extruder of APV Baker equipped with a twin screw powder feeder and a 3-mm cylindrical die. During extrusion 20% water (based on the wet mass) was added to the powder mixture. The extrudates were dried in an oven at 60 degrees C during 48 h, cut and filled out in hard gelatine capsules, in a way that the content of two capsules corresponded with a dose of 300 mg anhydrous theophylline. The dissolution profile of the experimental dosage form was retarded with a drug release of around 80% in 8 h. The in vivo behavior of the experimental formulation was evaluated in a randomized crossover design study (n=8) with a commercially available multiple unit sustained release product as the reference formulation. The plasma samples were analyzed by a validated HPLC-UV method with solid phase extraction for the sample preparation. It was clear that the experimental formulation exhibited sustained release behavior, but that it performed less well than the multiple unit dosage form. PMID:10502624

  3. Purification and Characterization of an A Type Phospholipase from Potato and Its Effect on Potato Mitochondria 12

    PubMed Central

    Hasson, Edna P.; Laties, George G.

    1976-01-01

    A potato (Solanum tuberosum) phospholipid acyl-hydrolase, which - in the pH range 7.5 to 8.5—is at least 10,000 times more effective with phospholipids than with galactolipids, has been purified and characterized. It is a soluble enzyme readily distinguished from a neutral lipid lipase and a third lipid acyl-hydrolase which, while acting on phospholipid, shows a decided preference for glyceryl monoolein. The phospholipase in question has a pH optimum of 8.5, is stimulated by Ca2+ at pH above 7.5 and inhibited by Ca2+ at lower pH, is not dependent on detergents although stimulated by Triton X-100 to a moderate extent, and remains very active at temperatures close to zero. The phospholipids of intact potato mitochondria are highly susceptible to degradation by potato phospholipase, and it is suggested that this enzyme is involved in the extensive lipid breakdown which occurs in fresh potato slices following cutting, and in the deterioration of mitochondria during their preparation and aging. PMID:16659439

  4. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study

    PubMed Central

    Shah, Nirmal V.; Seth, Avinash K.; Balaraman, R.; Aundhia, Chintan J.; Maheshwari, Rajesh A.; Parmar, Ghanshyam R.

    2016-01-01

    The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 32 factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and −12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX. PMID:27222747

  5. Stimuli responsive liquid crystals provide 'on-demand' drug delivery in vitro and in vivo.

    PubMed

    Fong, Wye-Khay; Hanley, Tracey; Boyd, Ben J

    2009-05-01

    Lipid-based liquid crystalline materials have been proposed as controlled drug delivery systems. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, however there has been little progress towards the use of in situ changes to nanostructure to control drug release. In this study, phytantriol and glyceryl monooleate-based bicontinuous cubic (Q2) and inverse hexagonal (H2) nanostructures have been designed to allow change to the nanostructure in response to external change in temperature, with a view to controlling drug release rates in vivo. Changes to nanostructure with temperature were confirmed by crossed polarised optical microscopy and small angle X-ray scattering. Phytantriol containing 3% (w/w) vitamin E acetate provided the necessary phase transition behaviour to progress this system to in vitro release and in vivo proof of concept studies. Using glucose as a model hydrophilic drug, drug diffusion was shown to be reversible on switching between the H2 and Q2 nanostructures at temperatures above and below physiological temperature respectively. An in vivo proof of concept study in rats showed that after subcutaneous administration of these materials, the changes in nanostructure induced by application of a heat or cool pack at the injection site stimulated changes in drug release from the matrix anticipated from in vitro release behaviour, thereby demonstrating the potential utility of these systems as 'on demand' drug release delivery vehicles. PMID:19331865

  6. Effect of ionic surfactants on the iridescent color in lamellar liquid crystalline phase of a nonionic surfactant.

    PubMed

    Chen, Xinjiang; Mayama, Hiroyuki; Matsuo, Goh; Torimoto, Tsukasa; Ohtani, Bunsho; Tsujii, Kaoru

    2007-01-15

    A nonionic surfactant, n-dodecyl glyceryl itaconate (DGI), self-assembles into bilayer membranes in water having a spacing distance of sub-micrometer in the presence of small amounts of ionic surfactants, and shows beautiful iridescent color. Ionic surfactants have strong effects on this iridescent system. We have interestingly found that the iridescent color changes with time after mixing DGI and ionic surfactants and the color in equilibrium state changes greatly with concentration of the ionic surfactants. The time-dependent color change results from the transformation of DGI aggregate structure after being mixed with ionic surfactant. It is first found that the iridescent color of this nonionic system can be changed from red to deep blue by altering the concentration of ionic surfactants added even though the total concentration of surfactant is almost constant. Such large blue shift of the iridescent color in equilibrium state cannot be fully explained by the ordinary undulation theory applied so far for this phenomenon. The flat lamellar sheets tend to curve by increasing the concentration of ionic surfactants to form separated onion-like and/or myelin-like structures. These separated structures of lamellar system result in the decrease of spacing distance between bilayer membranes because some vacant spaces necessarily appear among these structures. PMID:17046012

  7. 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

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

    PubMed Central

    Pawar, Harshal Ashok; Joshi, Pooja Rasiklal

    2014-01-01

    Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol) were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation. PMID:26556200

  9. Tricin derivatives as anti-inflammatory and anti-allergic constituents from the aerial part of Zizania latifolia.

    PubMed

    Lee, Seung-Su; Baek, Yoon-Su; Eun, Cheong-Su; Yu, Mi-Hee; Baek, Nam-In; Chung, Dae-Kyun; Bang, Myun-Ho; Yang, Seun-Ah

    2015-01-01

    Methanol extract of Zizania latifolia was partitioned with EtOAc, n-BuOH, and H2O. From the EtOAc layers, a new flavonolignan along with a known flavone and three known flavonolignans, tricin (1), salcolin A (2), salcolin B (3), and salcolin C (4), were isolated through repeated silica gel and ODS column chromatography. The chemical structure of the new flavonolignan was determined to be tricin-4'-O-[erythro-β-guaiacyl-(7″-O-methyl)-glyceryl] ether and was named salcolin D (5) based on physicochemical and spectroscopic data, including FT-NMR and ESI-MS. All compounds were isolated for the first time from this plant. Compounds 2-5, tricin derivatives, all exhibited higher anti-inflammatory and anti-allergy activities than tricin. In particular, salcolin D (5) was shown to have the strongest inhibitory activity against LPS-induced NO production in RAW 264.7 cells as well as β-hexosaminidase release in IgE-sensitized RBL-2H3 cells. These results suggest that the presence of tricin derivatives conveys allergy and inflammation treatment ability to Z. latifolia. PMID:25559019

  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. PMID:23916823

  11. 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. PMID:19720123

  12. 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.

  13. 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.

  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. 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. PMID:26537654

  16. 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.

  17. 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.

  18. Independent regulation of chylomicron lipolysis and particle removal rates: effects of insulin and thyroid hormones on the metabolism of artificial chylomicrons.

    PubMed

    Zerbinatti, C V; Oliveira, H C; Wechesler, S; Quintao, E C

    1991-11-01

    The processes of chylomicron lipolysis and removal from plasma were investigated by the intra-arterial infusion of doubly labeled artificial chylomicrons in rats. The rate of lipolysis was measured as a delipidation index (DI), which is the glyceryl-tri-9,10(N)-3H oleate (3H-TO) fraction removed from the particle as fatty acids, whereas the cholesteryl(1-14C) oleate (14C-CO) plasma disappearance rate measures the splanchnic organ particle uptake. In the alloxan-diabetic rats, despite a normal DI, the 14C-CO plasma residence time (RT) was longer than in control animals and remained longer after stimulation of the lipoprotein lipase by heparin. DI and 14C-CO removal rate were not significantly altered by insulin administration to glucose-supplemented control rats. Lipolysis was remarkable in propylthiouracil (PTU)-induced hypothyroidism, and yet the 14C-CO removal rate was retarded. In hypothyroidism, heparin enhanced the 14C-CO removal more than in the control group; however, after heparin, the 14C-CO RT still remained higher in the hypothyroid animals as compared with the control group. Hyperthyroidism lowered the DI; nevertheless, the 14C-CO disappearance rate was faster than in controls. In summary, lack or excess of thyroid hormone influences both the chylomicron lipolysis and removal systems, whereas lack of insulin impairs mostly the particle removal from plasma, and excess of insulin has no effect on the chylomicron metabolism. PMID:1943739

  19. 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

  20. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS.

    PubMed

    Woo, Jong Soo; Kim, Tae-Seo; Park, Jae-Hyun; Chi, Sang-Cheol

    2007-01-01

    Silymarin has been used to treat hepatobiliary diseases. However, it has a low bioavailability after being administered orally on account of its low solubility in water. In order to improve the dissolution rate, silymarin was formulated in the form of a self-microemulsifying drug delivery system (SMEDDS). The optimum formulation of SMEDDS containing silymarin was obtained based on the study of pseudo-ternary phase diagram. The SMEDDS consisted of 15% silymarin, 10% glyceryl monooleate as the oil phase, a mixture of polysorbate 20 and HCO-50 (1:1) as the surfactant, Transcutol as the cosurfactant with a surfactant/cosurfactant ratio of 1. The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was 67 nm. The % release of silybin from the SMEDDS after 6 hours was 2.5 times higher than that from the reference capsule. After its oral administration to rats, the bioavailability of the drug from the SMEDDS was 3.6 times higher than the reference capsule. PMID:17328246

  1. An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to isoquercitrin.

    PubMed

    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

  2. Application of dynamic mechanical analysis (DMA) to determine the mechanical properties of pellets.

    PubMed

    Bashaiwoldu, Abraham B; Podczeck, F; Newton, J M

    2004-01-28

    Pellets of a wide range of mechanical properties were produced by the process of extrusion and spheronisation using various formulation factors. A range of mechanical properties from a simple fracture load to detailed load/displacement curves obtained when pellets were subjected to diametral compression test and a bed of pellets was compacted, were used to provide measure of tensile strength, deformability, linear strain, elastic modulus, yield and shear strength. Such conventional techniques resulted in irreversible damage to the structure of the pellets and were unable to establish the viscoelastic properties of the pellets. The application of the dynamic mechanical analysis (DMA), however, allowed the determination of (1) an accurate Young's modulus of elasticity, which was found to be between 8.4 and 24-fold higher than that determined from the diametral compression test, (2) the presence of a reversible elastic deformation even after the yield point in terms of storage modulus and (3) a change in the values of the phase angle, which illustrates the increase in viscoelasticity of the pellets formed with ethanol, glyceryl monostearate (GMS) or glycerol, while a decrease in viscoelasticity with the incorporation of lactose into the microcrystalline cellulose (MCC) pellets. This work further demonstrated that the only feasible technique for determining the elastic and plastic deformability of the pellets is the one which subjects the specimen to stress/relaxation cycles and can determine the dissipated energy in terms of loss modulus or phase angle, and that is DMA. PMID:14706245

  3. Effects of hexagonal boron nitride on dry compression mixture of Avicel DG and Starch 1500.

    PubMed

    Uğurlu, Timuçin; Halaçoğlu, Mekin Doğa

    2016-01-01

    The objective of this study was to investigate the lubrication properties of hexagonal boron nitride (HBN) on a (1:1) binary mixture of Avicel DG and Starch 1500 after using the dry granulation-slugging method and compare it with conventional lubricants, such as magnesium stearate (MGST), glyceryl behenate (COMP) and stearic acid (STAC). MGST is one of the most commonly used lubricants in the pharmaceutical industry. However, it has several adverse effects on tablet properties. In our current study, we employed various methods to eradicate the work hardening phenomenon in dry granulation, and used HBN as a new lubricant to overcome the adverse effects of other lubricants on tablet properties. HBN was found to be as effective as MGST and did not show any significant adverse effects on the crushing strength or work hardening. From the scanning electron microscope (SEM) images, it was concluded that HBN distributed better than MGST. As well as showing better distribution, HBN's effect on disintegration was the least pronounced. Semi-quantitative weight percent distribution of B and N elements in the tablets was obtained using EDS (energy dispersive spectroscopy). Based on atomic force microscope (AFM) surface roughness images, formulations prepared with 1% HBN showed better plastic character than those prepared with MGST. PMID:25716058

  4. Mannosylglycerate: structural analysis of biosynthesis and evolutionary history.

    PubMed

    Borges, Nuno; Jorge, Carla D; Gonçalves, Luís G; Gonçalves, Susana; Matias, Pedro M; Santos, Helena

    2014-09-01

    Halophilic and halotolerant microorganisms adapted to thrive in hot environments accumulate compatible solutes that usually have a negative charge either associated with a carboxylic group or a phosphodiester unit. Mannosylglycerate (MG) has been detected in several members of (hyper)thermophilic bacteria and archaea, in which it responds primarily to osmotic stress. The outstanding ability of MG to stabilize protein structure in vitro as well as in vivo has been convincingly demonstrated. These findings led to an increasingly supported link between MG and microbial adaptation to high temperature. However, the accumulation of MG in many red algae has been known for a long time, and the peculiar distribution of MG in such distant lineages was intriguing. Knowledge on the biosynthetic machinery together with the rapid expansion of genome databases allowed for structural and phylogenetic analyses and provided insight into the distribution of MG. The two pathways for MG synthesis have distinct evolutionary histories and physiological roles: in red algae MG is synthesised exclusively via the single-step pathway and most probably is unrelated with stress protection. In contrast, the two-step pathway is strongly associated with osmoadaptation in (hyper)thermophilic prokaryotes. The phylogenetic analysis of the two-step pathway also reveals a second cluster composed of fungi and mesophilic bacteria, but MG has not been demonstrated in members of this cluster; we propose that the synthase is part of a more complex pathway directed at the synthesis of yet unknown molecules containing the mannosyl-glyceryl unit. PMID:25108362

  5. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

    PubMed

    Amenta, F; Tayebati, S K

    2008-01-01

    Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate. PMID:18289004

  6. 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

  7. DNA Before Proteins? Recent Discoveries in Nucleic Acid Catalysis Strengthen the Case

    NASA Astrophysics Data System (ADS)

    Burton, Aaron S.; Lehman, Niles

    2009-02-01

    An RNA-DNA World could arise from an all-RNA system with the development of as few as three ribozymes -- a DNA-dependent RNA polymerase, an RNA-dependent DNA polymerase, and a catalyst for the production of DNA nucleotides. A significant objection to DNA preceding proteins is that RNA has not been shown to catalyze the production of DNA. However, RNA- and DNAzymes have been recently discovered that catalyze chemical reactions capable of forming deoxyribose, such as mixed aldol condensation of 5'-glyceryl- and 3'-glycoaldehyde-terminated DNA strands. Thus, the only remaining obstacles to RNA-catalyzed in vitro DNA synthesis are alterations of substrate and template specificities of known ribozymes. The RNA-DNA World lessens genomic size constraints through a relaxed error threshold, affording the evolutionary time needed to develop protein synthesis. Separation of information from catalyst enables genotype and phenotype to be readily discriminated by absence or presence, respectively, of the 2'-OH. Novel ribozymes that arise through mutation can be preserved in DNA by reverse transcription, which makes them much more likely to be retained than in an RNA-genome milieu. The extra degree of separation between protein and mRNA, in terms of identifying and then retaining a useful enzyme, may have in fact necessitated storing information in DNA prior to the advent of translation.

  8. Formation, antioxidant property and oxidative stability of cold pressed rice bran oil emulsion.

    PubMed

    Thanonkaew, Amonrat; Wongyai, Surapote; Decker, Eric A; McClements, David J

    2015-10-01

    Cold pressed rice bran oil (CPRBO) is used in foods, cosmetics, and pharmaceuticals due to its desirable health and functional attributes. The purpose of this work was to study the formation, antioxidant property and oxidative stability of oil-in-water emulsion of CPRBO. The influence of oil (10-40 % CPRBO) and surfactant (1-5 % glyceryl monostearate (GMS)) concentration on the properties of emulsions were studied. The lightness (L*) and yellowness (b*) of CPRBO emulsions decreased as GMS concentration increased, which was attributed to a decrease in droplet size after homogenization. The CPRBO emulsion was stable during storage at room temperature for 30 days. Increasing the oil concentration in the CPRBO emulsions increased their antioxidant activity, which can be attributed to the corresponding increase in phytochemical content. However, GMS concentration had little impact on the antioxidant activity of CPRBO emulsions. The storage of CPRBO emulsion at room temperature showed that lipid oxidation markers gradually increased after 30 days of storage, which was correlated to a decrease in gamma oryzanol content and antioxidant activity. These results have important implications for the utilization of rice bran oil (RBO) as a function ingredient in food, cosmetic, and pharmaceutical products. PMID:26396397

  9. 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. PMID:20364857

  10. 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. PMID:25203610

  11. Preparation of reusable bioreactors using reversible immobilization of enzyme on monolithic porous polymer support with attached gold nanoparticles.

    PubMed

    Lv, Yongqin; Lin, Zhixing; Tan, Tianwei; Svec, Frantisek

    2014-01-01

    Porcine lipase has been reversibly immobilized on a monolithic polymer support containing thiol functionalities prepared within confines of a fused silica capillary and functionalized with gold nanoparticles. Use of gold nanoparticles enabled rejuvenation of the activity of the deactivated reactor simply by stripping the inactive enzyme from the nanoparticles using 2-mercaptoethanol and subsequent immobilization of fresh lipase. This flow through enzymatic reactor was then used to catalyze the hydrolysis of glyceryl tributyrate (tributyrin). The highest activity was found within a temperature range of 37-40°C. The reaction kinetics is characterized by Michaelis-Menten constant, Km  = 10.9 mmol/L, and maximum reaction rate, Vmax  = 5.0 mmol/L min. The maximum reaction rate for the immobilized enzyme is 1,000 times faster compared to lipase in solution. The fast reaction rate enabled to achieve 86.7% conversion of tributyrin in mere 2.5 min and an almost complete conversion in 10 min. The reactor lost only less than 10% of its activity even after continuous pumping through it a solution of substrate equaling 1,760 reactor volumes. Finally, potential application of this enzymatic reactor was demonstrated with the transesterification of triacylglycerides from kitchen oil to fatty acid methyl esters thus demonstrating the ability of the reactor to produce biodiesel. PMID:23860941

  12. Development of New Lipid-Based Paclitaxel Nanoparticles Using Sequential Simplex Optimization

    PubMed Central

    Dong, Xiaowei; Mattingly, Cynthia A.; Tseng, Michael; Cho, Moo; Adams, Val R.; Mumper, Russell J.

    2008-01-01

    The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes. PMID:19111929

  13. 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).

  14. Neutral polar methacrylate-based monoliths for normal phase nano-LC and CEC of polar species including N-glycans.

    PubMed

    Zhong, Hengwen; El Rassi, Ziad

    2009-01-01

    Neutral diol methacrylate-based monoliths were developed for normal phase chromatography (NPC) and NP-CEC of polar compounds including N-glycans. Four different diol methacrylate-based monoliths were synthesized via the copolymerization of a functional monomer using either glyceryl monomethacrylate (GMM) or glycidyl methacrylate (GMA) and a crosslinker either ethylene dimethacrylate (EDMA) or trimethylolpropane trimethacrylate (TRIM). While the GMM-based monoliths yield in one reaction step polar diol methacrylate monoliths that are ready for use in NPC or NP-CEC, the GMA-based monoliths required a postmodification with hot sulfuric acid to convert the epoxy functions into diols before use in NPC or NP-CEC. All the four monoliths are neutral and void of fixed charges on their surfaces but yet exhibited relatively strong EOF in NP-CEC. The EOF is attributed to the adsorption of ions from the mobile phase thus forming the electric double layer necessary for producing a bulk mobile phase flow. Under the same in situ copolymerization conditions of GMM or GMA with either EDMA or TRIM, the GMM-EDMA monolith was the best choice in terms of retention, separation efficiency, EOF velocity in CEC and linear flow velocity in Nano-LC. PMID:19058161

  15. 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. PMID:24502271

  16. Magnetic solid lipid nanoparticles in hyperthermia against colon cancer.

    PubMed

    Muñoz de Escalona, María; Sáez-Fernández, Eva; Prados, José C; Melguizo, Consolación; Arias, José L

    2016-05-17

    A reproducible double emulsion/solvent evaporation procedure is developed to formulate magnetic solid lipid nanoparticles (average size≈180 nm) made of iron oxide cores embedded within a glyceryl trimyristate solid matrix. The physicochemical characterization of the nanocomposites ascertained the efficacy of the preparation conditions in their production, i.e. surface properties (electrokinetic and thermodynamic data) were almost indistinguishable from those of the solid lipid nanomatrix, while electron microscopy characterizations and X-ray diffraction patterns confirmed the satisfactory coverage of the magnetite nuclei. Hemocompatibility of the particles was established in vitro. Hysteresis cycle determinations defined the appropriate magnetic responsiveness of the nanocomposites, and their heating characteristics were investigated in a high frequency alternating gradient of magnetic field: a constant maximum temperature of 46 °C was obtained within 40 min. Finally, in vitro tests performed on human HT29 colon adenocarcinoma cells demonstrated a promising decrease in cell viability after treatment with the nanocomposites and exposure to that alternating electromagnetic field. To the best of our knowledge, this is the first time that such type of nanoformulation with very promising hyperthermia characteristics has been developed for therapeutic aims. PMID:26969080

  17. 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

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

    PubMed

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

    2016-12-01

    Bigels are biphasic systems formed by water-based hydrogels and oil-based organogels, mainly studied, in the last few years, for pharmaceutical and cosmetic application focused on the controlled delivery of both lipophilic and hydrophilic active agents. The rheological properties of bigels depend on both the amount and the rheological characteristics of single structured phases. Moreover, it can be expected that, at large fractions of one of the starting gels, systems more complex than oil-in-water or water-in-oil can be obtained, yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were investigated from a microstructural (i.e. microscopy and electrical conductivity tests) and rheological point of view. The hydrogel was prepared by using a low-methoxyl pectin whereas the organogel was prepared by using olive oil and, as gelator, a mixture of glyceryl stearate and policosanol. Model bigels were obtained by increasing the amount of organogel mixed with the hydrogel, and microstructural characterisation evidenced an organogel-in-hydrogel behaviour for all investigated samples, even though at the highest organogel content a more complex structure seems to arise. A semi-empirical model, based on theoretical equations developed for suspensions of elastic spheres in elastic media, was proposed to relate bigel rheological properties to single phase properties and fractions. PMID:27612723

  19. 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. PMID:26018337

  20. 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

  1. Galactosylated nanostructured lipid carriers for delivery of 5-FU to hepatocellular carcinoma.

    PubMed

    Varshosaz, Jaleh; Hassanzadeh, Farshid; Sadeghi, Hojjat; Khadem, Mostafa

    2012-09-01

    The aim of the present study was to design a targeted delivery system of 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). Lactobionic acid (LB) was conjugated to stearyl amine (SA) by a chemical reaction. The nanostructured lipid carriers (NLCs), containing LB conjugate, lecithin, glyceryl monostearate, oil [oleic acid (OA) or Labrafac 5 or 10%], and 5-FU, were dissolved in alcohol/acetone, the oil phase was added to the aqueous phase containing Tween 80 or Solutol(®) HS15 (0.25 or 0.5%), and NLCs were prepared by an emulsification-solvent diffusion method. Physical properties and drug release were studied in NLCs. The thiazolyl blue tetrazolium bromide assay was used to study the cytotoxicity of NLCs on HepG(2) cells, and the cellular uptake of NLCs was determined by flow cytometry. Fourier transform infrared spectroscopy and (1)H-NMR spectra confirmed the successful conjugation of LB and SA. The optimized NLCs consisted of 0.5% Solutol HS15 and 10% OA oil. The particle size of these nanoparticles was 139.2 nm, with a zeta potential of -18 mV, loading efficiency of 34.2%, release efficiency after 2 hours of the release test was 72.6%, and crystallinity was 0.63%. The galactosylated NLCs of 5-FU were cytotoxic on the HepG(2) cell line in a half concentration of 5-FU and seems promising in reducing 5-FU dose in HCC. PMID:22385296

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

    PubMed

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

    2013-04-01

    Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use. PMID:23715508

  3. Differences in the rheological properties and mixing compatibility with heparinoid cream of brand name and generic steroidal ointments: The effects of their surfactants

    PubMed Central

    Kitagawa, Shuji; Yutani, Reiko; Kodani, Rhu-ichi; Teraoka, Reiko

    2016-01-01

    Most steroidal ointments contain propylene glycol (PG) and surfactants, which improve the solubility of corticosteroids in white petrolatum. Surfactants aid the uniform dispersal of PG within white petrolatum. Since the surfactants used in generic ointments are usually different from those used in brand name ointments, we investigated the effects of surfactants on the rheological properties of three brand name ointments and six equivalent generic ointments. We detected marked differences in hardness, adhesiveness, and spreadability among the ointments. Further examinations of model ointments consisting of white petrolatum, PG, and surfactants revealed that the abovementioned properties, especially hardness and adhesiveness, were markedly affected by the surfactants. Since steroidal ointments are often admixed with moisturizing creams prior to use, we investigated the mixing compatibility of the ointments with heparinoid cream and how this was affected by their surfactants. We found that the ointments containing glyceryl monostearate demonstrated good mixing compatibility, whereas those containing non-ionic surfactants with polyoxyethylene chains exhibited phase separation. These results were also consistent with the findings for the model ointments, which indicates that the mixing compatibility of steroidal ointments with heparinoid cream is determined by the emulsifying capacity of the surfactants in their oily bases. PMID:26958460

  4. 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. PMID:24176347

  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. PMID:24502270

  6. Molecular cloning and phylogenetic analysis of Clonorchis sinensis elongation factor-1alpha.

    PubMed

    Kim, Tae Yun; Cho, Pyo Yun; Na, Jong Won; Hong, Sung-Jong

    2007-11-01

    Elongation factor-1 (EF-1) plays a primary role in protein synthesis, e.g., in the regulation of cell growth, aging, motility, embryogenesis, and signal transduction. The authors identified a clone CsIH23 by immunoscreening a Clonorchis sinensis cDNA library. The cDNA of CsIH23 was found to have a putative open reading frame containing 461 amino acids with a predicted molecular mass of 50.5 kDa. Its polypeptide sequence was highly homologous with EF-1alpha of parasites and vertebrate animals. CsIH23 polypeptide contained three GTP/GDP-binding sites, one ribosome-binding domain, one actin-binding domain, one tRNA-binding domain, and two glyceryl-phosphoryl-ethanolamine attachment sites. Based on these primary and secondary structural similarities, it was concluded that CsIH23 cDNA encodes C. sinensis EF-1alpha (CsEF-1alpha). In a molecular phylogenic tree, CsEF-1alpha clustered with the EF-1alpha of helminthic parasites. Subsequently, CsEF-1alpha recombinant protein was bacterially overexpressed and purified by Ni-NTA affinity column chromatography. Immunoblotting using CsEF-1alpha recombinant protein produced positive signals for all serum samples tested from clonorchiasis, opisthorchiasis viverinii, and paragonimiasis westermani patients and normal healthy controls. These findings suggest that recombinant CsEF-1alpha is of limited usefulness as serodiagnostic antigen for clonorchiasis. PMID:17674047

  7. 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. PMID:25934429

  8. 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

  9. 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.

  10. Effect of side-chain structure of rigid polyimide dispersant on mechanical properties of single-walled carbon nanotube/cyanate ester composite.

    PubMed

    Yuan, Wei; Li, Weifeng; Mu, Yuguang; Chan-Park, Mary B

    2011-05-01

    Three kinds of polymer, polyimide without side-chain (PI), polyimide-graft-glyceryl 4-nonylphenyl ether (PI-GNE), and polyimide-graft-bisphenol A diglyceryl acrylate (PI-BDA), have been synthesized and used to disperse single-walled carbon nanotubes (SWNTs) and to improve the interfacial bonding between SWNTs and cyanate ester (CE) matrix. Visual observation, UV-vis-near-IR (UV-vis-NIR) spectra, and atomic force microscopy (AFM) images show that both PI-GNE and PI-BDA are highly effective at dispersing and debundling SWNTs in DMF, whereas PI is less effective. Interaction between SWNTs and PI, PI-GNE or PI-BDA was confirmed by computer simulation and Raman spectra. A series of CE-based composite films reinforced with different loadings of SWNTs, SWNTs/PI, SWNTs/PI-GNE and SWNTs/PI-BDA were prepared by solution casting. It was found that, because of the unique side-chain structure of PI-BDA, SWNTs/PI-BDA disperse better in CE matrix than do SWNTs/PI-GNE, SWNTs/PI, and SWNTs. As a result, SWNTs/PI-BDA/CE composites have the greatest improvement in mechanical properties of the materials tested. These results imply that the choice of side-chain on a dispersant is very important to the dispersion of SWNTs in matrix and the filler/matrix interfacial adhesion, which are two key requirements for achieving effective reinforcement. PMID:21526794

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

    PubMed

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

    2016-01-01

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

  12. DUE PERMAFROST: A Circumpolar Remote Sensing Service for Permafrost - Evaluation Case Studies and Intercomparison with Regional Climate Model Simulations

    NASA Astrophysics Data System (ADS)

    Heim, Birgit; Bartsch, Annett; Elger, Kirsten; Rinke, Annette; Klehmet, Katharina; Matthes, Heidrun; Gellhorn, Catrin; Buchhorn, Marcel; Soliman, Aiman; Duguay, Claude

    2013-04-01

    The ESA Data User Element (DUE) Permafrost project provides a Circumpolar remote sensing service for permafrost-related applications. The data products are freely downloadable (http://www.ipf.tuwien.ac.at/permafrost) and published at the PANGAEA World Data Centre (DUE Permafrost Project Consortium, 2012). Remote sensing products are land surface temperature, surface soil moisture, ground frozen/non frozen state, terrain parameters, land cover parameters, and surface waters. Snow parameters (snow extent and snow water equivalent) can be derived from the DUE project GlobSnow (http://www.globsnow.info). The time series of Circumpolar land surface temperature and surface soil moisture offer weekly and monthly averaged data products from 2007 to 2010, Circumpolar ground frozen/non frozen state is provided as daily dataset. The ongoing service will also include the time series of 2011 and 2012. The Circumpolar terrain and land cover products are static, e.g. the first Circumpolar Digital Elevation Model (DEM) north of 55° N with a spatial resolution of 100 m (S. Maurizio & T. Strozzi, 2012). Evaluation is crucial to test the scientific validity of the DUE Permafrost data products for high-latitude permafrost landscapes. The primary programme providing ground data is the Global Terrestrial Network for Permafrost (GTN-P) initiated by the International Permafrost Association (IPA) in the 1990s. The involvement of scientific stakeholders and the IPA, and the ongoing evaluation of the remote sensing derived products make the DUE Permafrost products widely accepted by the scientific community. Evaluation case studies of DUE Permafrost remote-sensing derived products (e.g., land surface temperature and ground frozen/non frozen state) show good agreement with ground data from GTN-P monitoring sites in Alaska and Siberia. The Helmholtz Climate Initiative REKLIM (Regionale Klimaänderungen/Regional climate change) is a climate research program where regional observations and

  13. Internationally coordinated glacier monitoring: strategy and datasets

    NASA Astrophysics Data System (ADS)

    Hoelzle, Martin; Armstrong, Richard; Fetterer, Florence; Gärtner-Roer, Isabelle; Haeberli, Wilfried; Kääb, Andreas; Kargel, Jeff; Nussbaumer, Samuel; Paul, Frank; Raup, Bruce; Zemp, Michael

    2014-05-01

    Internationally coordinated monitoring of long-term glacier changes provide key indicator data about global climate change and began in the year 1894 as an internationally coordinated effort to establish standardized observations. Today, world-wide monitoring of glaciers and ice caps is embedded within the Global Climate Observing System (GCOS) in support of the United Nations Framework Convention on Climate Change (UNFCCC) as an important Essential Climate Variable (ECV). The Global Terrestrial Network for Glaciers (GTN-G) was established in 1999 with the task of coordinating measurements and to ensure the continuous development and adaptation of the international strategies to the long-term needs of users in science and policy. The basic monitoring principles must be relevant, feasible, comprehensive and understandable to a wider scientific community as well as to policy makers and the general public. Data access has to be free and unrestricted, the quality of the standardized and calibrated data must be high and a combination of detailed process studies at selected field sites with global coverage by satellite remote sensing is envisaged. Recently a GTN-G Steering Committee was established to guide and advise 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. Several online databases containing a wealth of diverse data types having different levels of detail and global coverage provide fast access to continuously updated information on glacier fluctuation and inventory data. For world-wide inventories, data are now available through (a) the World Glacier Inventory containing tabular information of about 130,000 glaciers covering an area of around 240,000 km2, (b) the GLIMS-database containing digital outlines of around 118,000 glaciers with different time stamps and

  14. ESA Data User Element PERMAFROST: a spaceborne permafrost monitoring and information system

    NASA Astrophysics Data System (ADS)

    Bartsch, A.; Heim, B.; Boike, J.; Elger, K.; Muster, S.; Langer, M.; Westermann, S.; Sobiech, J.

    2010-12-01

    Permafrost is a subsurface phenomenon whose ground thermal regime is mainly influenced by air temperature, land cover, soil and rock properties and snow parameters. Many spaceborne applications are potentially indicative for the thermal state of Permafrost, such as ‘land surface temperature’, ‘surface moisture’, ‘freeze/thaw’, ‘terrain’, ‘vegetation’ and ‘changes of surface waters’. The major task of the ESA Data User Element Permafrost project is to develop circumarctic/-boreal Earth Observation services of these parameters with extensive involvement of the permafrost research community The DUE PERMAFROST datasets will be processed in the EO-PERMAFROST Information System and provided via a WebGIS-interface. Further information is available at www.ipf.tuwien.ac.at/ permafrost. In order to set up the required validation tasks and information services, a target area approach with specified case study regions is used. Most of the foreseen DUE PERMAFROST remote sensing applications are well established and can optimally become operational. The goal of DUE PERMAFROST is to lend confidence in their scientific utility for high-latitude permafrost landscapes. Therefore, a major component is the evaluation of the DUE PERMAFROST products. Ground measurements in the high-latitude landscapes involve challenging logistics and are networked on multidisciplinary and circum-arctic level by the Permafrost community. The International Permafrost Association (IPA) has built up the Global Terrestrial Network for Permafrost (GTN-P) that is a network of the Circumpolar Active Layer Monitoring (CALM) and the Thermal State of Permafrost (TSP) projects. A major part of the DUE PERMAFROST core User group is contributing to GTN-P. Additional members of these programs and circum-arctic networks have also been involved in the consulting process and ground data providing process. Match-up data sets of ground data and remote sensing products coincident in time and

  15. Characterization and phylogenetic relationships among microsporidia infecting silkworm, Bombyx mori, using inter simple sequence repeat (ISSR) and small subunit rRNA (SSU-rRNA) sequence analysis.

    PubMed

    Rao, S Nageswara; Nath, B Surendra; Saratchandra, B

    2005-06-01

    This study is the first report on the genetic characterization and relationships among different microsporidia infecting the silkworm, Bombyx mori, using inter simple sequence repeat PCR (ISSR-PCR) analysis. Six different microsporidians were distinguished through molecular DNA typing using ISSR-PCR. Thus, ISSR-PCR analysis can be a powerful tool to detect polymorphisms and identify microsporidians, which are difficult to study with microscopy because of their extremely small size. Of the 100 ISSR primers tested, only 28 primers had reproducibility and high polymorphism (93%). A total of 24 ISSR primers produced 55 unique genetic markers, which could be used to differentiate the microsporidians from each other. Among the 28 SSRs tested, the most abundant were (CA)n, (GA)n, and (GT)n repeats. The degree of band sharing was used to evaluate genetic similarity between different microsporidian isolates and to construct a phylogenetic tree using Jaccard's similarity coefficient. The results indicate that the DNA profiles based on ISSR markers can be used as diagnostic tools to identify different microsporidia with considerable accuracy. In addition, the small subunit ribosomal RNA (SSU-rRNA) sequence gene was amplified, cloned, and sequenced from each of the 6 microsporidian isolates. These sequences were compared with 20 other microsporidian SSU-rRNA sequences to develop a phylogenetic tree for the microsporidia isolated from the silkworms. This method was found to be useful in establishing the phylogenetic relationships among the different microsporidians isolated from silkworms. Of the 6 microsporidian isolates, NIK-1s revealed an SSU-rRNA gene sequence similar to Nosema bombycis, indicating that NIK-1s is similar to N. bombycis; the remaining 5 isolates, which differed from each other and from N. bombycis, were considered to be different variants belonging to the species N. bombycis. PMID:16121233

  16. Analysis Of Ductile Crack Growth In Pipe Test In STYLE Project

    SciTech Connect

    Yin, Shengjun; Williams, Paul T; Klasky, Hilda B; Bass, Bennett Richard

    2012-01-01

    The Oak Ridge National Laboratory (ORNL) is conducting structural analyses, both deterministic and probabilistic, to simulate a large scale mock-up experiment planned within the European Network for Structural Integrity for Lifetime Management non-RPV Components (STYLE). The paper summarizes current ORNL analyses of STYLE s Mock-up3 experiment to simulate/evaluate ductile crack growth in a cladded ferritic pipe. Deterministic analyses of the large-scale bending test of ferritic surge pipe, with an internal circumferential crack, are simulated with a number of local micromechanical approaches, such as Gurson-Tvergaard-Needleman (GTN) model and cohesive-zone model. Both WARP 3D and ABAQUS general purpose finite element programs are being used to predict the failure load and the failure mode, i.e. ductile tearing or net-section collapse, as part of the pre-test phase of the project. Companion probabilistic analyses of the experiment are utilizing the ORNL developed open-source Structural Integrity Assessment Modular - Probabilistic Fracture Mechanics (SIAM-PFM) framework. SIAM-PFM contains engineering assessment methodology such as the tearing instability (J-T analysis) module developed for inner surface cracks under bending load. The driving force J-integral estimations are based on the SC.ENG1 or SC.ENG2 models. The J-A2 methodology is used to transfer (constraint-adjust) J-R curve material data from standard test specimens to the Mock-up3 experiment configuration. The probabilistic results of the Mock-Up3 experiment obtained from SIAM-PFM will be compared to those generated using the deterministic finite element modeling approach. The objective of the probabilistic analysis is to provide uncertainty bounds that will assist in assessing the more detailed 3D finite-element solutions and to also assess the level of confidence that can be placed in the best-estimate finite-element solutions.

  17. Satellite data acquisition requirements for monitoring of permafrost in polar regions

    NASA Astrophysics Data System (ADS)

    Bartsch, Annett

    2015-04-01

    Requirements for space based monitoring of permafrost features had been already defined within the IGOS Cryosphere Theme Report at the start of the IPY in 2007 (IGOS, 2007). In 2012 the Polar Space Task Group (PSTG, http://www.wmo.int/pages/prog/sat/pstg_en.php) has been established as the coordinating body of space agencies, in particular the Space Task Group (STG), for space -based observations of Polar Regions after the International Polar Year (IPY) and under the auspices of the World Meteorological Organization's (WMO) Executive Council Panel of Experts on Polar Observations Research and Services (EC-PORS). The PSTG identified the need to review the requirements for permafrost monitoring and to update these requirements as necessary in 2013. Relevant surveys with focus on satellite data are already available from the ESA DUE Permafrost User requirements survey (2009), the United States National Research Council (2014) and the ESA - CliC - IPA - GTN -P workshop in February 2014. These reports have been reviewed and specific needs discussed within the community. Acquisition requirements for monitoring of especially terrain changes (incl. rock glaciers and coastal erosion) and lakes (extent, ice properties etc.) with respect to current satellite missions have been specified. Of special interest for these applications are SAR missions. Current acquisition strategies for space borne SAR data only partially cover polar permafrost regions and some of the longterm in-situ measurement sites. Many stations are located in the proximity to coastal areas and glaciers which to some extent may allow joint usage by different cryosphere applications but requirements may deviate. The results of the discussion are presented in this paper.

  18. GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

    SciTech Connect

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Wang, Yuan-Hung; Hsieh, Yi-Chen; Lien, Li-Ming; Lee, Te-Chang; Chen, Chien-Jen

    2010-11-01

    Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, and peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele ({>=} 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure.

  19. Sequence of human tryptophan 2,3-dioxygenase (TDO2): Presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat

    SciTech Connect

    Comings, D.E.; Muhleman, D.; Dietz, G.

    1995-09-20

    Abnormalities in serotonin levels have been implicated in a wide range of psychiatric disorders. Tryptophan 2,3-dioxygenase is the rate-limiting enzyme in the catabolism of tryptophan, the precursor of serotonin. As such it is a potential major candidate gene in psychiatric genetics. The regulatory, intron, and exon regions of the human TDO2 gene have been sequenced. Twelve exons were identified. The amino acid sequence of the enzyme was 88% homologous to that of the rat. Compared to the rat, the regulatory region of the human TDO2 gene had an insertion of approximately 1064 bp of random DNA beginning at -293 bp and extending to -1357 bp. This displaced the glucocorticoid response element (GRE) occurring at -1174 bp in the rat to -1500 in the human. The proximal GRE at -419 in the rat was missing in the human. However, within the DNA insert there was a GRE-like microsatellite region containing multiple GTT repeats plus additional GT(n) sequences. This could produce several staggered regions of the sequence TGTTGTnnnTGTTGT similiar to a GRE consensus sequence of TGTTCAnnnTGTTCT. The intron regions 5` and 3` to each exon were sequenced. This allowed each exon to be screened for mutations. This showed a His{r_arrow}Val mutation polymorphism in exon 7. Three introns, 1, 5, and 6, were completely sequenced and examined for polymorphisms. This identified two polymorphisms consisting of G{r_arrow}T and G{r_arrow}A mutations 2 bp apart in intron 6. The 3` end of intron 5` showed an extensive CCCCT pentanucleotide repeat that was markedly polymorphic. These polymorphisms allow the TDO2 gene to be examined for a possible role in psychiatric disorders. 35 refs., 4 figs., 1 tab.

  20. XMM-Newton Education and Public Outreach Program

    NASA Astrophysics Data System (ADS)

    Plait, P.; Silva, S.; Graves, T.; Simonnet, A.; Cominsky, L.

    2004-08-01

    XMM-Newton is a joint NASA-European Space Agency (ESA) orbiting observatory, designed to observe high energy X-rays emitted from exotic astronomical objects such as pulsars, black holes, and active galaxies. It was launched on December 10, 1999 from the ESA base at Kourou, French Guiana and continues to make observations today. In 2003, The NASA E/PO Group at Sonoma State University took the lead for the US portion of the XMM-Newton Education and Public Outreach (E/PO) program. This program is using the mission science to engage students in learning science and mathematics. Currently we are working on developing an educator's unit for grades 6-12 using supernovae to teach the origin of the chemical elements. With the Contemporary Laboratory Experiences in Astronomy (CLEA) group at Gettysburg College, we are developing an interactive laboratory exploring elemental abundances through the X-ray spectroscopy of a supernova remnant. The XMM-Newton E/PO program has also partnered with the GLAST Telescope Network (GTN) and the AAVSO to help coordinate observations of magnetic white dwarfs called polars. In addition, we are creating a Starlab Planetarium show which will compare and contrast the X-ray and visible light skies. The outreach program has created a website (mirrored at NASA's Goddard Space Flight Center) designed to enhance the XMM-Newton mission's science education. More educational materials and information about the XMM-Newton E/PO program can be found at http://xmm.sonoma.edu.

  1. NORPERM, the Norwegian Permafrost Database - a TSP NORWAY IPY legacy

    NASA Astrophysics Data System (ADS)

    Juliussen, H.; Christiansen, H. H.; Strand, G. S.; Iversen, S.; Midttømme, K.; Rønning, J. S.

    2010-10-01

    NORPERM, the Norwegian Permafrost Database, was developed at the Geological Survey of Norway during the International Polar Year (IPY) 2007-2009 as the main data legacy of the IPY research project Permafrost Observatory Project: A Contribution to the Thermal State of Permafrost in Norway and Svalbard (TSP NORWAY). Its structural and technical design is described in this paper along with the ground temperature data infrastructure in Norway and Svalbard, focussing on the TSP NORWAY permafrost observatory installations in the North Scandinavian Permafrost Observatory and Nordenskiöld Land Permafrost Observatory, being the primary data providers of NORPERM. Further developments of the database, possibly towards a regional database for the Nordic area, are also discussed. The purpose of NORPERM is to store ground temperature data safely and in a standard format for use in future research. The IPY data policy of open, free, full and timely release of IPY data is followed, and the borehole metadata description follows the Global Terrestrial Network for Permafrost (GTN-P) standard. NORPERM is purely a temperature database, and the data is stored in a relation database management system and made publically available online through a map-based graphical user interface. The datasets include temperature time series from various depths in boreholes and from the air, snow cover, ground-surface or upper ground layer recorded by miniature temperature data-loggers, and temperature profiles with depth in boreholes obtained by occasional manual logging. All the temperature data from the TSP NORWAY research project is included in the database, totalling 32 temperature time series from boreholes, 98 time series of micrometeorological temperature conditions, and 6 temperature depth profiles obtained by manual logging in boreholes. The database content will gradually increase as data from previous and future projects are added. Links to near real-time permafrost temperatures, obtained

  2. Separation of Rebaudiana A from Steviol glycoside using a polymeric adsorbent with multi-hydrogen bonding in a non-aqueous system.

    PubMed

    Ba, Jing; Zhang, Na; Yao, Lijuan; Ma, Ning; Wang, Chunhong

    2014-11-15

    Rebaudioside A (RA) and stevioside (SS) are the primary effective glycoside components in Stevia Rebaudiana. The RA glycoside is sweeter, and it tastes similarly to sucrose. Because extracts with a high RA content can be used as natural sweeteners for food additives approved by the FAO and FDA, RA should generate high market demand. In this study, an efficient method for separating RA was established based on the synergistic multi-hydrogen bonding interaction between a polymeric adsorbent and the RA glycoside. To overcome the destruction of the hydrophobic affinity required for the selective adsorption of RA, an innovative non-aqueous environment was established for adsorption and separation. To this end, an initial polymeric adsorbent composed of a glycidyl methacrylate and trimethylolpropane trimethacrylate (GMA-co-TMPTMA) copolymer matrix was synthesized, and polyethylene polyamine was employed as a functional reagent designed to react with the epoxy group on GME-co-TMPTMA to form a highly selective macroporous adsorbent. The effects of the different functional reagents and the solvent polarity on the adsorption selectivity for RA and SS, respectively, were investigated. Matching the structure of the polyethylene polyamine and sugar ligand on the glycoside molecule was essential in ensuring that the maximum synergistic interaction between adsorbent and adsorbate would be achieved. Moreover, the hydrogen-bonding force was observed to increase when the polarity of the adsorption solvent decreased. Therefore, among the synthesized macroporous polymeric adsorbents, the GTN4 adsorbent-bonding tetraethylenepentamine functional group provided the best separation in an n-butyl alcohol solution. Under the optimized gradient elution conditions, RA and SS can be effectively separated, and the contents of RA and SS increased from 33.5% and 51.5% in the initial crude extract to 95.4% and 78.2% after separation, respectively. Compared to conventional methods, the adsorption

  3. Heterologous gene expression driven by carbonic anhydrase gene promoter in Dunaliella salina

    NASA Astrophysics Data System (ADS)

    Chai, Yurong; Lu, Yumin; Wang, Tianyun; Hou, Weihong; Xue, Lexun

    2006-12-01

    Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaCl. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficient promoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5' franking region of 1.4 kb from the carbonic anhydrase ( CAH) gene of D. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem (GT)n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site (TSS) of the CAH gene was determined by 5' RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar (bialaphos resistance) gene when the fusion was transformed into D. salina by biolistics. Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.

  4. Dystonia in Ashkenazi Jews: clinical characterization of a founder mutation.

    PubMed

    Bressman, S B; de Leon, D; Kramer, P L; Ozelius, L J; Brin, M F; Greene, P E; Fahn, S; Breakefield, X O; Risch, N J

    1994-11-01

    A gene (DYT1) for idiopathic torsion dystonia maps to chromosome 9q34 in Ashkenazi Jewish families with early onset of symptoms. Further, there is linkage disequilibrium between DYT1 and a particular haplotype of alleles at 9q34 loci in this population. This implies that a large proportion of early-onset idiopathic torsion dystonia in Ashkenazi Jews is due to a founder mutation in DYT1. To characterize the phenotypic range of this mutation, we studied 174 Ashkenazi Jewish individuals affected with idiopathic torsion dystonia. We used GT(n) markers on chromosome 9q34 (D9S62, D9S63, and ASS) and classified individuals as having ("carriers"), not having ("noncarriers"), or being ambiguous with respect to a DYT1-associated haplotype. We assessed clinical features and found marked clinical differences between haplotype carriers and noncarriers. There were 90 carriers, 70 noncarriers, and 14 ambiguous individuals. The mean age at onset of symptoms was significantly lower in carriers than in noncarriers (12.5 +/- 8.2 vs 36.5 +/- 16.4 years). In 94% of carriers, symptoms began in a limb (arm or leg equally); rarely the disorder started in the neck (3.3%) or larynx (2.2%). In contrast, the neck, larynx, and other cranial muscles were the sites of onset in 79% of noncarriers; onset in the arms occurred in 21% and onset in the legs never occurred. Limb onset, leg involvement in the course of disease, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In conclusion, there are clinical differences between Ashkenazi Jewish individuals with idiopathic torsion dystonia who do or do not have a unique DYT1 mutation, as determined by a DYT1-associated haplotype of 9q34 alleles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7979224

  5. RECENT DEVELOPMENTS IN HYDROWEB DATABASE Water level time series on lakes and reservoirs (Invited)

    NASA Astrophysics Data System (ADS)

    Cretaux, J.; Arsen, A.; Calmant, S.

    2013-12-01

    We present the current state of the Hydroweb database as well as developments in progress. It provides offline water level time series on rivers, reservoirs and lakes based on altimetry data from several satellites (Topex/Poseidon, ERS, Jason-1&2, GFO and ENVISAT). The major developments in Hydroweb concerns the development of an operational data centre with automatic acquisition and processing of IGDR data for updating time series in near real time (both for lakes & rivers) and also use of additional remote sensing data, like satellite imagery allowing the calculation of lake's surfaces. A lake data centre is under development at the Legos in coordination with Hydrolare Project leaded by SHI (State Hydrological Institute of the Russian Academy of Science). It will provide the level-surface-volume variations of about 230 lakes and reservoirs, calculated through combination of various satellite images (Modis, Asar, Landsat, Cbers) and radar altimetry (Topex / Poseidon, Jason-1 & 2, GFO, Envisat, ERS2, AltiKa). The final objective is to propose a data centre fully based on remote sensing technique and controlled by in situ infrastructure for the Global Terrestrial Network for Lakes (GTN-L) under the supervision of WMO and GCOS. In a longer perspective, the Hydroweb database will integrate data from future missions (Jason-3, Jason-CS, Sentinel-3A/B) and finally will serve for the design of the SWOT mission. The products of hydroweb will be used as input data for simulation of the SWOT products (water height and surface variations of lakes and rivers). In the future, the SWOT mission will allow to monitor on a sub-monthly basis the worldwide lakes and reservoirs bigger than 250 * 250 m and Hydroweb will host water level and extent products from this

  6. Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13; 14) trisomy 14

    SciTech Connect

    Antonarakis, S.E.; Blouin, J.L.; Maher, J.; Avramopoulos, D.; Thomas, G.; Talbot, C.C. Jr. )

    1993-06-01

    Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. The authors recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hyperchloesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, they have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14. There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed -- and subsequent cytogenetic analysis confirmed -- that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a [open quotes]maternal UPD chromosome 14 syndrome[close quotes] is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes. 33 refs., 3 figs., 1 tab.

  7. Formalised consensus of the European Organisation for Treatment of Trophoblastic Diseases on management of gestational trophoblastic diseases.

    PubMed

    Bolze, Pierre-Adrien; Attia, Jocelyne; Massardier, Jérôme; Seckl, Michael J; Massuger, Leon; van Trommel, Nienke; Niemann, Isa; Hajri, Touria; Schott, Anne-Marie; Golfier, François

    2015-09-01

    Gestational trophoblastic disease (GTD) is a spectrum of cellular proliferations arising from trophoblast. Their invasive and metastatic potential sometimes requires chemotherapy and/or surgery. Current management is generally associated with favourable prognosis. Therefore, treatments must be chosen according to the desire for further childbearing of each patient. The European Organisation for Treatment of Trophoblastic Diseases (EOTTD) is dedicated to optimise diagnosis, treatment, follow-up and research in GTD by bringing together knowledge of clinicians and researchers from 29 countries working in the field of GTD in Europe. This study assessed the level of agreement among an expert panel of the EOTTD in order to rationalise the management of patients in Europe. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results. There was an agreement for 54 statements while the experts showed a disagreement for two statements. As there is little evidence from randomised trials on which to base recommendations about management of GTD, many of these recommendations are based on expert opinion derived from changes in management fact that have improved outcomes from nearly 100% fatality to nearly 100% cure rates. However, a large agreement among experts is invaluable to the individual clinician who is struggling to decide whether a fertility-sparing treatment of hydatidiform mole or a low-risk GTN can be chosen and how it must be conducted. PMID:26092638

  8. Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

    PubMed

    Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

    2015-08-01

    Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. PMID:25869522

  9. Haplotypes of angiotensinogen in essential hypertension.

    PubMed Central

    Jeunemaitre, X; Inoue, I; Williams, C; Charru, A; Tichet, J; Powers, M; Sharma, A M; Gimenez-Roqueplo, A P; Hata, A; Corvol, P; Lalouel, J M

    1997-01-01

    The M235T polymorphism of the angiotensinogen gene (AGT) has been associated with essential and pregnancy-induced hypertension. Generation of haplotypes can help to resolve whether the T235 allele itself predisposes to the development of hypertension or acts as a marker of an unknown causal molecular variant. We identified 10 diallelic polymorphisms at the AGT locus and genotyped both a series of 477 probands of hypertensive families and 364 controls, all French Caucasians, as well as a series of 92 hypertensives and 122 controls from Japan. Despite a large ethnic difference in gene frequency, a significant association of T235 with hypertension was observed both in Cancasians (.46 vs. .38, P = .004) and in Japanese (.91 vs. .76, P = .002). In both groups, the G-->A substitution located at position -6 upstream of the initial transcription site occurred at the same frequency and in complete linkage disequilibrium with the T235 allele. No other polymorphism was found to be consistently associated with hypertension. Five informative haplotypes subdividing the T235 allele were generated. Whereas two of them were associated with hypertension in Caucasians, none of these two haplotypes (H3 and H4) reached statistical significance in Japanese. The analysis of the AGT-GT repeat revealed marked linkage disequilibriums between each of the diallelic polymorphisms and some (GT)n alleles, with similar patterns in the two populations. The strong disequilibrium between M235 and (GT)16 explained the increased frequency of that particular allele in French controls compared with hypertensives (.42 vs. .36, P < .01). The haplotype combining the M235T and G-6A polymorphisms appears as the ancestral allele of the human AGT gene and as the one associated with hypertension. PMID:9199566

  10. 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.

  11. 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. PMID:26474244

  12. A short history of nitroglycerine and nitric oxide in pharmacology and physiology.

    PubMed

    Marsh, N; Marsh, A

    2000-04-01

    Moncada identified endothelial-derived relaxing factor (EDRF) as NO (in 1987). 9. Glycerol trinitrate remains the treatment of choice for relieving angina; other organic esters and inorganic nitrates are also used, but the rapid action of NG and its established efficacy make it the mainstay of angina pectoris relief. PMID:10779131

  13. Co-encapsulation of multi-lipids and polymers enhances the performance of vancomycin in lipid-polymer hybrid nanoparticles: In vitro and in silico studies.

    PubMed

    Seedat, Nasreen; Kalhapure, Rahul S; Mocktar, Chunderika; Vepuri, Suresh; Jadhav, Mahantesh; Soliman, Mahmoud; Govender, Thirumala

    2016-04-01

    Nano-drug delivery systems are being widely explored to overcome the challenges with existing antibiotics to treat bacterial infections [1]. Lipid-polymer hybrid nanoparticles (LPNs) display unique advantages of both liposomes and polymeric nanoparticles while excluding some of their limitations, particularly the structural integrity of the polymeric particles and the biomimetic properties of the liposome [1]. The use of helper lipids and polymers in LPNs has not been investigated, but has shown potential in other nano-drug delivery systems to improve drug encapsulation, antibacterial activity and drug release. Therefore, LPNs using co-excipients were prepared using vancomycin (VCM), glyceryl triplamitate and Eudragit RS100 as the drug, lipid and polymer respectively. Oleic acid (OA), Chitosan (CHT) and Sodium alginate (ALG) were explored as co-excipients. Results indicated rod-shaped LPNs with suitable size, PDI and zeta potential, while encapsulation efficiency (%EE) increased from 27.8% to 41.5%, 54.3% and 69.3% with the addition of OA, CHT and ALG respectively. Drug release indicated that VCM-CHT had the best performance in sustained drug release of 36.1 ± 5.35% after 24h. The EE and drug release were further corroborated by in silico and release kinetics data. In vitro antibacterial studies of all formulations exhibited better activity against bare VCM and sustained activity up to day 5 against both Staphylococcus aureus and MRSA, with VCM-OA and VCM-CHT showing better activity against MRSA. Therefore, this LPN proves to be a promising system for delivery of VCM as well as other antibiotics. PMID:26838890

  14. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

    PubMed Central

    Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

    2013-01-01

    Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

  15. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  16. Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

    PubMed

    Lee, Kathy W Y; Nguyen, Tri-Hung; Hanley, Tracey; Boyd, Ben J

    2009-01-01

    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system. PMID:18790030

  17. Carrier-mediated ion transport in lipid bilayer membranes.

    PubMed

    Laprade, R; Grenier, F; Pagé-Dansereau, M; Dansereau, J

    1984-08-01

    The electrical properties predicted by a widely accepted model for carrier-mediated ion transport in lipid bilayers are described. The different steps leading to ion transport and their associated rate constants are reaction at the interface between an ion in the aqueous phase and a carrier in the membrane (kRi), followed by translocation of the ion-carrier complex across the membrane interior (kis) and its dissociation at the other interface (kDi) after which the free carrier crosses back the membrane interior (ks). Results on glyceryl monooleate (GMO) membranes for a family of homologue carriers, the macrotetralide actin antibiotics (nonactin, monactin, dinactin, trinactin, and tetranactin) and a variety of ions (Na+, Cs+, Rb+, K+, NH4+, and Tl+) are presented. Internally consistent data obtained from steady-state electrical measurements (zero-current potential and conductance, current-voltage relationship) allow us to obtain the equilibrium permeability ratios for the different ions and show that for a given carrier kRi is relatively invariant from one ion to the other, except for Tl+ (larger), which implies that the ionic selectivity is controlled by the dissociation of the complex. The values of the individual rate constants obtained from current relaxation experiments are also presented and confirm the findings from steady-state measurements, as well as the isostericity concept for complexes of different ions with the same carrier (kis invariant). These also allow us to determine the aqueous phase membrane and torus membrane partition coefficients. Finally, the observed increase in kis from nonactin to tetranactin and, for all homologues, from GMO-decane to solvent-free GMO membranes, together with the concomitant decrease in kDi, can be explained in terms of modifications of electrostatic energy profiles induced by variations in carrier size and membrane thickness. PMID:6498590

  18. A lipid-based liquid crystalline matrix that provides sustained release and enhanced oral bioavailability for a model poorly water soluble drug in rats.

    PubMed

    Boyd, Ben J; Khoo, Shui-Mei; Whittaker, Darryl V; Davey, Greg; Porter, Christopher J H

    2007-08-01

    Liquid crystalline phases that are stable in excess water, formed using lipids such as glyceryl monooleate (GMO) and oleyl glycerate (OG), are known to provide a sustained release matrix for poorly water soluble drugs in vitro, yet there has been no report of the use of these materials to impart oral sustained release behaviour in vivo. In the first part of this study, in vitro lipolysis experiments were used to compare the digestibility of GMO with a second structurally related lipid, oleyl glycerate, which was found to be less susceptible to hydrolysis by pancreatic lipase than GMO. Subsequent oral bioavailability studies were conducted in rats, in which a model poorly water soluble drug, cinnarizine (CIN), was administered orally as an aqueous suspension, or as a solution in GMO or OG. In the first bioavailability study, plasma samples were taken over a 30 h period and CIN concentrations determined by HPLC. Plasma CIN concentrations after administration in the GMO formulation were only sustained for a few hours after administration while for the OG formulation, the plasma concentration of cinnarizine was at its highest level 30 h after dosing, and appeared to be increasing. A second study in which CIN was again administered in OG, and plasma samples taken for 120 h, revealed a Tmax for CIN in rats of 36 h and a relative oral bioavailability of 344% when compared to the GMO formulation (117%) and the aqueous suspension formulation (assigned a nominal bioavailability of 100%). The results indicate that lipids that form liquid crystalline structures in excess water, may have application as an oral sustained release delivery system, providing they are not digested rapidly on administration. PMID:17467935

  19. Disposition and association of the steric stabilizer Pluronic® F127 in lyotropic liquid crystalline nanostructured particle dispersions.

    PubMed

    Tilley, Adam J; Drummond, Calum J; Boyd, Ben J

    2013-02-15

    Liquid crystalline nanostructured particles, such as cubosomes and hexosomes, are most often colloidally stabilised using the tri-block co-polymer Pluronic® F127. Although the effect of F127 on the internal particle nanostructure has been well studied, the associative aspects of F127 with cubosomes and hexosomes are poorly understood. In this study the quantitative association of F127 with phytantriol-based cubosomes and hexosomes was investigated. The amount of free F127 in the dispersions was determined using pressure ultra-filtration. The percentage of F127 associated with the particles plateaued with increasing F127 concentration above the critical aggregation concentration. Hence the free concentration of F127 in the dispersion medium was proposed as a key factor governing association below the CMC, and partitioning of F127 between micelles and particles occurred above the CMC. The association of F127 with the particles was irreversible on dilution. The F127 associated with both the external and internal surfaces of the phytantriol cubosomes. The effects of lipid and F127 concentration, lipid type, dilution of the dispersions and internal nanostructure were also elucidated. A greater amount of F127 was associated with cubosomes comprised of glyceryl monooleate (GMO) than those prepared using phytantriol. Hexosomes prepared using a mixture of phytantriol and vitamin E acetate (vitEA) had a greater amount of F127 associated with them than phytantriol cubosomes. Hexosomes prepared using selachyl alcohol had less F127 associated with them than phytantriol:vitEA-based hexosomes and GMO-based cubosomes. This indicated that both the lipid from which the particles are composed and the particle internal nanostructure have an influence on the association of F127 with lyotropic liquid crystalline nanostructured particles. PMID:23137909

  20. Influence of type and level of water-soluble additives on drug release and surface and mechanical properties of Surelease films.

    PubMed

    Rohera, Bhagwan D; Parikh, Nilesh H

    2002-11-01

    Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats. PMID:12503524