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Sample records for glyceryl trinitrate gtn

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Glyceryl trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine...

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

    NARCIS (Netherlands)

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

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

  3. Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

    DEFF Research Database (Denmark)

    Hauerslev, Marie; Mørk, Sivagowry Rasalingam; Pryds, Kasper

    2018-01-01

    Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Due to overlapping mechanisms this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term ...

  4. Intracranial hemodynamics during intravenous infusion of glyceryl trinitrate

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  5. Effect of transdermal glyceryl trinitrate and anti-inflammatory gel in infusion phlebitis.

    Science.gov (United States)

    Cökmez, Atilla; Gür, Serhat; Genç, Hüdai; Deniz, Sümer; Tarcan, Ercüment

    2003-10-01

    Phlebitis is the commonest complication of intravenous infusion. It has been suggested that it is initiated by venoconstriction at the infusion site, hence treatment with a vasodilator may reduce its incidence. A prospective controlled study was carried out on the effect of transdermal glyceryl trinitrate (GTN) and topical anti-inflammatory gel (non-steroidal anti-inflammatory drug; NSAID) on the survival of peripheral intravenous infusion in 386 patients. A total of 34.9% (43 out of 123) of the infusions failed in the control group compared with 14.1% (18 out of 127) in the NSAID group (P NSAI gel and GTN but NSAI gel is more effective than GTN.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 [ 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 [ 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

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

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    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 μM 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Eva Maria Augusta Boeckh Haebisch

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

  10. Mechanisms of glyceryl trinitrate provoked mast cell degranulation

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. Chemical colostomy irrigation with glyceryl trinitrate solution.

    Science.gov (United States)

    O'Bichere, A; Bossom, C; Gangoli, S; Green, C; Phillips, R K

    2001-09-01

    Colostomy irrigation may improve patient quality of life, but is time consuming. This study tests the hypothesis that irrigation with glyceryl trinitrate solution, by inducing gastrointestinal smooth muscle relaxation, may accelerate expulsion of stool by passive emptying, thereby reducing irrigation time. Fifteen colostomy irrigators(with more than 3 years' experience) performed washout with tap water compared with water containing 0.025 mg/kg glyceryl trinitrate. Fluid inflow time, total washout time, and hemodynamic changes occurring during glyceryl trinitrate irrigation were documented by an independent observer. Subjects recorded episodes of fecal leakage and overall satisfaction on a visual analog scale. Cramps, headaches, and whether or not a stoma bag was used were expressed as a percentage of number of irrigations. Comparison of fluid inflow time, total washout time, leakage, and satisfaction was by Wilcoxon's signed-rank test and headaches, cramps, and stoma bag use was by McNemar's test. Pulse rate (paired t-test), systolic and diastolic blood pressures (Wilcoxon's test) at 20 and 240 minutes after washout with glyceryl trinitrate solution were compared with baseline. Fifteen patients (9 female), with a mean age of 53 (31-73) years, provided 30 sessions (15 with water and 15 with glyceryl trinitrate). Medians (interquartile ranges) for water vs. glyceryl trinitrate were fluid inflow time 7 (4-10) vs. 4, (3-5; P = 0.001); total washout time 40 (30-55) vs. 21, (15-24; P colostomy irrigation time compared with the generally recommended tap water. Patients suffer fewer leakages and are highly satisfied, but side effects are potential drawbacks. Other colonoplegic agent solutions should now be evaluated.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    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...... 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....

  13. Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate

    DEFF Research Database (Denmark)

    Woodhouse, Lisa J; Scutt, Polly; Hamdy, Shaheen

    2017-01-01

    Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial...... h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved...

  14. Topical glyceryl trinitrate for chronic Achilles tendinopathy.

    Science.gov (United States)

    Hunte, Garth; Lloyd-Smith, Rob

    2005-03-01

    To determine whether continuous application of topical glyceryl trinitrate decreases pain and symptoms in chronic noninsertional Achilles tendinopathy. Randomized double-blind placebo-controlled study of 6-months' duration. Community and referral study at an Australian University Hospital. Recruitment was through newspaper advertisements and private consulting rooms. Eligibility criteria were age >18 years, a history of insidious onset of Achilles tendon pain, a tender nodule localized to the region of the calcaneal insertion, and an ultrasound examination that excluded a tendon tear. Exclusion criteria were Achilles tendinopathy of calf muscle-strengthening program. At the baseline, 2, 6, 12, and 24-week examinations the patient completed a symptom assessment sheet to rate the severity of Achilles pain with activity, at rest, and at night (0 = no pain, 4 = very severe pain). The single assessor used the same scale to measure local tenderness; an 11-point scale for the patient to report pain after the single-leg 10-hop test; and also measured the ankle plantar flexor mean peak force and ankle plantar flexor work. Follow-up was 89% complete. The groups did not differ in pain with activity, night pain, or local tenderness until the 12-week assessment when participants in the glyceryl trinitrate group reported less pain on each measure (mean scores, 0.9 vs. 1.6 [P = 0.02]; 0.2 vs. 0.7 [P = 0.04]; and 0.9 vs. 1.6 [P = 0.02], respectively). The difference was maintained at 24 weeks for pain with activity (mean scores, 0.4 vs. 1.0 [P = 0.03]). At 24 weeks the glyceryl trinitrate group reported less pain on the 10-hop test than the placebo group (mean scores, 0.5 vs. 1.6 [P = 0.005]). Although the intervention group showed a greater increase in plantar flexor mean total work at 24 weeks than the placebo group, the baseline scores were significantly different. The groups did not differ in pain at rest or in ankle plantar flexor peak force. Combining all the measures showed

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

    Directory of Open Access Journals (Sweden)

    Yusuf Assem

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean......BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM......: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: ...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

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    Evgeny Pryazhnikov

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

  20. TO KNOW THE EFFICACY OF GLYCERYL TRINITRATE PATCH AND RITODRINE AS TOCOLYTIC AGENTS: A COMPARATIVE STUDY

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    Usharani

    2015-02-01

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

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

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    Jiexia Ding

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

  2. Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure.

    Science.gov (United States)

    Kocher, H M; Steward, M; Leather, A J M; Cullen, P T

    2002-04-01

    Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects. A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent. Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31). DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.

  3. Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris

    NARCIS (Netherlands)

    Gobel, EJAM; Hautvast, RWM; vanGilst, WH; Spanjaard, JN; Hillege, HL; DeJongste, MJL; Molhoek, GP; Lie, KI

    1995-01-01

    The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non- dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate. both given intravenously, in 129

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    . In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. Methods: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl...... trinitrate on these behaviors in female rats was observed. Results: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None...

  5. Endosonographic and manometric evaluation of internal anal sphincter in patients with chronic anal fissure and its correlation with clinical outcome after topical glyceryl trinitrate therapy.

    Science.gov (United States)

    Pascual, Marta; Pera, Miguel; Courtier, Ricard; Gil, Mariá José; Parés, David; Puig, Sonia; Andreu, Montserrat; Grande, Luis

    2007-08-01

    Anorectal pressure studies have demonstrated internal anal sphincter (IAS) hypertonia in patients with chronic anal fissure. It is unknown however, if these changes in IAS function are associated with any abnormality in sphincter morphology. The first aim was to investigate the clinical characteristics and the manometric and endosonographic findings of the IAS in a cohort of patients with chronic anal fissure. The second aim was to investigate the association between these findings and the outcome with topical Glyceryl trinitrate (GTN) therapy. All patients who presented with chronic anal fissure from November 1999 to May 2004 were included after failure of conservative therapy. Anorectal manometry and anal endosonography were performed before treatment with 0.2% GTN ointment twice daily was initiated. Patients were evaluated after 8 weeks. One hundred and twenty-four patients (66 women, mean age, 45.2 +/- 14.8 years) were included. Hypertonia of the IAS was found in 84 (68%) patients. The mean maximum IAS thickness was 3.6 +/- 0.76 mm (1.6-5.5). An abnormally thick IAS, adjusted by age, was observed in 113 (91.1%) patients. We found no correlation between resting pressure and IAS thickness (r = 0.074; p = 0.41). At 8 weeks, 52 patients (42%) had healed with complete symptoms resolution. No statistically significant differences were observed when clinical features and manometric and endosonographic findings were compared between healing and no-healing fissures. The majority of patients with chronic anal fissure present an abnormally thick IAS. Clinical, manometric and endosonographic features had no association with outcome after GTN treatment.

  6. 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

    Directory of Open Access Journals (Sweden)

    Philip M. Bath

    2016-01-01

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

  7. A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol.

    Science.gov (United States)

    Denison, Fiona C; Norrie, John; Lawton, Julia; Norman, Jane E; Scotland, Graham; McPherson, Gladys C; McDonald, Alison; Forrest, Mark; Hudson, Jemma; Brewin, Jane; Peace, Mathilde; Clarkson, Cynthia; Brook-Smith, Sheonagh; Morrow, Susan; Hallowell, Nina; Hodges, Laura; Carruthers, Kathryn F

    2017-09-18

    A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice. Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals. ISCRTN88609453; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  8. Glyceryl Trinitrate for Acute Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa

    2016-01-01

    if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome...... was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed...

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

    Science.gov (United States)

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

    2011-05-01

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

  10. Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study.

    Science.gov (United States)

    Ralph, David J; Eardley, Ian; Taubel, Jorg; Terrill, Paul; Holland, Tim

    2018-02-01

    Current treatments for erectile dysfunction (ED) have some limitations. This study evaluated the efficacy and tolerability of MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED. This randomized, double-blinded, placebo-controlled, phase II crossover trial involved 232 men with ED (231 treated, 230 assessed for efficacy) and their partners. After a 4-week run-in period, patients were randomized to 1 of 2 treatment sequences, MED2005-placebo or placebo-MED2005. Each treatment was given for 4 weeks, separated by a 1-week washout interval. Efficacy was assessed by the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, a Global Assessment Questionnaire (GAQ), and specific questions about the onset and offset of action and treatment preferences (patients and partners). The primary outcome measure was the IIEF erectile function domain (IIEF-EF) score. Other efficacy assessments were secondary outcomes. The mean baseline IIEF-EF score was 17.1 (SD = 5.7), and this increased to 19.6 (SD = 7.5) after MED2005 treatment and 18.5 (SD = 6.7) after placebo (P = .0132). Overall, 23.1% of patients showed a clinically relevant (≥4-point) increase in IIEF-EF scores after treatment with MED2005 only compared with 14.5% who responded after MED2005 and placebo, 14.0% who responded after placebo only, and 48.4% who did not respond after either treatment (P = .0272). MED2005 also was associated with significant improvements compared with placebo in the other IIEF domains, and this was consistent with patients' and partners' responses to the GAQ. For all assessments, significant effects of MED2005 were seen primarily in patients with mild ED. The start of erection was noticed within 5 and 10 minutes in 44.2% and 69.5%, respectively, of all intercourse attempts with MED2005. Patients and partners showed significant preferences for MED2005

  11. Coexisting typical migraine in familial hemiplegic migraine

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  12. Nitric oxide-related drug targets in headache

    DEFF Research Database (Denmark)

    Olesen, Jes

    2010-01-01

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

  13. "The blood pressure and dermal sensitivity effects of Nylon hollow fiber releasing Glycerin Trinitrate in vivo "

    Directory of Open Access Journals (Sweden)

    "Ostad SN

    2002-09-01

    Full Text Available In order to improve patient's compliance in taking glycerine trinitrate (GTN nylon hollow fiber which has been successfully used for release of chlorhexidine diacetate and levonorgestrel was employed to make nylon hollow fiber releasing GTN. Hollow nylon fibres of external diameter 0.63 mm, 75 mm long with an internal capacity of 16 μl, were filled with GTN (190 mg/ml in 70% ethanol (v/v or vehicle alone and the ends were heat-sealed. The fibers were then immersed in 10 ml of 0.9% (w/v saline in a separating funnel. The GTN release pattern from fiber, the effect of the product on blood pressure and its potential dermal toxicity were assessed. The release of GTN from the fibres was approximately 2.7 μg/min when the fibres contained 16 mg of drug. The results showed that the amount of GTN within the single fibre was enough to reduce blood pressure significantly, while it did not show significant dermal toxicity. It is concluded that GTN fiber, if used as monofilament, is not an alternative method for GTN delivery.

  14. Prednisolone reduces nitric oxide-induced migraine

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bikash Medhi

    2008-07-01

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

  16. Towards a reliable animal model of migraine

    DEFF Research Database (Denmark)

    Olesen, Jes; Jansen-Olesen, Inger

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg; Olesen, J

    1994-01-01

    The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric...... in the cascade of intracellular reactions triggered by NO. These novel observations change current views on vascular headache mechanisms and the importance of NO as an initiator of the migraine attacks dictates new approaches to the pharmacological treatment of migraine and other vascular headaches....

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

    Science.gov (United States)

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

    2009-09-01

    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). 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. 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. 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.

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

    DEFF Research Database (Denmark)

    Guo, Song; Ashina, Messoud; Olesen, Jes

    2013-01-01

    InvestigationSodium nitroprusside (SNP) is a powerful vasodilatory agent that, similarly to glyceryl trinitrate (GTN), releases nitric oxide (NO) but in contrast does not pass the blood-brain barrier. Nevertheless, it has already been used in animal models without any knowledge of its headache......-inducing potential. We hypothesized that SNP would induce headache and vasodilation of cephalic and radial but not cerebral arteries.MethodsFive healthy volunteers received intravenous infusions of SNP in a non-randomized dose-titration (1-5 µg/kg/min) study. We recorded headache intensity (verbal rating scale from...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    and in nine of 13 with placebo (p=0.68). The headache scores were similar after the two treatments (p=0.58). Thus CGRP receptor blockade did not prevent GTN-induced migraine. CONCLUSIONS: The present study indicates that NO does not induce migraine by liberating CGRP. The most likely explanation for our...

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

    Science.gov (United States)

    Schytz, Henrik W.; Hansen, Jakob M.; Phillip, Dorte; Selb, Juliette; Boas, David A.; Ashina, Messoud

    2013-01-01

    Background The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before. Objective To investigate changes in spontaneous low-frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near-infrared spectroscopy in FHM patients. Methods Twenty-three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 μg/kg/minute over 20 minutes. Using near-infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion. Results GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post-hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695). Conclusion FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM. PMID:22352839

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

    Science.gov (United States)

    Mollace, Vincenzo; Muscoli, Carolina; Dagostino, Concetta; Giancotti, Luigino Antonio; Gliozzi, Micaela; Sacco, Iolanda; Visalli, Valeria; Gratteri, Santo; Palma, Ernesto; Malara, Natalia; Musolino, Vincenzo; Carresi, Cristina; Muscoli, Saverio; Vitale, Cristiana; Salvemini, Daniela; Romeo, Francesco

    2014-11-01

    Bioconversion of glyceryl trinitrate (GTN) into nitric oxide (NO) by aldehyde dehydrogenase-2 (ALDH-2) is a crucial mechanism which drives vasodilatory and antiplatelet effect of organic nitrates in vitro and in vivo. Oxidative stress generated by overproduction of free radical species, mostly superoxide anions and NO-derived peroxynitrite, has been suggested to play a pivotal role in the development of nitrate tolerance, though the mechanism still remains unclear. Here we studied the free radical-dependent impairment of ALDH-2 in platelets as well as vascular tissues undergoing organic nitrate ester tolerance and potential benefit when using the selective peroxynitrite decomposition catalyst Mn(III) tetrakis (4-Benzoic acid) porphyrin (MnTBAP). Washed human platelets were made tolerant to nitrates via incubation with GTN for 4h. This was expressed by attenuation of platelet aggregation induced by thrombin (40U/mL), an effect accompanied by GTN-related induction of cGMP levels in platelets undergoing thrombin-induced aggregation. Both effects were associated to attenuated GTN-induced nitrite formation in platelets supernatants and to prominent nitration of ALDH-2, the GTN to NO metabolizing enzyme, suggesting that GTN tolerance was associated to reduced NO formation via impairment of ALDH-2. These effects were all antagonized by co-incubation of platelets with MnTBAP, which restored GTN-induced responses in tolerant platelets. Comparable effect was found under in in vivo settings. Indeed, MnTBAP (10mg/kg, i.p.) significantly restored the hypotensive effect of bolus injection of GTN in rats made tolerants to organic nitrates via chronic administration of isosorbide-5-mononitrate (IS-5-MN), thus confirming the role of peroxynitrite overproduction in the development of tolerance to vascular responses induced by organic nitrates. In conclusion, oxidative stress subsequent to prolonged use of organic nitrates, which occurs via nitration of ALDH-2, represents a key event

  3. Experimental study of faecal continence and colostomy irrigation.

    Science.gov (United States)

    O'Bichere, A; Sibbons, P; Doré, C; Green, C; Phillips, R K

    2000-07-01

    Colostomy irrigation is a useful method of achieving faecal continence in selected conditions, but remains largely underutilized because it is time consuming. This study investigated the effect of modifying irrigation technique (route, infusion regimen and pharmacological manipulation) on colonic emptying time in a porcine model. An end-colostomy and caecostomy were fashioned in six pigs. Twenty markers were introduced into the caecum immediately before colonic irrigation. Irrigation route (antegrade or retrograde), infusion regimen (tap water, polyethylene glycol (PEG), 1.5 per cent glycine) and pharmacological agent (glyceryl trinitrate (GTN) 0.25 mg/kg, diltiazem 3.9 mg/kg, bisacodyl 0.25 mg/kg) were assigned to each animal at random. Colonic transit was assessed by quantifying cumulative expelled markers (CEM) and stool every hour for 12 h. Mean CEM at 6 h for bisacodyl, GTN and diltiazem were 18.17, 12.17 and zero respectively; all pairwise differences in means were significant (P irrigation. PEG and glycine enhance emptying similar to bisacodyl and GTN solution. These findings show promise for improved faecal continence by colostomy irrigation and may justify construction of a Malone conduit at the time of colostomy in selected patients who wish to irrigate. Presented in part to the British Society of Gastroenterology in Glasgow, UK, March 1999, and published in abstract form as Gut 1999; 44(Suppl 1): A135

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

    International Nuclear Information System (INIS)

    Dahl, A.; Russell, D.; Nyberg-Hansen, R.; Rootwelt, K.

    1990-01-01

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

  5. Understanding organic nitrates – a vein hope?

    Science.gov (United States)

    Miller, Mark R; Wadsworth, Roger M

    2009-01-01

    The organic nitrate drugs, such as glyceryl trinitrate (GTN; nitroglycerin), are clinically effective in angina because of their dilator profile in veins and arteries. The exact mechanism of intracellular delivery of nitric oxide (NO), or another NO-containing species, from these compounds is not understood. However, mitochondrial aldehyde dehydrogenase (mtALDH) has recently been identified as an organic nitrate bioactivation enzyme. Nitrate tolerance, the loss of effect of organic nitrates over time, is caused by reduced bioactivation and/or generation of NO-scavenging oxygen-free radicals. In a recent issue of the British Journal of Pharmacology, Wenzl et al. show that guinea-pigs, deficient in ascorbate, also have impaired responsiveness to GTN, but nitrate tolerance was not due to ascorbate deficiency that exhibited divergent changes in mtALDH activity. Thus, the complex function of mtALDH appears to be the key to activation of GTN, the active NO species formed and the induction of tolerance that can limit clinical effectiveness of organic nitrate drugs. British Journal of Pharmacology (2009) 157, 565–567; doi:10.1111/j.1476-5381.2009.00193.x This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 The paper by Wenzl et al. is available from http://www3.interscience.wiley.com/cgi-bin/fulltext/122221718/PDFSTART PMID:19630835

  6. Efficacy of transdermal nitroglycerine in idiopathic pre-term labour.

    Science.gov (United States)

    Shaikh, Shahida; Shaikh, Abdul Hameed; Akhter, Saleem; Isran, Basma

    2012-01-01

    To determine the efficacy of transdermal Nitroglycerine patch in idiopathic pre-term labour and foetomaternal outcome. This quasi-experimental study was conducted at the Obstetrics Unit-II of Shaikh Zayed Hospital for Women, Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, from Jan 1 to June 30, 2010. Sixtyfive pregnant women at 28-34 weeks of gestation were recruited after they met the selection criteria based on non-probability consecutive sampling. Initially, 73 patients were selected, but 65 of them completed the treatment, while 8 patients refused to continue. Patients diagnosed with pre-term labour were given glyceryl trinitrate (GTN) 5 mg/12 hours transdermal patch which was applied on the anterior abdominal wall. The second patch of same dose was given after 12 hours. Arrest of labour, prolongation of pregnancy in days or weeks along with side effects of the agent were monitored. Patients were followed till delivery to know the foeto-maternal outcome. Dramatic effects were seen in around 60 (92.3%), of the total patients who had felt relief from premature labour pains within the first hour and only 5 (7.6%) patients could not go beyond 24 hours, as among them 3 (4.61%) had previous uterine scar and 2 (3.07%) developed ruptured membranes after 12 hours of admission and their babies also could not survive. Mean pregnancy prolongation was 15.35 +/- 9.45 days (min: 4 max: 35), so delivery was deferred up to 48 hours, 3 to 7 days and more than 7 days in 4 (6.15%), 6 (9.23%) and 50 (76.92%) respectively. Glyceryl trinitrate, trans dermal patch is effective and safe tocolytic in idiopathic preterm labour. By prolonging pregnancy it improves neonatal outcome.

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

    Science.gov (United States)

    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

  8. Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension.

    Science.gov (United States)

    Zizek, B; Poredos, P

    2001-02-01

    To evaluate whether endothelium-dependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between flow-mediated vasodilation (FMD) and hyperinsulinaemia/insulin resistance. Cross-sectional study. Angiology department at a teaching hospital. The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age-matched, normotensive volunteers as controls. We also investigated 41 normotonics with FT aged 20-30 (25) years and 41 age-and sex-matched controls without FT. Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. In hypertonics FMD was significantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P=0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was comparable in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). In treated patients with EH, flow-mediated dilation of the BA as well as endothelium-independent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications.

  9. 6D.03: FLOW-MEDIATED DILATATION (FMD) AND ENDOTHELIUM-INDEPENDENT DILATATION (EID) IN PATIENTS WITH MULTIFOCAL FIBROMUSCULAR DYSPLASIA: A CROSS-SECTIONAL STUDY.

    Science.gov (United States)

    Khettab, H; Lorthior, A; Niarra, R; Chambon, Y; Jeunemaitre, X; Plouin, P F; Laurent, S; Boutouyrie, P; Azizi, M

    2015-06-01

    Fibromuscular dysplasia (FD) is a rare idiopathic, segmental, non-atherosclerotic non-inflammatory vascular disease. We previously showed that FD is a general arterial disease with focal exacerbation of the trait. However, whether endothelial dysfunction may be involved in the pathophysiology of FD is unclear. In a cross sectional study, we compared the endothelial function between 50 patients with multifocal FD of renal/carotid arteries confirmed by CT-angiography, 50 essential hypertensive (EH) patients matched for age, sex, ethnicity and BP and 50 healthy subjects (HS) matched for age, sex and ethnicity. Exclusion criteria were: tobacco consumption, hypercholesterolemia, diabetes, aspirin or statin treatment. Brachial artery (BA) FMD after release of hand ischemia and glyceryl trinitrate (GTN)-induced EID was measured using a high-resolution radiofrequency-based echotracking system blind to the diagnosis. FD, EH and HS were well matched (52yrs, 85% women, 80% caucasian). SBP was higher in FD (125 ± 15mmHg) and EH (121 ± 12mmHg) than EH (113 ± 10mmHg) despite antihypertensive treatments. BA external diameter was significantly lower in FD than in both HS and EH before, during and after hand ischemia and after GTN. BA intima media thickness (IMT), internal diameter did not differ between the 3 groups. FMD (%) or EID (%) did not significantly differ between the 3 groups. BA flow velocity did not significantly differ in any experimental condition.(Figure is included in full-text article.) : In conclusion, despite showing similar acute vasodilatory responses to flow and GTN, FD patients differed from EH and HS in terms of arterial morphology with smaller BA diameter associated with similar IMT. This paradoxical remodeling may suggest a chronic defect in the endothelium-dependent pathways involved in arterial remodeling in FD patients.

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

    Science.gov (United States)

    2010-04-01

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

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

    Directory of Open Access Journals (Sweden)

    J. Sedef Göçmen

    2012-12-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mužíková Jitka

    2015-03-01

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

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

    Science.gov (United States)

    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.

  15. The role of therapeutic optimism in recruitment to a clinical trial in a peripartum setting: balancing hope and uncertainty.

    Science.gov (United States)

    Hallowell, Nina; Snowdon, Claire; Morrow, Susan; Norman, Jane E; Denison, Fiona C; Lawton, Julia

    2016-06-01

    Hope has therapeutic value because it enables people to cope with uncertainty about their future health. Indeed, hope, or therapeutic optimism (TO), is seen as an essential aspect of the provision and experience of medical care. The role of TO in clinical research has been briefly discussed, but the concept, and whether it can be transferred from care to research and from patients to clinicians, has not been fully investigated. The role played by TO in research emerged during interviews with staff involved in a peripartum trial. This paper unpacks the concept of TO in this setting and considers the role it may play in the wider delivery of clinical trials. The Got-it trial is a UK-based, randomised placebo-controlled trial that investigates the use of sublingual glyceryl trinitrate (GTN) spray to treat retained placenta. Qualitative data were collected in open-ended interviews with obstetricians, research and clinical midwives (n =27) involved in trial recruitment. Data were analysed using the method of constant comparison. TO influenced staff engagement with Got-it at different points in the trial and in different ways. Prior knowledge of, and familiarity with, GTN meant that from the outset staff perceived the trial as low risk. TO facilitated staff involvement in the trial; staff who already understood GTN's effects were optimistic that it would work, and staff collaborated because they hoped that the trial would address what they identified as an important clinical need. TO could fluctuate over the course of the trial, and was sustained or undermined by unofficial observation of clinical outcomes and speculations about treatment allocation. Thus, TO appeared to be influenced by key situational factors: prior knowledge and experience, clinical need and observed participant outcomes. Situational TO plays a role in facilitating staff engagement with clinical research. TO may affect trial recruitment by enabling staff to sustain the levels of uncertainty, or

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

    Science.gov (United States)

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

    2013-04-01

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

  17. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

    Science.gov (United States)

    Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-05

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

  19. Investigation of paramedics' compliance with clinical practice guidelines for the management of chest pain.

    LENUS (Irish Health Repository)

    Figgis, Ken

    2012-01-31

    BACKGROUND: Acute coronary syndromes remain a leading cause of preventable early deaths. However, previous studies have indicated that paramedics\\' compliance with chest pain protocols is suboptimal and that many patients do not receive the benefits of appropriate prehospital treatment. AIMS: To evaluate paramedics\\' level of compliance with national clinical practice guidelines and to investigate why, in certain circumstances, they may deviate from the clinical guidelines. SETTING: The Health Service Executive Mid-Western Regional Ambulance Service which serves a mixed urban and rural population across three counties in the west of Ireland. METHOD: A retrospective review of completed ambulance Patient Care Report Forms was conducted for all adult patients with non-traumatic chest pain treated between 1 December 2007 and 31 March 2008. During the same study period, paramedics were asked to complete a prospective questionnaire survey investigating the rationale behind their treatment decisions, their estimation of patient risk and their attitudes towards the clinical practice guidelines and training. RESULTS: 382 completed Patient Care Report Forms were identified for patients with chest pain, of whom 84.8% received ECG monitoring, 75.9% were given oxygen, 44.8% were treated with sublingual glyceryl trinitrate (GTN) and 50.8% were treated with aspirin. Only 20.4% of patients had a prehospital 12-lead ECG recorded. 58 completed questionnaires were returned (response rate 15%); 64% of respondents said they had received insufficient training to identify ECG abnormalities. CONCLUSIONS: Prehospital treatment with oxygen, aspirin, sublingual GTN and ECG monitoring remains underused by paramedics, even though only a small number of patients had documented contraindications to their use. The small number of patients who received a prehospital 12-lead ECG is a cause of particular concern and suggests that incomplete patient assessment may contribute to undertreatment

  20. Oxidation of tertiary homoallylic alcohols by thallium trinitrate: fragmentation versus ring contraction

    International Nuclear Information System (INIS)

    Silva Junior, Luiz F.; Quintiliano, Samir A.P.; Ferraz, Helena M.C.; Santos, Leonardo S.; Eberlin, Marcos N.

    2006-01-01

    The oxidation of tertiary homoallylic alcohols with thallium trinitrate (TTN) was investigated. The alcohols bearing an allylic methyl group lose a molecule of acetone via a fragmentation reaction that leads to isomeric secondary allylic alcohols as major products, together with their corresponding acetylated derivatives. On the other hand, treating analogous tertiary alcohols without the allylic methyl group with TTN gives indans, through a ring contraction reaction. (author)

  1. The reaction of 1-tetralones with thallium trinitrate supported on clay: ring contraction vs a-oxidation

    Directory of Open Access Journals (Sweden)

    Ferraz Helena M. C.

    2001-01-01

    Full Text Available The reaction of a series of 1-tetralones with thallium trinitrate supported on Montmorillonite K-10 clay led to products of ring contraction (methyl indan-1-carboxylates and/or alpha-oxidation (2-methoxy-1-tetralones, in variable yields.

  2. Towards the damage evaluation using Gurson-Tvergaard-Needleman (GTN) model for hot forming processes

    Science.gov (United States)

    Imran, Muhammad; Bambach, Markus

    2018-05-01

    In the production of semi-finished metal products, hot forming is used to eliminate the pores and voids from the casting process under compressive stresses and to modify the microstructure for further processing. In the case of caliber and flat rolling processes, tensile stresses occur at certain roll gap ratios which promote pore formation on nonmetallic inclusion. The formation of new pores contributes to ductile damage and reduces the load carrying capacity of the material. In the literature, the damage nucleation and growth during the hot forming process are not comprehensively described. The aim of this study is to understand the damage initiation and growth mechanism during hot forming processes. Hot tensile tests are performed at different temperatures and strain rates for 16MnCrS5 steel. To investigate the influence of geometrical variations on the damage mechanism, specimens with different stress triaxiality ratios are used. Finite element simulations using the Gurson-Tvergaard-Needleman (GTN) damage model are performed to estimate the critical void fraction for the damage initiation and the evolution of the void volume fraction. The results showed that the GTN model underestimates the softening of the material due to the independence of the temperature and the strain rate.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics...... of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms....

  4. Impaired vascular function in physically active premenopausal women with functional hypothalamic amenorrhea is associated with low shear stress and increased vascular tone.

    Science.gov (United States)

    O'Donnell, Emma; Goodman, Jack M; Mak, Susanna; Harvey, Paula J

    2014-05-01

    Exercise-trained hypoestrogenic premenopausal women with functional hypothalamic amenorrhea (ExFHA) exhibit impaired endothelial function. The vascular effects of an acute bout of exercise, a potent nitric oxide stimulus, in these women are unknown. Three groups were studied: recreationally active ExFHA women (n = 12; 24.2 ± 1.2 years of age; mean ± SEM), and recreationally active (ExOv; n = 14; 23.5 ± 1.2 years of age) and sedentary (SedOv; n = 15; 23.1 ± 0.5 years of age) ovulatory eumenorrheic women. Calf blood flow (CBF) and brachial artery flow-mediated dilation (FMD) were evaluated using plethysmographic and ultrasound techniques, respectively, both before and 1 hour after 45 minutes of moderate-intensity exercise. Endothelium-independent dilation was assessed at baseline using glyceryl trinitrate. Calf vascular resistance (CVR) and brachial peak shear rate, as determined by the area under the curve (SRAUCpk), were also calculated. FMD and glyceryl trinitrate responses were lower (P .05) the findings. CBF was lower (P .05) between the groups. CBF in ExFHA was increased (P < .05) and CVR decreased (P < .05) to levels observed in ovulatory women. Acute dynamic exercise improves vascular function in ExFHA women. Although the role of estrogen deficiency per se is unclear, our findings suggest that low shear rate and increased vasoconstrictor tone may play a role in impaired basal vascular function in these women.

  5. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND AND AIM: Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-rela...

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

    African Journals Online (AJOL)

    cein, water saturated butanol (900 µl) was added followed by vortexing and centrifugation at .... The crystal structure of P. aeruginosa LasR ligand bind- ing domain was retrieved from Protein Data Bank (PDB. ID: 2UV0)22 and the rhlr receptor ...

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    Nitric oxide (NO) may play a key role in migraine and other vascular headaches since glyceryl trinitrate (a donor of NO) and histamine (which probably activates endothelial NO formation) both cause a pulsating dose-dependent headache with several migrainous characteristics. At relatively high doses...... Olesen, Lars Thomsen and Helle Iversen suggest that migraine may be caused by increased amounts and/or affinity of an enzyme in the NO-triggered cascade of reactions. NO may also be involved in the pathogenesis of other vascular headaches....

  8. Oxidation reactions of derivatives of cis-octalins promoted by thallium trinitrate (TTN)

    International Nuclear Information System (INIS)

    Ferraz, Helena M.C.; Carneiro, Vania M.T.; Vieira, Tiago O.; Silva Junior, Luiz F.

    2008-01-01

    The reaction of ten cis-octalins and cis-octalones with thallium trinitrate (TTN) leads to different products, depending mainly on the substitution pattern of the substrate. Functionalized cis-hydrindanes were obtained from the reaction of 1,2,3,4,4a,5,8,8a-octahydro- 4a-methylnaphthalene and of 1,2,3,4,4a,5,8,8a-octahydro-4a,7-dimethylnaphthalene with TTN in acetonitrile, whereas a cyclic ether was formed treating 1,2,3,4,4a,5,8,8a-octahydro-6,8a-dimethylnaphthalene-1-ol with TTN in trimethylorthoformate (TMOF). (author)

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs......·91-1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90-1·22; p=0·55). INTERPRETATION: In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show...

  10. Rearrangement of beta,gamma-unsaturated esters with thallium trinitrate: synthesis of indans bearing a beta-keto ester moiety

    Directory of Open Access Journals (Sweden)

    Silva Jr. Luiz F.

    2006-01-01

    Full Text Available The rearrangement of beta,gamma-unsaturated esters, such as 2-(3,4-dihydronaphthalen-1-yl-propionic acid ethyl ester, with thallium trinitrate (TTN in acetic acid leads to 3-indan-1-yl-2-methyl-3-oxo-propionic acid ethyl ester in good yield, through a ring contraction reaction. The new indans thus obtained feature a beta-keto ester moiety, which would be useful for further functionalization.

  11. Immobilization of L-glyceryl phosphorylcholine: isolation of phosphorylcholine-binding proteins from seminal plasma

    Czech Academy of Sciences Publication Activity Database

    Liberda, J.; Maňásková, Pavla; Švesták, M.; Jonáková, Věra; Tichá, M.

    2002-01-01

    Roč. 770, 1-2 (2002), s. 101-110 ISSN 0378-4347 R&D Projects: GA ČR GA303/99/0357; GA ČR GV524/96/K162 Institutional research plan: CEZ:AV0Z5052915; CEZ:MSM 113100001 Keywords : L-glyceryl phosphorylcholine * proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.913, year: 2002

  12. Fluid regimens for colostomy irrigation: a systematic review.

    Science.gov (United States)

    Lizarondo, Lucylynn; Aye Gyi, Aye; Schultz, Tim

    2008-09-01

    Background  Various techniques for managing faecal evacuation have been proposed; however, colostomy irrigation is favoured as it leads to better patient outcomes. Alternative fluid regimens for colostomy irrigation have been suggested to achieve effective evacuation. Aim  The objective of this review was to summarise the best available evidence on the most effective fluid regimen for colostomy irrigation. Search strategy  Trials were identified by electronic searches of CINAHL, PubMed, MEDLINE, Current Contents, the Cochrane Library and EMBASE. Unpublished articles and references lists from included studies were also searched. Selection criteria  Randomised controlled trials and before-and-after studies investigating any fluid regimen for colostomy irrigation were eligible for inclusion. Outcomes measured included fluid inflow time, total wash-out time, haemodynamic changes during irrigation, cramps, leakage episodes, quality of life and level of satisfaction. Data collection and analysis  Trial selection, quality appraisal and data extraction were carried out independently by two reviewers. Differences in opinion were resolved by discussion. Main results  The systematic literature search strategy identified two cross-over trials that compared water with another fluid regimen. Owing to the differences in irrigating solutions used, the results were not pooled for analysis. Both the polyethylene glycol electrolyte solution and glyceryl trinitrate performed significantly better than water. Conclusion  There is some evidence to support the effectiveness of fluid regimens other than water, such as polyethylene glycol electrolyte and glyceryl trinitrate, for colostomy irrigation. Further well-designed clinical trials are required to establish solid evidence on the effectiveness of other irrigating solutions that might enhance colonic irrigation. © 2008 The Authors. Journal Compilation © Blackwell Publishing Asia Pty Ltd.

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

    Directory of Open Access Journals (Sweden)

    Geovana R. Cosenza

    2014-03-01

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

  14. Arterial alterations in severely obese children with obstructive sleep apnoea.

    Science.gov (United States)

    Dubern, Beatrice; Aggoun, Yacine; Boulé, Michèle; Fauroux, Brigitte; Bonnet, Damien; Tounian, Patrick

    2010-05-03

    Obstructive sleep apnoea (OSA) in obese adults is associated with cardiovascular disease independently of obesity. Vascular alterations exist in children with obesity and may constitute the first stage in the development of adulthood cardiovascular disease. To investigate the relationship between OSA and early arterial alterations in obese children. Cross-sectional study of a prospective cohort. A total of 51 children with severe obesity managed at a teaching hospital outpatient clinic. Polysomnography was performed. We measured the intima-media thickness and incremental elastic modulus (Einc) to assess the mechanical characteristics of the common carotid artery. Arterial endothelial function was evaluated by measuring flow-mediated dilation and glyceryl trinitrate-mediated dilation (GTNMD) of the brachial artery. A total of 24 (47%) children had a desaturation index (DI) >10/h and 7 (14%) had a respiratory event index >10/h. DI >10/h was associated with significantly higher values of Einc (4.0 + or - 0.5 vs. 2.4 + or - 0.4 mm Hg(-1) x 10(3), p=0.003) and GTNMD (18.0 + or - 1.1 vs. 14.1 + or - 1.0 %, p=0.02) after adjustment for age, sex, body mass index, fasting insulin, and leptin. In the univariate analysis, GTNMD correlated positively with DI (r=0.14, p=0.02) after adjustment for age, sex, fasting insulin and leptin. By multivariate analysis with BMI as an additional independent variable, both GTNMD and Einc correlated significantly with DI (beta=0.4, p=0.02 and beta=0.27, p=0.04, respectively). OSA in children is associated with arterial alterations independently from obesity. The increased vasodilation in response to glyceryl trinitrate reflects pre-existing vasoconstriction probably induced by intermittent hypoxia. OSA should be detected early in children with severe obesity.

  15. Chitosan and Glyceryl Monooleate Nanostructures Containing Gemcitabine: Potential Delivery System for Pancreatic Cancer Treatment

    OpenAIRE

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

    2010-01-01

    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 cytot...

  16. Thallium trinitrate-mediated ring contraction of 1,2-dihydronaphthalenes: the effect of electron-donating and electron-withdrawing groups

    International Nuclear Information System (INIS)

    Silva Junior, Luiz F.; Sousa, Raquel M.F.; Ferraz, Helena M.C.; Aguilar, Andrea M.

    2005-01-01

    The oxidation of a series of 1,2-dihydronaphthalenes substituted in the aromatic ring was investigated with thallium trinitrate (TTN) in methanol or in trimethylorthoformate (TMOF) as solvent. In all cases, indans are produced, although the yield varied from excellent to poor, depending on the structure of the substrate. The presence of an electron-donating group in the substrate favors the rearrangement, whereas significant amounts of glycolic derivatives, as well as naphthalenes, were obtained in the oxidation of 1,2-dihydronaphthalenes bearing electron-withdrawing groups, such as Br and NO 2 . Mechanisms for the formation of each of these products are proposed. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yongbin; Cha, Wan-gi; Kim, Naksoo [Department of Mechanical Engineering, Sogang University, 1 Sinsu-dong, Mapo-gu, Seoul, 121-742 (Korea, Republic of); Ko, Sangjin [Mold/die and forming technology team, Product prestige research lab, LG electronics, 222, LG-ro, Jinwi-myeon, Pyeongtaek-si, Gyeonggi-do, 451-713 (Korea, Republic of)

    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.

  19. Calcitonin gene-related peptide antagonism and cluster headache

    DEFF Research Database (Denmark)

    Ashina, Håkan; Newman, Lawrence; Ashina, Sait

    2017-01-01

    Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact...... role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide......" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play...

  20. Oxidation reactions of derivatives of cis-octalins promoted by thallium trinitrate (TTN); Reacoes de oxidacao de cis-octalinas promovidas por trinitrato de talio (TTN)

    Energy Technology Data Exchange (ETDEWEB)

    Ferraz, Helena M.C.; Carneiro, Vania M.T.; Vieira, Tiago O.; Silva Junior, Luiz F. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica]. E-mail: luizfsjr@iq.usp.br

    2008-07-01

    The reaction of ten cis-octalins and cis-octalones with thallium trinitrate (TTN) leads to different products, depending mainly on the substitution pattern of the substrate. Functionalized cis-hydrindanes were obtained from the reaction of 1,2,3,4,4a,5,8,8a-octahydro- 4a-methylnaphthalene and of 1,2,3,4,4a,5,8,8a-octahydro-4a,7-dimethylnaphthalene with TTN in acetonitrile, whereas a cyclic ether was formed treating 1,2,3,4,4a,5,8,8a-octahydro-6,8a-dimethylnaphthalene-1-ol with TTN in trimethylorthoformate (TMOF). (author)

  1. The role of nitrates in the prevention of preeclampsia: an update.

    Science.gov (United States)

    Kalidindi, Madhavi; Velauthar, Luxmi; Khan, Khalid; Aquilina, Joseph

    2012-12-01

    Defective nitric oxide synthesis and nitric oxide-mediated vasodilatation is widely documented in the pathophysiology of preeclampsia, a leading cause of maternal and perinatal morbidity and mortality worldwide. Several studies demonstrated the beneficial role of nitric oxide agents, especially glyceryl trinitrate and L-arginine in reducing the blood pressure and improving the uteroplacental blood flow velocities. However, there is insufficient evidence on the efficacy and safety of these agents in the prevention of preeclampsia and its complications, as there are very few randomized controlled trials with small number of women. The aim of this review is to summarize and evaluate the role of nitrates in the prevention of preeclampsia based on the available evidence in the literature till date and suggestions for future research. Supplementation with L-arginine and antioxidant vitamins reduced the incidence of preeclampsia in women at high risk of preeclampsia [P nitrates are needed in high-risk women to validate these findings.

  2. Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

    DEFF Research Database (Denmark)

    Thomsen, L L; Iversen, Helle Klingenberg; Emmeluth, C

    1995-01-01

    before and immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or placebo (isotonic saline) was infused successively...... for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats. min-1. No changes in endothelin-1 plasma...... levels were induced by NTG infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion....

  3. Green enzymatic production of glyceryl monoundecylenate using immobilized Candida antarctica lipase B.

    Science.gov (United States)

    Yadav, Manish G; Kavadia, Monali R; Vadgama, Rajeshkumar N; Odaneth, Annamma A; Lali, Arvind M

    2017-11-26

    Enzymatic synthesis of glyceryl monoundecylenate (GMU) was performed using indigenously immobilized Candida anatarctica lipase B preparation (named as PyCal) using glycerol and undecylenic acid as substrates. The effect of molar ratio, enzyme load, reaction time, and organic solvent on the reaction conversion was determined. Both batch and continuous processes for GMU synthesis with shortened reaction time were developed. Under optimized batch reaction conditions such as 1:5 molar ratio of undecylenic acid and glycerol, 2 h of reaction time at 30% substrate concentration in tert-butyl alcohol, conversion of 82% in the absence of molecular sieve, and conversion of 93% in the presence of molecular sieve were achieved. Packed bed reactor studies resulted in high conversion of 86% in 10-min residence time. Characterization of formed GMU was performed by FTIR, MS/MS. Enzymatic process resulted in GMU as a predominant product in high yield and shorter reaction time periods with GMU content of 92% and DAG content of 8%. Optimized GMU synthesis in the present study can be used as a useful reference for industrial synthesis of fatty acid esters of glycerol by the enzymatic route.

  4. Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN).

    Science.gov (United States)

    Reddy, Gunda; Song, Jian; Kirby, Paul; Johnson, Mark S

    2011-12-24

    Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic toxicity of these compounds was evaluated to predict the potential adverse human health effects from exposure by using a standard genetic toxicity test battery which included: a gene mutation test in bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome aberration test and an in vivo mouse micronucleus test. The results of the Ames test showed that EDDN increased the mean number of revertants per plate with strain TA100, without activation, at 5000μg/plate compared to the solvent control, which indicated a positive result. No positive results were observed with the other tester strains with or without activation in Salmonella typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA. DETN was negative for all Salmonella tester strains and E. coli up to 5000μg/plate both with and without metabolic activation. The CHO cell chromosome aberration assay was performed using EDDN and DETN at concentrations up to 5000μg/mL. The results indicate that these compounds did not induce structural chromosomal aberrations at all tested concentrations in CHO cells, with or without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1 mouse at doses up to 2000mg/kg, did not induce any significant increase in the number of micronuclei in bone marrow erythrocytes. These studies demonstrate that EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other strains, for in vitro induction of chromosomal aberrations in CHO cells, and for micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in all in vitro and in vivo tests. These results show the in

  5. Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

    DEFF Research Database (Denmark)

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

    2018-01-01

    in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus...... glycerytrinitrate infusion ( P ... after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level....

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

    Directory of Open Access Journals (Sweden)

    Jie Lai

    2009-12-01

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

  7. Evaluation of the effects of chronic biomass fuel smoke exposure on peripheral endothelial functions: an observational study.

    Science.gov (United States)

    Buturak, Ali; Genç, Ahmet; Ulus, Ozden Sıla; Duygu, Egemen; Okmen, Arda Sanlı; Uyarel, Hüseyin

    2011-09-01

    To evaluate the effect of chronic biomass fuel (BMF) smoke exposure on peripheral endothelial functions. Forty-seven healthy subjects who have been exposed to BMF smoke since birth (mean age 31.6±6.8 years, 21 male) were enrolled in the present cross-sectional observational study. The control group consisted of 32 healthy subjects (mean age 27.9±4.4 years, 11 male). The carotid intima media thickness (CIMT), flow associated dilatation (FAD %) and endothelium independent vasodilatation (GTN %) were assessed in all subjects. The carotid CIMT was defined as the distance between the leading edge of the lumen-intima and the media-adventitia interfaces. FAD % was defined as the percentage change in the internal diameter of the brachial artery during reactive hyperemia related to the baseline. GTN % was defined as the change in diameter in response to the application of 400 µg of glyceril trinitrate relative to the baseline scan at the end of the fourth minute. Statistical analysis was performed using Student's t-test, Chi-square test and Spearman rank order correlation analysis. The average exposure time of the subjects to biomass fuel smoke was 31.7±6.6 years. They have been exposed to dung inhalation products meanly 8.3±1.8 months in a year seasonally. The average daily exposure time was 15.7±3.3 hours. CIMT values of the two groups were not statistically different from each other (0.47±0.09 vs. 0.49±0.06 mm, p=0.138). However, a markedly reduced FAD % was determined in the study group (5.06±4.95 vs. 10.7±4.64, pinhalation products. Therefore, chronic BMF smoke exposure may be a risk factor for the development of endothelial dysfunction.

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

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Hornum, Mads; Elkjaer, Margarita

    2009-01-01

    OBJECTIVE: Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP...... (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS: Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared...... (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS: The trial showed...

  9. Evidence-Based Management of Pain After Excisional Haemorrhoidectomy Surgery: A PROSPECT Review Update.

    Science.gov (United States)

    Sammour, Tarik; Barazanchi, Ahmed W H; Hill, Andrew G

    2017-02-01

    The aim of this systematic review was to update previous PROSPECT ( http://www.postoppain.org ) review recommendations for the management of pain after excisional haemorrhoidectomy. Randomized studies and reviews published in the English language from July 2006 (end date of last review) to March 2016, assessing analgesic, anaesthetic, and operative interventions pertaining to excisional haemorrhoidectomy in adults, and reporting pain scores, were retrieved from the EMBASE and MEDLINE databases. An additional 464 studies were identified of which 74 met the inclusion criteria. There were 48 randomized controlled trials and 26 reviews. Quantitative analyses were not performed, as there were limited numbers of trials with a sufficiently homogeneous design. Pudendal nerve block, with or without general anaesthesia, is recommended for all patients undergoing haemorrhoidal surgery. Either closed haemorrhoidectomy, or open haemorrhoidectomy with electrocoagulation of the pedicle is recommended as the primary procedure. Combinations of analgesics (paracetamol, non-steroidal anti-inflammatory drugs, and opioids), topical lignocaine and glyceryl trinitrate, laxatives, and oral metronidazole are recommended post-operatively. The recommendations are largely based on single intervention, not multimodal intervention, studies.

  10. Patellar Tendinopathy.

    Science.gov (United States)

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

    2015-01-01

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

  11. Uso de inotropos y vasodilatadores en la comunicación interventricular

    Directory of Open Access Journals (Sweden)

    Lincoln de la Parte Pérez

    1996-04-01

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Sánchez, R.

    2011-09-01

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

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

  14. Site-specific immunosuppression using a new formulation of topical cyclosporine A with polyethylene glycol-8 glyceryl caprylate/caprate.

    Science.gov (United States)

    Tran, H S; Malli, D; Chrzanowski, F A; Puc, M M; Matthews, M S; Hewitt, C W

    1999-05-15

    Dermal application of immunosuppressants can be an effective means of achieving site-specific immunosuppression (SITE) on skin allografts in burn wound management and in the treatment of various immune skin disorders. We have previously reported success with topical cyclosporine A (tCsA) in the treatment of skin allograft rejection in rats. Using a new tCsA formulation with a penetration enhancer (PE), polyethylene glycol-8 (PEG-8) glyceryl caprylate/caprate (Labrasol, Gattefossé, St. Priest, France), in a trinary drug delivery system, we hypothesized that we would induce SITE and significantly delay rejection of dual skin allografts in rats. Dual rat skin allografts from Lewis x Brown-Norway (LBN) donors were grafted to Lewis (Lew) recipients. Experimental animals (EXP, n = 7) received a 10-day course of systemic cyclosporine (sCsA, 8 mg/kg/day) followed by topical application. One of the two allografts on each experimental animal received tCsA/PE application (5 mg/kg/day) until sacrifice (tCsA/PE-treated). The other allograft received vehicle only (vehicle-treated). Allogeneic controls (ALLO-CON, n = 9) received no sCsA or tCsA. First signs of rejection were determined based on the initial observation of erythema, hair loss, flakiness, and/or scabs. The mean time to rejection for ALLO-CON allografts was 6.3 +/- 0.7 days (t test, P = 0.0013); for vehicle-treated allografts, 12.3 +/- 3.8 days (paired t test, P = 0.0146); and for tCsA/PE-treated allografts, 25.6 +/- 5.4 days. The disparity of days to rejection between dual allografts in the ALLO-CON group was 0.0 +/- 0.0 day and that between the tCsA/PE- and vehicle-treated dual allografts was 13.3 +/- 3.9 days (t test, P = 0.0016). A new formulation of tCsA in a trinary drug delivery system is successful at delaying the onset of rejection in dual skin allografts in rats by SITE, and PEG-8 glyceryl caprylate/caprate may represent a potentially effective transdermal penetration enhancer. Copyright 1999 Academic

  15. Effects of glyceryl glucoside on AQP3 expression, barrier function and hydration of human skin.

    Science.gov (United States)

    Schrader, A; Siefken, W; Kueper, T; Breitenbach, U; Gatermann, C; Sperling, G; Biernoth, T; Scherner, C; Stäb, F; Wenck, H; Wittern, K-P; Blatt, T

    2012-01-01

    Aquaporins (AQPs) present in the epidermis are essential hydration-regulating elements controlling cellular water and glycerol transport. In this study, the potential of glyceryl glucoside [GG; alpha-D-glucopyranosyl-alpha-(1->2)-glycerol], an enhanced glycerol derivative, to increase the expression of AQP3 in vitro and ex vivo was evaluated. In vitro studies with real-time RT-PCR and FACS measurements were performed to test the induction by GG (3% w/v) of AQP3 mRNA and protein in cultured human keratinocytes. GG-containing formulations were applied topically to volunteer subjects and suction blister biopsies were analyzed to assess whether GG (5%) could penetrate the epidermis of intact skin, and subsequently upregulate AQP3 mRNA expression and improve barrier function. AQP3 mRNA and protein levels were significantly increased in cultured human keratinocytes. In the studies on volunteer subjects, GG significantly increased AQP3 mRNA levels in the skin and reduced transepidermal water loss compared with vehicle-controlled areas. GG promotes AQP3 mRNA and protein upregulation and improves skin barrier function, and may thus offer an effective treatment option for dehydrated skin. Copyright © 2012 S. Karger AG, Basel.

  16. Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.

    Science.gov (United States)

    Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo

    2005-10-01

    Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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.

  18. Lyotropic Liquid Crystalline Nanoparticles of Amphotericin B: Implication of Phytantriol and Glyceryl Monooleate on Bioavailability Enhancement.

    Science.gov (United States)

    Jain, Sanyog; Yadav, Pooja; Swami, Rajan; Swarnakar, Nitin Kumar; Kushwah, Varun; Katiyar, Sameer S

    2018-05-01

    Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (< 210 nm) with a narrow distribution (~ 0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity. PLCNPs presented slower release, i.e., ~ 80% as compared to ~ 90% release in case of GLCNPs after 120 h. Significantly higher uptake in Caco-2 monolayer substantiated the role of LCNPs in increasing the intestinal permeability followed by increased drug titer in plasma. Pharmacokinetic studies demonstrated potential of PT in enhancing the bioavailability (approximately sixfold) w.r.t. of its native counterpart with reduced nephrotoxicity as presented by reduced nephrotoxicity biomarkers and histology studies. These studies established usefulness of PLCNPs over GLCNPs and plain drug. It can be concluded that acid-resistant lipid, PT, can be utilized efficiently as an alternate lipid for the preparation of LCNPs to enhance bioavailability and to reduce nephrotoxicity of the drug as compared to other frequently used lipid, i.e., GMO.

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

    Science.gov (United States)

    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.

  20. Human chorionic gonadotrophin regression rate as a predictive factor of postmolar gestational trophoblastic neoplasm in high-risk hydatidiform mole: a case-control study.

    Science.gov (United States)

    Kim, Bo Wook; Cho, Hanbyoul; Kim, Hyunki; Nam, Eun Ji; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Kim, Jae-Hoon

    2012-01-01

    The aim of this study was early prediction of postmolar gestational trophoblastic neoplasm (GTN) after evacuation of high-risk mole, by comparison of human chorionic gonadotrophin (hCG) regression rates. Fifty patients with a high-risk mole initially and spontaneously regressing after molar evacuation were selected from January 1, 1996 to May 31, 2010 (spontaneous regression group). Fifty patients with a high-risk mole initially and progressing to postmolar GTN after molar evacuation were selected (postmolar GTN group). hCG regression rates represented as hCG/initial hCG were compared between the two groups. The sensitivity and specificity of these rates for prediction of postmolar GTN were assessed using receiver operating characteristic curves. Multivariate analyses of associations between risk factors and postmolar GTN progression were performed. The mean regression rate of hCG between the two groups was compared. hCG regression rates represented as hCG/initial hCG (%) were 0.36% in the spontaneous regression group and 1.45% in the postmolar GTN group in the second week (p=0.003). Prediction of postmolar GTN by hCG regression rate revealed a sensitivity of 48.0% and specificity of 89.5% with a cut-off value of 0.716% and area under the curve (AUC) of 0.759 in the 2nd week (pfactor for postmolar GTN. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

    Energy Technology Data Exchange (ETDEWEB)

    Vendramini-Costa, Débora Barbosa, E-mail: vendramini.debora@gmail.com [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Alcaide, Antonio [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Pelizzaro-Rocha, Karin Juliane [Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, SP (Brazil); Talero, Elena; Ávila-Román, Javier [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Garcia-Mauriño, Sofia [Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Seville (Spain); Pilli, Ronaldo Aloise [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Carvalho, João Ernesto de [Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP (Brazil); Motilva, Virginia [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain)

    2016-06-01

    Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1 expression

  2. Quality of life of gestational trophoblastic neoplasia survivors: a study of patients at the Philippine General Hospital trophoblastic disease section.

    Science.gov (United States)

    Cagayan, M Stephanie Fay S; Llarena, Raquel T

    2010-01-01

    To evaluate the quality of life (QOL) of patients who were diagnosed with gestational trophoblastic neoplasia (GTN) at the Philippine General Hospital Trophoblastic Disease Section and who were in remission at the time of this study. A cross-sectional descriptive study designed to measure the QOL of all patients diagnosed as having GTN in remission and following up at the Philippine General Hospital Trophoblastic Disease Outpatient Clinic from May-August 2008 (N = 46). This study used the short form 12-question (SF-12) survey forms to evaluate the QOL of patients diagnosed with GTN. Scores from the SF-12 were analyzed using Pearson's correlation. Statistical significance was assumed for p values educational level and physical functioning. A negative correlation was found between the stage of GTN and patients' general health. In conclusion, the survivors' age, educational level and type of treatment had impact on the QOL among GTN survivors in terms of physical functioning. No relationship was established between the demographic variables and mental status. SF-12 appears to be a reliable instrument, suggesting its potential in measuring health status in GTN survivors. Age, educational attainment and type of treatment were shown to have an impact on the QOL of the surviving GTN patients.

  3. Effects of 6 weeks oral administration of Phyllanthus acidus leaf water extract on the vascular functions of middle-aged male rats.

    Science.gov (United States)

    Chongsa, Watchara; Kanokwiroon, Kanyanatt; Jansakul, Chaweewan

    2015-12-24

    . Relaxation of the Phe-precontracted thoracic aortic ring to acetylcholine, but not to glyceryl trinitrate, was higher for the PA-treated than for the control aortic rings and this effect was abolished by l-NA. The mesenteric rings of the PA treated group showed a lower sensitivity on the contractile response to Phe than that of the control group, and this effect was abolished by l-NA. Vasodilatation to acetylcholine, but not to glyceryl trinitrate, of the PA treated-mesenteric ring was more sensitive than that of the control group and this effect was abolished by l-NA. The expression of eNOS by the PA treated thoracic aorta and the mesenteric arteries was higher than the control group. These results demonstrated that chronic treatment with a PA water extract to middle-aged rats affected their vascular functions by increasing the nitric oxide production from the endothelial cells and also modulated the responsiveness of the thoracic aortic- and mesenteric rings to phenylephrine and acetylcholine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Organic mononitrites of 1,2-propanediol act as an effective NO-releasing vasodilator in pulmonary hypertension and exhibit no cross-tolerance with nitroglycerin in anesthetized pigs

    Directory of Open Access Journals (Sweden)

    Nilsson KF

    2018-03-01

    Full Text Available Kristofer F Nilsson,1,2 Waldemar Goździk,3 Claes Frostell,4 Stanisław Zieliński,3 Marzena Zielińska,3 Kornel Ratajczak,5 Piotr Skrzypczak,5 Sylwia Rodziewicz,5 Johanna Albert,6 Lars E Gustafsson1,† 1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; 2Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland; 4Department of Anesthesia and Intensive Care, Danderyd Hospital, Stockholm, Sweden; 5Department and Clinic of Surgery, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland; 6Department of Surgery, Danderyd Hospital, Stockholm, Sweden †Lars E Gustafsson passed away on October 04, 2017 Purpose: Clinically available intravenous (IV nitric oxide (NO donor drugs such as nitroglycerin (GTN cause systemic hypotension and/or tolerance development. In a porcine model, novel NO donor compounds – the organic mononitrites of 1,2-propanediol (PDNO – were compared to GTN with regard to pulmonary selectivity and tolerance development. The vasodilatory effects of inorganic nitrite were investigated.Materials and methods: In anesthetized piglets, central hemodynamics were monitored. At normal pulmonary vascular resistance (PVR, IV infusions of PDNO (15–60 nmol kg-1 min-1, GTN (13–132 nmol kg-1 min-1, and inorganic nitrite (dosed as PDNO were administered. At increased PVR (by U46619 IV, IV infusions of PDNO (60–240 nmol kg-1 min-1 and GTN (75–300 nmol kg-1 min-1 before and after a 5 h infusion of GTN (45 nmol kg-1 min-1 were given.Results: At normal PVR, PDNO (n=12 and GTN (n=7 caused significant dose-dependent decreases in mean systemic and pulmonary arterial pressures, whereas inorganic nitrite (n=13 had no significant effect. At increased PVR, PDNO (n=6 and GTN (n=6 significantly decreased mean systemic and pulmonary

  5. Severe Hypertension and Bradycardia Secondary to Midodrine Overdose.

    Science.gov (United States)

    Wong, L Y; Wong, A; Robertson, T; Burns, K; Roberts, M; Isbister, G K

    2017-03-01

    The objective of this case is to describe the pharmacokinetics and toxicity of midodrine in overdose. A 20 year old female ingested up to 350 mg midodrine while recovering in hospital from another overdose. She developed vomiting and severe hypertension (blood pressure [BP], 210/100 mmHg). Remarkable findings included a heart rate with a range of 43-60 beats/min, spontaneous respirations (20 breaths/min), and oxygen saturations of >95 % on FiO2 25 %, and a GS of 8. She was admitted to intensive care and had a normal non-contrast CT brain. She was treated with a glyceryl trinitrate patch (5 mg) and observed for 36 h with subsequent BP reduction to 124/81 mmHg and improved in conscious state. Midodrine and desglymidodrine concentrations were measured with liquid chromatography tandem mass spectrometry and were detected with 2-h post-ingestion at concentrations of 158.4 and 169.7 ng/mL, respectively. The parent drug concentrations rapidly decreased with an elimination of half-life of 1.6 h, and the metabolite initially increased and then decreased. The peak in blood pressure appeared to coincide with peak metabolite concentrations. Midodrine in overdose can potentially cause severe hypertension and reflex bradycardia but given its short half-life treatment with vasodilator agents and supportive care is sufficient.

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

    Science.gov (United States)

    Gori, Tommaso; Daiber, Andreas

    2009-01-01

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

  7. Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/- mice

    Directory of Open Access Journals (Sweden)

    Stalleicken Dirk

    2006-11-01

    Full Text Available Abstract Background Chronic therapy with nitroglycerin (GTN results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS. According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2 play an important role for the development of nitrate and cross-tolerance. Methods Tolerance was induced by infusion of wild type (WT and heterozygous manganese superoxide dismutase mice (Mn-SOD+/- with ethanolic solution of GTN (12.5 μg/min/kg for 4 d. For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 17.5 μg/min/kg for 4 d was infused in DMSO. Vascular reactivity was measured by isometric tension studies of isolated aortic rings. ROS formation and aldehyde dehydrogenase (ALDH-2 activity was measured in isolated heart mitochondria. Results Chronic GTN infusion lead to impaired vascular responses to GTN and acetylcholine (ACh, increased the ROS formation in mitochondria and decreased ALDH-2 activity in Mn-SOD+/- mice. In contrast, PETN infusion did not increase mitochondrial ROS formation, did not decrease ALDH-2 activity and accordingly did not lead to tolerance and cross-tolerance in Mn-SOD+/- mice. PETN but not GTN increased heme oxygenase-1 mRNA in EA.hy 926 cells and bilirubin efficiently scavenged GTN-derived ROS. Conclusion Chronic GTN infusion stimulates mitochondrial ROS production which is an important mechanism leading to tolerance and cross-tolerance. The tetranitrate PETN is devoid of mitochondrial oxidative stress induction and according to the present animal study as well as numerous previous clinical studies can be used without limitations due to tolerance and cross-tolerance.

  8. Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

    Science.gov (United States)

    Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

    2015-09-01

    To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Ashina, Messoud

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Heng

    2016-02-01

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

  11. Gestational trophoblastic neoplasia: efficacy of color doppler ultrasound

    International Nuclear Information System (INIS)

    Song, Sun Wha; Jee, Won Hee; Choe, Bo Young; Byun, Jae Young; Choi, Byung Gil; Shinn, Kyung Sub

    1997-01-01

    To evaluate the efficacy of color Doppler ultrasound (US) in the diagnosis of gestational trophoblastic neoplasia (GTN). Intralesional color flows and resistive index (RI) on color Doppler US were prospectively analyzed in 21 consecutive suspected GTN cases. RI of the intralesional artery was investigated on the basis of the presence or absence of mass and metastasis. Correlation between RI of intralesional artery and urinary β-hCG was also investigated. Intralesional color flows were identified in 15 patients with GTN. On operation, intralesional color flows were observed in one of two patients in whom the presence of completely necrotic tissue was confirmed. Intralesional color flows, however, were not detected in four patients who were proved not to be GTN sufferers. Sensitivity, specificity, accuracy, positive and negative predictive values, and accuracy were 100%, 83%, 95%, 94% and 100%, respectively. Significant correlation between RI of the intralesional artery and urinary β-hCG was not established (p=0.49, r=0.19). RI of this artery was not substantially different between groups with and without mass, and between groups with and without metastasis (p=0.32, p=0.82). The current study demonstrates that color Doppler US is a sensitive and useful method for the diagnosis of GTN

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

    Science.gov (United States)

    Ballmann, C; Mueller, B W

    2008-01-01

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

  13. Monoglycerides and fatty acids from Ibervillea sonorae root: isolation and hypoglycemic activity.

    Science.gov (United States)

    Hernández-Galicia, Erica; Calzada, Fernando; Roman-Ramos, Rubén; Alarcón-Aguilar, Francisco J

    2007-03-01

    Eleven monoglycerides (MG), 1-monopalmitin (1), glyceryl 1-monomargarate (2), 1-monostearin (3), glyceryl 1-monononadecylate ( 4), glyceryl 1-monoarachidate (5), glyceryl 1-monobehenate (6), glyceryl 1-monotricosanoate (7), glyceryl 1-monotetracosanoate (8), glyceryl 1-monopentacosanoate (9), glyceryl 1-monohexacosanoate (10) and glyceryl 1-monooctacosanoate (11), together with five fatty acids (FA), lauric acid (12), myristic acid (13), pentadecanoic acid (14), palmitic acid (15) and stearic acid (16) were isolated of the root of IBERVILLEA SONORAE Greene (Cucurbitaceae). Their structures were determined by spectroscopic and chemical methods as well as GC-MS analysis. The hypoglycemic activity of the dichloromethane (DCM) extract, of fractions (F1-F10 and SF1-SF5), of monoglycerides (MG) and of fatty acids (FA) mixtures obtained of the root from I. SONORAE was evaluated in normoglycemic and alloxan-induced diabetic mice. The results showed that by intraperitoneal administration the DCM extract (300 mg/kg), F9 (300 mg/kg) and SF1 (150 mg/kg) significantly reduced glucose levels in both models. For fraction SF1, the hypoglycemic activity was more pronounced than that of tolbutamide (150 mg/kg) used as control. However, neither MG (75 mg/kg) nor FA (75 mg/kg) mixtures isolated from SF1 exhibited a significant hypoglycemic effect. However, when MG and FA were combined in equal proportions (75 mg: 75 mg/kg), their effect was comparable to that of SF1. The observed activity for the DCM extract, F9, SF1 and the MG-FA mixture provides additional support for the popular use of this plant in the treatment of diabetes mellitus in Mexican traditional medicine.

  14. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

    Science.gov (United States)

    Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

    2015-11-01

    To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CInormalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CInormalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Comparison of the Effect of 5 Different Treatment Options for Managing Patellar Tendinopathy: A Secondary Analysis.

    Science.gov (United States)

    van Rijn, Dafne; van den Akker-Scheek, Inge; Steunebrink, Mirjam; Diercks, Ron L; Zwerver, Johannes; van der Worp, Henk

    2017-10-10

    Currently, no treatments exist for patellar tendinopathy (PT) that guarantee quick and full recovery. Our objective was to assess which treatment option provides the best chance of clinical improvement and to assess the influence of patient and injury characteristics on the clinical effect of these treatments. A secondary analysis was performed on the combined databases of 3 previously performed double-blind randomized controlled trials. In total, 138 patients with PT were included in the analysis. Participants were divided into 5 groups, based on the treatment they received: Extracorporeal shockwave therapy (ESWT) (n = 31), ESWT plus eccentric training (n = 43), eccentric training (n = 17), topical glyceryl trinitrate patch plus eccentric training (n = 16), and placebo treatment (n = 31). Clinical improvement (increase of ≥13 points on the Victorian Institute of Sport Assessment-Patella score) after 3 months of treatment. Fifty-two patients (37.7%) improved clinically after 3 months of treatment. Odds ratios (ORs) for clinical improvement were significantly higher in the eccentric training group (OR 6.68, P = 0.009) and the ESWT plus eccentric training group (OR 5.42, P = 0.015) compared with the other groups. We found evidence that a high training volume, a longer duration of symptoms, and older age negatively influence a treatment's clinical outcome (trend toward significance). Our study confirmed the importance of exercise, and eccentric training in particular, in the management of PT. The role of ESWT remains uncertain. Further research focusing on the identified prognostic factors is needed to be able to design patient-specific treatment protocols for the management of PT.

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

    Science.gov (United States)

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

    2014-11-01

    In type 2 diabetes patients, endothelin (ET) receptor blockade may enhance blood flow responses to exercise training. The combination of exercise training and ET receptor blockade may represent a more potent stimulus than training alone to improve vascular function, physical fitness and glucose homeostasis. We assessed the effect of an 8 week exercise training programme combined with either ET blockade or placebo on vasculature, fitness and glucose homeostasis in people with type 2 diabetes. In a double-blind randomized controlled trial, brachial endothelium-dependent and ‑independent dilatation (using flow-mediated dilatation and glyceryl trinitrate, respectively), glucose homeostasis (using Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)) and physical fitness (maximal cycling test) were assessed in 18 men with type 2 diabetes (60 ± 6 years old). Subjects underwent an 8 week exercise training programme, with half of the subjects receiving ET receptor blockade (bosentan) and the other half a placebo, followed by reassessment of the tests above. Exercise training improved physical fitness to a similar extent in both groups, but we did not detect changes in vascular function in either group. This study suggests that there is no adaptation in brachial and femoral artery endothelial function after 8 weeks of training in type 2 diabetes patients. Endothelin receptor blockade combined with exercise training does not additionally alter conduit artery endothelial function or physical fitness in type 2 diabetes. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  17. Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.

    LENUS (Irish Health Repository)

    Winter, D C

    2012-02-03

    PURPOSE: The use of transanal stapling devices may impair continence because of digital dilatation and\\/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion. METHODS: A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography. RESULTS: Intraoperative mean (+\\/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +\\/- 0.9 vs. 50.5 +\\/- 2.7; P = 0.002) or controls (56.0 +\\/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +\\/- 3.2 - 31.6 +\\/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +\\/- 0.2 vs. 4.6 +\\/- 0.3; P = 0.003) and 12-month (0.9 +\\/- 0.1 vs. 4.4 +\\/- 0.3; P = 0.002) clinic visits. CONCLUSION: Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.

  18. Proctalgia fugax, an evidence-based management pathway.

    Science.gov (United States)

    Jeyarajah, Santhini; Chow, Andre; Ziprin, Paul; Tilney, Henry; Purkayastha, Sanjay

    2010-09-01

    Proctalgia fugax (PF) is a benign anorectal condition which has been described in the literature since the nineteenth century commonly presenting to general surgeons. There is little high level evidence on the subject and its therapeutic modalities. We aimed through this systematic literature review to outline the definition and diagnostic criteria of this condition, the aetiology and differential diagnoses and describe the different treatment modalities that have been attempted and their success. A literature search of Google Scholar and Medline using Pubmed as the search engine was used to identify all studies directly related to the definition, aetiology and treatment options for this condition (latest at 12 August 2008) was performed. The search produced 61 references with three others obtained from the references of these papers. The prevalence of PF in the general population ranges from 4% to 18%. The diagnosis is based on the presence of characteristic symptoms as defined by Rome III guidelines and physical examination. The mainstay of treatment is reassurance and careful counselling with evidence in the literature for warm baths, topical treatment with glyceryl trinitrate or diltiazem and salbutamol inhalation. In persistent cases, local anaesthetic blocks, clonidine or Botox injections can be considered after clarification of risk and benefit. Based on this we suggest that diagnosis should be made through exclusion of common organic causes such as haemorrhoids, anal fissure or anorectal carcinoma and on the fulfillment of Rome III criteria. The main treatment for this benign condition remains reassurance and topical treatment.

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

    Science.gov (United States)

    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.

  20. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  1. Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern--A case report.

    Science.gov (United States)

    Nikolić, Branka; Ćurković, Aleksandar; Dikić, Svetlana Dragojević; Mitrović, Ana; Kuzmanović, Igor; Arandjelović, Aleksandra; Stanković, Goran

    2015-07-01

    Gestational trophoblastic neoplasm (GTN), choriocarcinoma in coexistence with primary cervical adenocarcinoma, is a rare event not easy to diagnose. Choriocarcinoma is a malignant form of GTN but curable if metastases do not appear early and spread fast. We presented choriocarcinoma in coexistence with primary cervical adenocarcinoma in a 48-year-old patient who had radical hysterectomy because of confirmed cervical carcinoma (Dg: Carcinomaporo vaginalis uteri FIGO st I B1). Histological findings confirmed cervical choriocarcinoma with extensive vascular invasion and apoptosis but GTN choriocarcinoma was finally confirmed after immunohystochemical examinations. Preoperative serum human gonadotropine (beta hCG) level stayed unknown. This patient did not have any pregnancy-like symptoms before the operation. The first beta hCG monitoring was done two months after the operation and found negative. According to the final diagnosis the decision of Consilium for Malignant Diseases was that this patient needed serum hCG monitoring as well as treatment with chemotherapy for high-risk GTN and consequent irradiation for adenocarcinoma. The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis.

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

    OpenAIRE

    Ellaithy, H. M.; El-Shaboury, K. M. F.

    2002-01-01

    The influence of the vehicle on the release and permeation of fluconazole, a topical antifungal drug dissolved in Jojoba oil was evaluated. Series of Cutina lipogels (Cutina CPA [cetyl palmitate], CBS [mixture of glyceryl stearate, cetearyl alcohol, cetyl palmitate, and cocoglycerides], MD [glyceryl stearate], and GMS [glyceryl monostearate]) in different concentrations as well as gel microemulsion were prepared. In-vitro drug release in Sorensens citrate buffer (pH 5.5) and permeation throug...

  3. The Genotype of the Donor for the (GTn 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.

    Directory of Open Access Journals (Sweden)

    Víctor Noriega

    Full Text Available 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 (≤(GT15 for the (GTn 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.

  4. Multiple pregnancies with complete mole and coexisting normal fetus in North and South America: A retrospective multicenter cohort and literature review.

    Science.gov (United States)

    Lin, Lawrence H; Maestá, Izildinha; Braga, Antonio; Sun, Sue Y; Fushida, Koji; Francisco, Rossana P V; Elias, Kevin M; Horowitz, Neil; Goldstein, Donald P; Berkowitz, Ross S

    2017-04-01

    To determine the clinical characteristics of multiple gestation with complete mole and coexisting fetus (CHMCF) in North and South America. Retrospective non-concurrent cohorts compromised of CHMCF from New England Trophoblastic Disease Center (NETDC) (1966-2015) and four Brazilian Trophoblastic Disease Centers (BTDC) (1990-2015). From a total of 12,455 cases of gestational trophoblastic disease seen, 72 CHMCF were identified. Clinical characteristics were similar between BTDC (n=46) and NETDC (n=13) from 1990 to 2015, apart from a much higher frequency of potentially life-threatening conditions in Brazil (p=0.046). There were no significant changes in the clinical presentation or outcomes over the past 5 decades in NETDC (13 cases in 1966-1989 vs 13 cases in 1990-2015). Ten pregnancies were electively terminated and 35 cases resulted in viable live births (60% of 60 continued pregnancies). The overall rate of gestational trophoblastic neoplasia (GTN) was 46%; the cases which progressed to GTN presented with higher chorionic gonadotropin levels (p=0.026) and higher frequency of termination of pregnancy due to medical complications (p=0.006) when compared to those with spontaneous remission. The main regional difference in CHMCF presentation is related to a higher rate of potentially life-threatening conditions in South America. Sixty percent of the expectantly managed CHMCF delivered a viable infant, and the overall rate of GTN in this study was 46%. Elective termination of pregnancy did not influence the risk for GTN; however the need for termination due to complications and higher hCG levels were associated with development of GTN in CHMCF. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    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.

  6. Physicochemical Properties of α-Form Hydrated Crystalline Phase of 3-(10-Carboxydecyl)-1,1,1,3,5,5,5-heptamethyl Trisiloxane/Higher alcohol/Polyoxyethylene (5 mol) Glyceryl monostearate/Water System.

    Science.gov (United States)

    Uyama, Makoto; Araki, Hidefumi; Fukuhara, Tadao; Watanabe, Kei

    2018-06-07

    The α-form hydrated crystalline phase (often called as an α-gel) is one of the hydrated crystalline phases which can be exhibited by surfactants and lipids. In this study, a novel system of an α-form hydrated crystal was developed, composed of 3-(10-carboxydecyl)-1,1,1,3,5,5,5-heptamethyl trisiloxane (CDTS), polyoxyethylene (5 mol) glyceryl monostearate (GMS-5), higher alcohol. This is the first report to indicate that a silicone surfactant can form an α-form hydrated crystal. The physicochemical properties of this system were characterized by small and wide angle X-ray scattering (SWAXS), differential scanning calorimetry (DSC), and diffusion-ordered NMR spectroscopy (DOSY) experiments. SWAXS and DSC measurements revealed that a plurality of crystalline phases coexist in the CDTS/higher alcohol/water ternary system. By adding GMS-5 to the ternary system, however, a wide region of a single α-form hydrated crystalline phase was obtained. The self-diffusion coefficients (D sel ) from the NMR measurements suggested that all of the CDTS, GMS-5, and higher alcohol molecules were incorporated into the same α-form hydrated crystals.

  7. Comparing Mycobacterium tuberculosis genomes using genome topology networks.

    Science.gov (United States)

    Jiang, Jianping; Gu, Jianlei; Zhang, Liang; Zhang, Chenyi; Deng, Xiao; Dou, Tonghai; Zhao, Guoping; Zhou, Yan

    2015-02-14

    Over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. Several findings have revealed that genomic structural variations (SVs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by SVs may extend our knowledge of the relationships between SVs and phenotypes in microbes, especially in pathogenic bacteria. In this work, we introduce a 'Genome Topology Network' (GTN) method based on gene homology and gene locations to analyze genomic SVs and perform phylogenetic analysis. Furthermore, the concept of 'unfixed ortholog' has been proposed, whose members are affected by SVs in genome topology among close species. To improve the precision of 'unfixed ortholog' recognition, a strategy to detect annotation differences and complete gene annotation was applied. To assess the GTN method, a set of thirteen complete M. tuberculosis genomes was analyzed as a case study. GTNs with two different gene homology-assigning methods were built, the Clusters of Orthologous Groups (COG) method and the orthoMCL clustering method, and two phylogenetic trees were constructed accordingly, which may provide additional insights into whole genome-based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most members were related to immunogenicity and drug resistance, such as PPE-repeat proteins (COG5651) and transcriptional regulator TetR gene family members (COG1309). The GTN method has been implemented in PERL and released on our website. The tool can be downloaded from http://homepage.fudan.edu.cn/zhouyan/gtn/ , and allows re-annotating the 'lost' genes among closely related genomes, analyzing genes affected by SVs, and performing phylogenetic analysis. With this tool, many immunogenic-related and drug resistance-related genes

  8. A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

    Science.gov (United States)

    Wiltshire, Esko J; Peña, Alexia S; MacKenzie, Karen; Bose-Sundernathan, Tulika; Gent, Roger; Couper, Jennifer J

    2015-02-01

    To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

    Science.gov (United States)

    Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

    2010-11-02

    Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; Pwomen with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

  10. Effects of nifedipine on anorectal smooth muscle in vitro.

    Science.gov (United States)

    Cook, T A; Brading, A F; Mortensen, N J

    1999-06-01

    Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

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

    Science.gov (United States)

    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

  12. Hexaaquagallium(III trinitrate trihydrate

    Directory of Open Access Journals (Sweden)

    Jason D. Masuda

    2009-08-01

    Full Text Available The title compound, [Ga(H2O6](NO33·3H2O, is isostructural to other known MIII nitrate hydrates (M = Al, Cr, Fe. The structure contains two distinct octahedral Ga(OH26 units (each of overline{1} symmetry which are involved in intermolecular hydrogen bonding with the three nitrate anions and three water molecules within the asymmetric unit.

  13. Triploidy--Observations in 154 Diandric Cases.

    Directory of Open Access Journals (Sweden)

    Nanna Brink Scholz

    Full Text Available 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%.

  14. Ductile failure analysis of high strength steel in hot forming based on micromechanical damage model

    Directory of Open Access Journals (Sweden)

    Ying Liang

    2016-01-01

    Full Text Available The damage evolution of high strength steel at elevated temperature is investigated by using the Gurson-Tvergaard-Needleman (GTN model. A hybrid method integrated thermal tensile test and numerical technique is employed to identify the damage parameters. The analysis results show that the damage parameters are different at different temperature as the variation of tested material microstructure. Furthermore, the calibrated damage parameters are implemented to simulate a bugling forming at elevated temperature. The experimental results show the availability of GTN damage model in analyzing sheet formability in hot forming.

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

    Science.gov (United States)

    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

  16. The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Talman W.T.

    1997-01-01

    Full Text Available Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO, S-nitrosoacetylpenicillamine (SNAP, and S-nitroso-D-cysteine (D-SNC produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1 the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2 L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  18. Cohesive traction-separation relations for plate tearing under mixed mode loading

    DEFF Research Database (Denmark)

    Andersen, R. G.; Woelke, P. B.; Nielsen, K. L.

    2018-01-01

    The present study investigates a sequence of failure events related to steady-state tearing of large-scale ductile plates by employing the micro-mechanics based Gurson-Tvergaard-Needleman (GTN) model. The fracture process in front of an advancing crack is approximated by a series of 2D plane strain...... finite element models to facilitate a comprehensive study of mixed mode fracture behavior as well as a parameter study of the cohesive energy and tractions involved in the process. The results from the conducted GTN model simulations are used to define cohesive zone models suitable for plate tearing...

  19. Neuroprotective effects of glyceryl nonivamide against microglia-like cells and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells.

    Science.gov (United States)

    Lin, Yi-Chin; Uang, Hao-Wei; Lin, Rong-Jyh; Chen, Ing-Jun; Lo, Yi-Ching

    2007-12-01

    Glyceryl nonivamide (GLNVA), a vanilloid receptor (VR) agonist, has been reported to have calcitonin gene-related peptide-associated vasodilatation and to prevent subarachnoid hemorrhage-induced cerebral vasospasm. In this study, we investigated the neuroprotective effects of GLNVA on activated microglia-like cell mediated- and proparkinsonian neurotoxin 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. In coculture conditions, we used lipopolysaccharide (LPS)-stimulated BV-2 cells as a model of activated microglia. LPS-induced neuronal death was significantly inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase. However, capsazepine, the selective VR1 antagonist, did not block the neuroprotective effects of GLNVA. GLNVA reduced LPS-activated microglia-mediated neuronal death, but it lacked protection in DPI-pretreated cultures. GLNVA also decreased LPS activated microglia induced overexpression of neuronal nitric-oxide synthase (nNOS) and glycoprotein 91 phagocyte oxidase (gp91(phox)) on SH-SY5Y cells. Pretreatment of BV-2 cells with GLNVA diminished LPS-induced nitric oxide production, overexpression of inducible nitric-oxide synthase (iNOS), and gp91(phox) and intracellular reactive oxygen species (iROS). GLNVA also reduced cyclooxygenase (COX)-2 expression, inhibitor of nuclear factor (NF)-kappaB (IkappaB)alpha/IkappaBbeta degradation, NF-kappaB activation, and the overproduction of tumor necrosis factor-alpha, interleukin (IL)-1beta, and prostaglandin E2 in BV-2 cells. However, GLNVA augmented anti-inflammatory cytokine IL-10 production on LPS-stimulated BV-2 cells. Furthermore, in 6-OHDA-treated SH-SY5Y cells, GLNVA rescued the changes in condensed nuclear and apoptotic bodies, prevented the decrease in mitochondrial membrane potential, and reduced cells death. GLNVA also suppressed accumulation of iROS and up-regulated heme oxygenase-1 expression. 6-OHDA-induced overexpression of nNOS, i

  20. Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

    Directory of Open Access Journals (Sweden)

    Ruangweerayut Ronnatrai

    2010-09-01

    Full Text Available Abstract Background Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GTn repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription as well as polymorphism of TNF were investigated. Methods Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM and 80 cases with Plasmodium vivax malaria (VM, and 77 cases with severe or cerebral malaria (SM for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3% Thai, 243 (50.0% Burmese and 120 (24.7% Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand. Results The number of (GTn repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S, medium (M and long (L GTn repeats. The genotype of (GTn repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed. Conclusions Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria

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

    Science.gov (United States)

    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 (metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals.

  2. Internationally coordinated glacier monitoring - a timeline since 1894

    Science.gov (United States)

    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

  3. Polyiodinated triglycerides for CT of the liver

    International Nuclear Information System (INIS)

    Weichert, J.P.; Longino, M.A.; Ullrich, K.A.; Schwendner, S.W.; Glazer, G.M.; Counsell, R.E.

    1989-01-01

    Several polyiodinated aryl triglyceride analogs have been synthesized, radioiodinated, emulsified, and administered to rats and normal or tumor-bearing rabbits in tracer or radiologic doses for tissue distribution (TD) and CT studies. The authors present preliminary TD results in rats with three of these analogs: glyceryl 1,3-diiopanoyl 2-palmitate; glyceryl 1,3-diiopanoyl 2-oleate; and glyceryl 1,3-di-7-(3-amino-2,4,6-triiodophenyl) heptanoyl 2-oleate. Respectively, 74%, 28%, and 55% of the injected radioactivity was present in the liver 1/2 hours after administration. Chemical structure and method of formulation bad a pronounced effect on the uptake, metabolism, and clearance properties of the agent. Initial CT studies with analog 1 (32 mg I/kg) in rabbits bearing hepatic VX2 tumors revealed tumors ranging in diameter from 0.3 to 3 cm

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

    Science.gov (United States)

    Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

    2014-12-01

    Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The preparation by extrusion/spheronization and the properties of pellets containing drugs, microcrystalline cellulose and glyceryl monostearate.

    Science.gov (United States)

    Chatchawalsaisin, Jittima; Podczeck, Fridrun; Newton, J Michael

    2005-01-01

    Pellets have been prepared by extrusion and spheronization containing microcrystalline cellulose (MCC) and four model drugs with decreasing order of solubility, paracetamol (P), diclofenac sodium (D), ibuprofen (IB) and indomethacin (IN) at a 10% level with and without the addition of a range of levels of glyceryl monostearate (GMS). The drugs differed in their response to extrusion in that all formulations containing the drug D had a 'steady state' extrusion profile whereas the other three drugs exhibited 'forced flow' indicating the possibility of water migration during the process of ram extrusion. The presence of GMS did not influence this effect. The drug D also required consistently less water to function than the other three drugs. In spite of these differences in extrusion performance, it was possible to prepare satisfactory pellets from formulations of all the drugs with 0, 30 and 60% GMS combined with 90, 60 or 30% of MCC at a range of water levels. It was also possible to prepare pellets containing the drug D with 70, 80 and 90% GMS, with corresponding quantities of 20, 10 and 0% of MCC. It was also possible to prepare the pellet formulations by dispersing the drugs in molten GMS, grinding and processing this with MCC and water. Such systems retained the processing characteristics of the composition made by the blending of the powder. The presence of GMS in all cases reduced the quantity of water required for the process to function. The steady state or the mean of the range of the forces observed during forced flow, were dependent on the composition and the quantity of water added. The surface of the extrudate appeared smooth and measurements of surface roughness established that the value of the rugosity R(a) for any of the extrudates did not exceed 6 microm. The extrudate diameter was found to increase with the quantity of GMS in the formulation. The pellets produced were all within a relatively narrow size range (three sieve fractions of a root two

  6. The crystal structure of XdpB, the bacterial old yellow enzyme, in an FMN-free form

    Czech Academy of Sciences Publication Activity Database

    Zahradník, Jiří; Kolenko, P.; Palyzová, Andrea; Černý, J.; Kolářová, L.; Kyslíková, Eva; Marešová, Helena; Grulich, Michal; Nunvář, J.; Šulc, M.; Kyslík, Pavel; Schneider, B.

    2018-01-01

    Roč. 13, č. 4 (2018), č. článku e0195299. E-ISSN 1932-6203 Institutional support: RVO:61388971 Keywords : GLYCEROL TRINITRATE REDUCTASE * N-ETHYLMALEIMIDE REDUCTASE * OXIDATIVE STRESS-RESPONSE Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.806, year: 2016

  7. Identification and application of Gurson–Tvergaard–Needleman model for sub-sized three-point- bend geometry

    Czech Academy of Sciences Publication Activity Database

    Stratil, Luděk; Hadraba, Hynek; Kozák, Vladislav; Dlouhý, Ivo

    2013-01-01

    Roč. 58, č. 2 (2013), s. 141-155 ISSN 0001-7043 Institutional support: RVO:68081723 Keywords : GTN model, Eurofer97 * smooth tensile test * J–R curve * KLST specimen Subject RIV: JL - Materials Fatigue, Friction Mechanics

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

    Directory of Open Access Journals (Sweden)

    Mei Peng

    Full Text Available 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.

  9. A curva de regressão da gonadotrofina coriônica humana é útil no diagnóstico precoce da neoplasia trofoblástica gestacional pós-molar? Are curves of human chorionic gonadotropin useful in the early diagnosis of post-molar trophoblastic neoplasia?

    Directory of Open Access Journals (Sweden)

    Lúcia Regina Marques Gomes Delmanto

    2007-10-01

    Full Text Available OBJETIVO: avaliar a utilidade da curva de regressão normal da gonadotrofina coriônica humana (hCG no diagnóstico precoce de neoplasia trofoblástica gestacional pós-molar (NTG. MÉTODOS: estudo longitudinal, incluindo 105 pacientes com mola hidatiforme completa (MHC acompanhadas no Centro de Doenças Trofoblásticas de Botucatu, entre 1998 e 2005. Os títulos da hCG sérica foram mensurados quinzenalmente em todas as pacientes. Curvas individuais de regressão da hCG das 105 pacientes foram estabelecidas. A comparação entre a curva de regressão normal estabelecida em nosso serviço com as curvas individuais da hCG foi usada no rastreamento e diagnóstico (platô/ascensão de NTG. O número de semanas pós-esvaziamento quando a hCG excedeu o limite normal foi comparado com o número semanas em que a hCG apresentou platô/ascensão. RESULTADOS: das 105 pacientes com MHC, 80 apresentaram remissão espontânea (RE e 25 desenvolveram NTG. Das 80 pacientes com RE, 7 (8,7% apresentaram, inicialmente, dosagem da hCG acima do normal, mas, no devido tempo, alcançaram a remissão. Todas as 25 pacientes com NTG apresentaram desvio da curva normal da hCG em 3,8±2,5 semanas e mostraram platô ou ascensão em 8,4±2,9 semanas (pPURPOSE: to evaluate the usefulness of the normal human chorionic gonadotropin (hCG regression curve in the early diagnosis of post-molar trophoblastic neoplasia (GTN. METHODS: a longitudinal study including 105 patients with complete hydatidiform mole (CHM followed up at the Botucatu Center of Trophoblastic Diseases from 1998 to 2005. Serial serum hCG titers were measured fortnightly in all patients. Individual curves of the 105 patients were built. Comparison between the normal regression curve established at our center with individual hCG curves was used to screen and diagnose (plateau/rise GTN. The number of weeks postevacuation when hCG levels exceeded the normal limits was compared with the number of weeks when h

  10. Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

    Science.gov (United States)

    Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

    2018-05-03

    Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Data Integration Tool: From Permafrost Data Translation Research Tool to A Robust Research Application

    Science.gov (United States)

    Wilcox, H.; Schaefer, K. M.; Jafarov, E. E.; Strawhacker, C.; Pulsifer, P. L.; Thurmes, N.

    2016-12-01

    The United States National Science Foundation funded PermaData project led by the National Snow and Ice Data Center (NSIDC) with a team from the Global Terrestrial Network for Permafrost (GTN-P) aimed to improve permafrost data access and discovery. We developed a Data Integration Tool (DIT) to significantly speed up the time of manual processing needed to translate inconsistent, scattered historical permafrost data into files ready to ingest directly into the GTN-P. We leverage this data to support science research and policy decisions. DIT is a workflow manager that divides data preparation and analysis into a series of steps or operations called widgets. Each widget does a specific operation, such as read, multiply by a constant, sort, plot, and write data. DIT allows the user to select and order the widgets as desired to meet their specific needs. Originally it was written to capture a scientist's personal, iterative, data manipulation and quality control process of visually and programmatically iterating through inconsistent input data, examining it to find problems, adding operations to address the problems, and rerunning until the data could be translated into the GTN-P standard format. Iterative development of this tool led to a Fortran/Python hybrid then, with consideration of users, licensing, version control, packaging, and workflow, to a publically available, robust, usable application. Transitioning to Python allowed the use of open source frameworks for the workflow core and integration with a javascript graphical workflow interface. DIT is targeted to automatically handle 90% of the data processing for field scientists, modelers, and non-discipline scientists. It is available as an open source tool in GitHub packaged for a subset of Mac, Windows, and UNIX systems as a desktop application with a graphical workflow manager. DIT was used to completely translate one dataset (133 sites) that was successfully added to GTN-P, nearly translate three datasets

  12. The effect of propranolol on glyceryltrinitrate-induced headache and arterial response

    DEFF Research Database (Denmark)

    Tvedskov, Jesper; Thomsen, L L; Thomsen, L L

    2004-01-01

    Prophylactic drug trials in migraine are long-lasting and expensive and require long-term toxicology information. A human migraine model would therefore be helpful in testing new drugs. Immediate headache and delayed migraine after glyceryltrinitrate (GTN) has been well characterized. We have rec...

  13. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

    Science.gov (United States)

    Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

    2003-08-01

    Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

  14. Outcome of pregnancy subsequent to chemotherapy with actinomycin-D in low risk gestational trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2017-07-01

    Methods: A retrospective cohort study was conducted on patients with GTN who were referred to Firoozgar and Mirza Koochak Khan teaching hospitals during 10 years, starting from 2004. The inclusion criterion was patients with low-risk persistent GTN after molar pregnancy, EP, and abortion, that treated with single agent chemotherapy actinomycin-D. After following the patients for 12 months, patients with serum βHCG lower than 5 mIU/ml, who intended to have child were allowed to become pregnant. The following items were observed in the study: age, body mass index (BMI, parity, chemotherapy duration, and pregnancy outcomes such as spontaneous abortion or preterm labor, pre-eclampsia, stillbirth, fetal malformation, and repeated molar pregnancy. Results: 74 patients were monitored, 83.78% of them had uncomplicated pregnancy and labor, 4.05% had the abortion, 4.05% had second molar pregnancy, 2.7% had pre-eclampsia, 5.40% had preterm labor. Moreover, stillbirth and malformation did not occur in this study even after chemotherapy treatment. There was not any significant correlation between age, BMI, parity, and chemotherapy duration with pregnancy outcomes. Conclusion: The outcomes of pregnancy after chemotherapy with actinomycin-D is similar to the general population who did not have chemotherapy. The abortion rate and repeated molar pregnancy were similar between population and sample too. Thus, the study shows that the cured patients with low-risk GTN have as much chance of having a normal pregnancy as normal women. In other words, treatment with actinomycin-D does not have any adverse effect in future pregnancies.

  15. TropJrnal Vol 32 No 1 PDF

    African Journals Online (AJOL)

    Mr Olusoji

    all cases of suspected molar pregnancy to have histologic eonfinnation. Thorough evaluation of the clinical notes was done. All cases of Gestational. Trophoblastic Ncoplasia(GTN) were excluded. Anaemia was defined as packed cell volume less than 30"10. Infonnation regarding the demographic characteristics, clinical ...

  16. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia.

    Science.gov (United States)

    Wang, Qiuyi; Fu, Jing; Hu, Lina; Fang, Fang; Xie, Lingxia; Chen, Hengxi; He, Fan; Wu, Taixiang; Lawrie, Theresa A

    2017-09-11

    This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear. To evaluate the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy. To investigate whether any subgroup of women with HM may benefit more from P-Chem than others. For the original review we performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and Embase (1980 to 2012, week 9). We developed the search strategy using free text and MeSH. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2017), MEDLINE (February 2012 to June week 1, 2017) and Embase (February 2012 to 2017, week 23). We also handsearched reference lists of relevant literature to identify additional studies and searched trial registries. We included randomised controlled trials

  17. A ductile fracture analysis using a local damage model

    Energy Technology Data Exchange (ETDEWEB)

    Benseddiq, N. [Laboratoire de Mecanique et de Rheologie de Tours, Ecole Nationale d' Ingenieurs du Val de Loire (ENIVL), Rue de la Chocolaterie, 41000 Blois Cedex (France)], E-mail: nbensedd@polytech-lille.fr; Imad, A. [Laboratoire de Mecanique de Lille (UMR CNRS 8107), USTL, Ecole Polytechnique Universitaire de Lille Cite Scientifique, Avenue P. Langevin, 59655 Villeneuve d' Ascq Cedex (France)

    2008-04-15

    In this study, the Gurson-Tvergaard-Needleman (GTN) model is used to investigate ductile tearing. The sensitivity of the model parameters has been examined from literature data. Three types of parameters have been reported: the 'constitutive parameters'q{sub 1}, q{sub 2} and q{sub 3}, the 'initial material and nucleation parameters' and the 'critical and final failure parameters'. Each parameter in this model has been analysed in terms of various results in the literature. Both experimental and numerical results have been obtained for notched round and CT specimens to characterize ductile failure in a NiCr steel (12NC6) with a small initial void volume fraction f{sub 0} (f{sub 0}=0.001%). Ductile crack growth, defined by the J-{delta}a curve, has been correctly simulated using the numerical calculations by adjusting the different parameters of the GTN model in the calibration procedure.

  18. Gestational Trophoblastic Neoplasm and Women Living With HIV ...

    African Journals Online (AJOL)

    The overall cure rate is about 90%. Response to treatment for GTN is generally favourable; but the sequelae of HIV and/or AIDS, the resultant low CD4 counts, comorbidities, poor performance status and the extent of metastatic disease in patients receiving chemotherapy, compromise the prognosis and survival.

  19. Data Integration Tool: Permafrost Data Debugging

    Science.gov (United States)

    Wilcox, H.; Schaefer, K. M.; Jafarov, E. E.; Pulsifer, P. L.; Strawhacker, C.; Yarmey, L.; Basak, R.

    2017-12-01

    We developed a Data Integration Tool (DIT) to significantly speed up the time of manual processing needed to translate inconsistent, scattered historical permafrost data into files ready to ingest directly into the Global Terrestrial Network-Permafrost (GTN-P). The United States National Science Foundation funded this project through the National Snow and Ice Data Center (NSIDC) with the GTN-P to improve permafrost data access and discovery. We leverage this data to support science research and policy decisions. DIT is a workflow manager that divides data preparation and analysis into a series of steps or operations called widgets (https://github.com/PermaData/DIT). Each widget does a specific operation, such as read, multiply by a constant, sort, plot, and write data. DIT allows the user to select and order the widgets as desired to meet their specific needs, incrementally interact with and evolve the widget workflows, and save those workflows for reproducibility. Taking ideas from visual programming found in the art and design domain, debugging and iterative design principles from software engineering, and the scientific data processing and analysis power of Fortran and Python it was written for interactive, iterative data manipulation, quality control, processing, and analysis of inconsistent data in an easily installable application. DIT was used to completely translate one dataset (133 sites) that was successfully added to GTN-P, nearly translate three datasets (270 sites), and is scheduled to translate 10 more datasets ( 1000 sites) from the legacy inactive site data holdings of the Frozen Ground Data Center (FGDC). Iterative development has provided the permafrost and wider scientific community with an extendable tool designed specifically for the iterative process of translating unruly data.

  20. The prophylactic effect of valproate on glyceryltrinitrate induced migraine

    DEFF Research Database (Denmark)

    Tvedskov, Jesper Filtenborg; Thomsen, L L; Iversen, H K

    2004-01-01

    In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test valproate due to its well documented effect as a migraine prophylactic drug. Efficacy of this compound would support the usefulness of the mod...

  1. 77 FR 59608 - Gas Transmission Northwest LLC; Notice of Petition for Declaratory Order

    Science.gov (United States)

    2012-09-28

    ... Transmission Northwest LLC; Notice of Petition for Declaratory Order Take notice that on September 18, 2012... natural gas GTN transports on its system must be ``entirely free'' of compressor oil. Any person desiring... the appropriate link in the above list. They are also available for review in the Commission's Public...

  2. Thallium (III) salts utilization in organic synthesis. Part II

    International Nuclear Information System (INIS)

    Ferraz, H.M.C.

    1989-01-01

    The utilizations of thallium (III) salts in organic synthesis with carbonylic and acitylenic substrates are presented. The reactions of carbonylic substra3ts with kitones and the oxidation reactions of acetylenic substrates are shown. Others reactions including thallium (III) salts and non aromatic unsatured substracts, as cleasage of ethers and epoxide using thallium trinitrate, hydrazones treatments with thallium triacetates, etc, are also mentioned. (C.G.C.) [pt

  3. 21 CFR 172.811 - Glyceryl tristearate.

    Science.gov (United States)

    2010-04-01

    ... crystallization accelerator in cocoa products, in imitation chocolate, and in compound coatings Not to exceed 1... product that complies with the limitations prescribed in paragraph (c) of this section. [53 FR 21632, June...

  4. Modeling the damage of welded steel, using the GTN model

    Directory of Open Access Journals (Sweden)

    El-Ahmar Kadi

    2014-11-01

    Full Text Available The aim of our work is the modeling of the damage in the weld metal according to the finite element method and the concepts of fracture mechanics based on local approaches using the code ABAQUS calculates. The use of the Gurson-Tvergaard-Needleman model axisymmetric specimens AE type to three different zones (Base metal, molten metal and heat affected Zone with four levels of triaxiality (AE2, AE4, AE10 and AE80, we have used to model the behavior of damage to welded steel, which is described as being due to the growth and coalescence of cavities with high rates of triaxiality

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

    Directory of Open Access Journals (Sweden)

    Angélica Martínez-Hernández

    Full Text Available 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 (GTn 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 (GTn 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 (GTn 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.

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

    Directory of Open Access Journals (Sweden)

    Maria José Franco Brochado

    2016-02-01

    Full Text Available 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 [(GTn, 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 (GTn 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 (GTn polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

  7. Effects of microscale inertia on dynamic ductile crack growth

    Science.gov (United States)

    Jacques, N.; Mercier, S.; Molinari, A.

    2012-04-01

    The aim of this paper is to investigate the role of microscale inertia in dynamic ductile crack growth. A constitutive model for porous solids that accounts for dynamic effects due to void growth is proposed. The model has been implemented in a finite element code and simulations of crack growth in a notched bar and in an edge cracked specimen have been performed. Results are compared to predictions obtained via the Gurson-Tvergaard-Needleman (GTN) model where micro-inertia effects are not accounted for. It is found that microscale inertia has a significant influence on the crack growth. In particular, it is shown that micro-inertia plays an important role during the strain localisation process by impeding void growth. Therefore, the resulting damage accumulation occurs in a more progressive manner. For this reason, simulations based on the proposed modelling exhibit much less mesh sensitivity than those based on the viscoplastic GTN model. Microscale inertia is also found to lead to lower crack speeds. Effects of micro-inertia on fracture toughness are evaluated.

  8. Application of D-optimal experimental design method to optimize the formulation of O/W cosmetic emulsions.

    Science.gov (United States)

    Djuris, J; Vasiljevic, D; Jokic, S; Ibric, S

    2014-02-01

    This study investigates the application of D-optimal mixture experimental design in optimization of O/W cosmetic emulsions. Cetearyl glucoside was used as a natural, biodegradable non-ionic emulsifier in the relatively low concentration (1%), and the mixture of co-emulsifiers (stearic acid, cetyl alcohol, stearyl alcohol and glyceryl stearate) was used to stabilize the formulations. To determine the optimal composition of co-emulsifiers mixture, D-optimal mixture experimental design was used. Prepared emulsions were characterized with rheological measurements, centrifugation test, specific conductivity and pH value measurements. All prepared samples appeared as white and homogenous creams, except for one homogenous and viscous lotion co-stabilized by stearic acid alone. Centrifugation testing revealed some phase separation only in the case of sample co-stabilized using glyceryl stearate alone. The obtained pH values indicated that all samples expressed mild acid value acceptable for cosmetic preparations. Specific conductivity values are attributed to the multiple phases O/W emulsions with high percentages of fixed water. Results of the rheological measurements have shown that the investigated samples exhibited non-Newtonian thixotropic behaviour. To determine the influence of each of the co-emulsifiers on emulsions properties, the obtained results were evaluated by the means of statistical analysis (ANOVA test). On the basis of comparison of statistical parameters for each of the studied responses, mixture reduced quadratic model was selected over the linear model implying that interactions between co-emulsifiers play the significant role in overall influence of co-emulsifiers on emulsions properties. Glyceryl stearate was found to be the dominant co-emulsifier affecting emulsions properties. Interactions between the glyceryl stearate and other co-emulsifiers were also found to significantly influence emulsions properties. These findings are especially important

  9. 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

    OpenAIRE

    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 o...

  10. Isolation and identification of compounds from Phaleria macrocarpa (Scheff. Boerl fruit extract

    Directory of Open Access Journals (Sweden)

    Emanuel Dani Ramdani

    2017-04-01

    Conclusions: A new compound was isolated and identified as glyceryl pentacosanoate. Also, two xanthones, which are 1,7-dihydroxy-3,6-dimethoxyxanthone and 1,6,7-trihydroxy-3-methoxyxanthone, are firstly reported to be isolated from P. macrocarpa.

  11. Thallium trinitrate mediated ring contraction of cis-2-decalones

    Directory of Open Access Journals (Sweden)

    Ferraz Helena M. C.

    2001-01-01

    Full Text Available The reaction of some cis-2-decalones with TTN in CH2Cl2 at room temperature was investigated. The ring contraction reactions occurred in good yields, however the regio- and diastereoselectivity were low. The effect of the alkyl groups in the regiochemistry of the reaction depends on their position at the decalone ring system.

  12. Ductile failure analysis of high strength steel in hot forming based on micromechanical damage model

    OpenAIRE

    Ying Liang; Liu Wenquan; Wang Dantong; Hu Ping

    2016-01-01

    The damage evolution of high strength steel at elevated temperature is investigated by using the Gurson-Tvergaard-Needleman (GTN) model. A hybrid method integrated thermal tensile test and numerical technique is employed to identify the damage parameters. The analysis results show that the damage parameters are different at different temperature as the variation of tested material microstructure. Furthermore, the calibrated damage parameters are implemented to simulate a bugling forming at el...

  13. Semiconductor particle mediated photoelectron transfers in bilayer lipid membranes

    International Nuclear Information System (INIS)

    Fendler, J.H.; Baral, S.

    1989-01-01

    This paper discusses semiconductor particles in situ generated on the cis surface of glyceryl monooleate (GMO) bilayer lipid membranes (BLMs), that have been used to mediate photoelectric effects. The presence of semiconductors on the BLM surface is addressed. The observed photoelectric effects are rationalized and presented

  14. Nitroglycerin kan give hypertension

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

    Directory of Open Access Journals (Sweden)

    Kai Lee Yap

    2010-01-01

    Full Text Available Gestational trophoblastic neoplasms (GTNs are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs and epithelioid trophoblastic tumors (ETTs. Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10% of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5% of 19 choriocarcinomas, one (7% of 15 PSTTs and three (18% of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

  16. Sonographic image of cervix epithelioid trophoblastic tumor coexisting with mucinous adenocarcinoma in a postmenopausal woman: A case report.

    Science.gov (United States)

    Zhu, Yi; Zhang, Guo-Nan; Zhang, Rui-Bo; Shi, Yu; Wang, Deng-Feng; He, Rong

    2017-09-01

    Epithelioid trophoblastic tumor (ETT) is a distinctive but rare gestational trophoblastic neoplasia (GTN) composed of chorionic-type intermediate trophoblast cells. Approximately 50% ETT arose from the uterine cervix or lower uterine segment following a previous pregnancy with vaginal bleeding. With its unusual ability to simulate an invasive epithelioid neoplasm, ETT frequently poses a diagnostic challenge, especially involving the uterine cervix. We herein report the case of a 60-year-old female with persistent vaginal bleeding and middle-level elevation of serum human chorionic gonadotropin (hCG). Ultrasound revealed a 3.0 × 2.7 cm well-circumscribed, strongly echogenic lesion in the cervix, with a peripheral pattern of Doppler signals. The enhanced pattern by contrast-enhanced ultrasound displayed strong peripheral enhancement accompanied with globular appearance, then centripetal filling completely, and fading away rapidly. The final pathological diagnosis was ETT accompanying mucinous adenocarcinoma. Due to the pre-operative evaluation of a presumed IB2 cervix mucinous adenocarcinoma, the patient was treated with 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy. The patient is currently disease-free for the past 1 year. This case report demonstrates that sonographic image of tumor shapes and blood flow could be helpful in differentiating ETT from another GTN and enable more accurate diagnosis before treatment.

  17. The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles

    DEFF Research Database (Denmark)

    Liu, Jingying; Christophersen, Philip C; Yang, Mingshi

    2017-01-01

    OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM. METHODS: Labeled lysozyme was incorporated...... provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.......OBJECTIVE: The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM. METHODS: Labeled lysozyme was incorporated...... into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser...

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

    Science.gov (United States)

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

    2017-07-14

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

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

    Directory of Open Access Journals (Sweden)

    Guillaume Brault

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

  20. Structural determination of individual chemical species in a mixed system by iterative transformation factor analysis-based X-ray absorption spectroscopy combined with UV-visible absorption and quantum chemical calculation.

    Science.gov (United States)

    Ikeda, Atsushi; Hennig, Christoph; Rossberg, André; Tsushima, Satoru; Scheinost, Andreas C; Bernhard, Gert

    2008-02-15

    A multitechnique approach using extended X-ray absorption fine structure (EXAFS) spectroscopy based on iterative transformation factor analysis (ITFA), UV-visible absorption spectroscopy, and density functional theory (DFT) calculations has been performed in order to investigate the speciation of uranium(VI) nitrate species in acetonitrile and to identify the complex structure of individual species in the system. UV-visible spectral titration suggests that there are four different species in the system, that is, pure solvated species, mono-, di-, and trinitrate species. The pure EXAFS spectra of these individual species are extracted by ITFA from the measured spectral mixtures on the basis of the speciation distribution profile calculated from the UV-visible data. Data analysis of the extracted EXAFS spectra, with the help of DFT calculations, reveals the most probable complex structures of the individual species. The pure solvated species corresponds to a uranyl hydrate complex with an equatorial coordination number (CNeq) of 5, [UO2(H2O)5]2+. Nitrate ions tend to coordinate to the uranyl(VI) ion in a bidentate fashion rather than a unidentate one in acetonitrile for all the nitrate species. The mononitrate species forms the complex of [UO2(H2O)3NO3]+ with a CNeq value of 5, while the di- and trinitrate species have a CNeq value of 6, corresponding to [UO2(H2O)2(NO3)2]0 (D2h) and [UO2(NO3)3]- (D3h), respectively.

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

    Science.gov (United States)

    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. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K

    1993-01-01

    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...... 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....

  3. Treatment of Acute Fissure in Ano using Topical Glycerine Trinitrate ...

    African Journals Online (AJOL)

    RICHY

    longitudinal tear of the lower anal canal. It is one of the painful anal conditions resulting in a lot of ... constipation, doing so with a fresh tear more likely during next defecation. The aetiology varies from precipitous ... increases NO (nitric oxide) which is a very potent muscle relaxant. It acts on vascular smooth muscle there by.

  4. Failure analysis based on microvoid growth for sheet metal during uniaxial and biaxial tensile tests

    International Nuclear Information System (INIS)

    Abbassi, Fethi; Mistou, Sebastien; Zghal, Ali

    2013-01-01

    Highlights: ► Cruciform specimen designed and biaxial tensile test carried out. ► Stereo Correlation Image technique is used for 3D full-filed measurements. ► SEM fractography analysis is used to explain the fracture mechanism. ► Constitutive modeling of the necking phenomenon was developed using GTN model. - Abstract: The aim of the presented investigations is to perform an analysis of fracture and instability during simple and complex load testing by addressing the influence of ductile damage evolution in necking processes. In this context, an improved experimental methodology was developed and successfully used to evaluate localization of deformation during uniaxial and biaxial tensile tests. The biaxial tensile tests are carried out using cruciform specimen loaded using a biaxial testing machine. In this experimental investigation, Stereo-Image Correlation technique has is used to produce the heterogeneous deformations map within the specimen surface. Scanning electron microscope is used to evaluate the fracture mechanism and the micro-voids growth. A finite element model of uniaxial and biaxial tensile tests are developed, where a ductile damage model Gurson–Tvergaard–Needleman (GTN) is used to describe material deformation involving damage evolution. Comparison between the experimental and the simulation results show the accuracy of the finite element model to predict the instability phenomenon. The advanced measurement techniques contribute to understand better the ductile fracture mechanism

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

    Science.gov (United States)

    Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L; Braad, Poul Erik; Petersen, Henrik; Høilund-Carlsen, Poul Flemming; Bie, Peter

    2010-12-01

    The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor N(ω)-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.

  6. Problem Definition Studies on Potential Environmental Pollutants. V. Physical, Chemical, Toxicological, and Biological Properties of Seven Chemicals used in Pyrotechnic Compositions

    Science.gov (United States)

    1979-10-01

    nfested 7 by parasi~tir worms, in particular the Liver fl~, Fasciola hspatca an-d the stomach worm. Ham-onchus :ontnr-11m.6 In .tcstude bY mack;: r a...subcutan.e- ’)IQy imp]lanted adult Fasciola in ia-as. 78Hexachloroethane is ineffective .’gtn1st the smiall tiukeworme, Dicrocoeliose ovinle, and some other...60. Olsen, O.W., "Hexachlorcethane-Bentonite Suspension for Controlling the Common Liver Fluke, Fasciola hepatica, in Cattle in the Gulf Coast Region

  7. Identification of microsatellite DNA markers for the giant anteater Myrmecophaga tridactyla.

    Science.gov (United States)

    Garcia, J E; Vilas Boas, L A; Lemos, M V F; de Macedo Lemos, E G; Contel, E P B

    2005-01-01

    The giant anteater (Myrmecophaga tridactyla) is found from Belize and Guatemala to Paraguay and Argentina. Its conservation status is considered vulnerable by IUCN. Here we report the isolation and characterization of six microsatellite loci. Positive loci for (GT)(n) were isolated using a magnetic bead hybridization selection protocol. The number of alleles per locus as well as the heterozygosity and PCR conditions are described. These loci will be useful for studying population structure, genetic diversity, and paternity in M. tridactyla wild populations.

  8. Cyclization of lapachol induced by thallium salts

    International Nuclear Information System (INIS)

    Ribeiro, Carlos Magno R.; Souza, Pablo P. de; Ferreira, Leticia L.D.M.; Pinto, Lia A.; Almeida, Leonardo S. de; Jesus, Janaina G. de

    2008-01-01

    This work describes the cyclization of lapachol (1) induced by thallium triacetate (TTA) and thallium trinitrate (TTN) in several solvents using magnetic stirring and under microwave irradiation. α-Xyloidone (2) - dehydro-a-lapachone - was obtained as the main product in these reactions in 20 - 75% yield. However, rhinacanthin-A (4) was isolated as main product in a 40% yield, using TTA and acetic anhydride:water (1:1) as solvent, and dehydroiso- a-lapachone (3) in 21% yield, using TTA and dichloromethane as solvent. The reaction time decreased drastically under microwave conditions, but the yields of these reactions were not the expected. (author)

  9. Polymorphisms in the Haem Oxygenase-1 promoter are not associated with severity of Plasmodium falciparum malaria in Ghanaian children.

    Science.gov (United States)

    Hansson, Helle H; Maretty, Lasse; Balle, Christina; Goka, Bamenla Q; Luzon, Elisa; Nkrumah, Francis N; Schousboe, Mette L; Rodrigues, Onike P; Bygbjerg, Ib Christian; Kurtzhals, Jørgen A L; Alifrangis, Michael; Hempel, Casper

    2015-04-11

    Haem oxygenase-1 (HO-1) catabolizes haem and has both cytotoxic and cytoprotective effects. Polymorphisms in the promoter of the Haem oxygenase-1 (HMOX1) gene encoding HO-1 have been associated with several diseases including severe malaria. The objective of this study was to determine the allele and genotype frequencies of two single nucleotide polymorphisms; A(-413)T and G(-1135)A, and a (GT)n repeat length polymorphism in the HMOX1 promoter in paediatric malaria patients and controls to determine possible associations with malaria disease severity. Study participants were Ghanaian children (n=296) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as having uncomplicated malaria (n=101) or severe malaria (n=195; defined as severe anaemia (n=63) or cerebral malaria (n=132)). Furthermore, 287 individuals without a detectable Plasmodium infection or asymptomatic carriers of the parasite were enrolled as controls. Blood samples from participants were extracted for DNA and allele and genotype frequencies were determined with allele-specific PCR, restriction fragment length analysis and microsatellite analysis. The number of (GT)n repeats in the study participants varied between 21 and 46 with the majority of alleles having lengths of 26 (8.1%), 29/30 (13.2/17.9%) and 39/40 (8.0/13.8%) repeats, and was categorized into short, medium and long repeats. The (-413)T allele was very common (69.8%), while the (-1135)A allele was present in only 17.4% of the Ghanaian population. The G(-1135)A locus was excluded from further analysis after failing the Hardy-Weinberg equilibrium test. No significant differences in allele or genotype distribution of the A(-413)T and (GT)n repeat polymorphisms were found between the controls and the malaria patients, or between the disease groups, for any of the analysed polymorphisms and no associations with

  10. A study of local deformation and damage of dual phase steel

    International Nuclear Information System (INIS)

    Sirinakorn, T.; Wongwises, S.; Uthaisangsuk, V.

    2014-01-01

    Highlights: • Crack initiation in DP microstructure was investigated using 2D RVE simulation. • The GTN damage model was used to describe void evolution in ferrite and interphase. • Predicted damage at triple junctions agreed with observed crack initiation sites. • RVE with GNDs zone showed damages took place at earlier deformation state. • Overall loading condition exhibited significant effect on damage evolution rate. - Abstract: Deformation and fracture behavior of Dual Phase (DP) high strength steel were investigated by means of a microstructure based Finite Element (FE) modeling. Representative Volume Elements (RVEs) were applied to consider effects of various microstructure constituents and characteristics. Individual stress–strain curves were provided for ferrite, martensite as well as transformation induced Geometrically Necessary Dislocations (GNDs) taking into account in the RVEs. Principally, the GNDs occurred around phase boundaries during quenching process due to the austenite–martensite transformation. Flow behaviors of individual phases were defined on the basis of dislocation theory and partitioning of local chemical composition. Then, flow curves of the examined DP steel were predicted. Furthermore, the Gurson–Tvergaard–Needleman (GTN) model was used to represent ductile damage evolution in the microstructure. Occurrences of void initiation were characterized and damage parameters for RVE simulations were hence identified. Finally, influences of the GNDs, local stress and strain distributions and interactions between phases on predicted crack initiation in the DP microstructure were discussed and correlated with experimental results

  11. Impacts of a Course-based Undergraduate Research Experience in Introductory Astronomy Using Robotic Telescopes

    Science.gov (United States)

    Dobaria, Archana S.; Coble, Kimberly A.; Alejandra, Le; Berryhill, Katie; McLin, Kevin M.; Cominsky, Lynn R.

    2018-06-01

    As part of a general education undergraduate astronomy course at a minority-serving university in the Midwestern US, students completed an observing project with the Global Telescope Network (GTN), where they participated in realistic practices used by professional astronomers, including proposal writing and peer review. First, students went through the process of applying for telescope time by choosing an astronomical object and writing an observing proposal. Then they performed an NSF-style review of classmates’ proposals, including written peer reviews and a review panel. After obtaining images from GTN telescopes, students presented their project and findings in front of the class.This study investigates students’ experiences and perceived impacts of participation in the project. The data analyzed includes an essay assignment [N = 59] administered over seven semesters and individual interviews [N = 8] collected over two semesters. Students were prompted to address what they liked, disliked, or would change about the project experience. These data were coded iteratively into nine categories. A Kruskal-Wallis (KW) test was used to determine that essay results from different semesters could be combined. We find that students expressed an overall strong positive affect, increased perception of self-efficacy, enjoyment of the experience of peer review, an appreciation for being able to use real scientific tools and to take on the role of astronomers, as well as a small number of dislikes such as real-world constraints on observing.

  12. Predicting failure response of spot welded joints using recent extensions to the Gurson model

    DEFF Research Database (Denmark)

    Nielsen, Kim Lau

    2010-01-01

    The plug failure modes of resistance spot welded shear-lab and cross-tension test specimens are studied, using recent extensions to the Gurson model. A comparison of the predicted mechanical response is presented when using either: (i) the Gurson-Tvergaard-Needleman model (GTN-model), (ii...... is presented. The models are applied to predict failure of specimens containing a fully intact weld nugget as well as a partly removed weld nugget to address the problems of shrinkage voids or larger weld defects. All analysis are carried out by full 3D finite element modelling....

  13. Phase 2 Comparison of A Novel Ammonia Scavenging Agent With Sodium Phenylbutyrate In Patients With Urea Cycle Disorders: Safety, Pharmacokinetics And Ammonia Control

    OpenAIRE

    Lee, Brendan; Rhead, William; Diaz, George A.; Scharschmidt, Bruce F.; Mian, Asad; Shchelochkov, Oleg; Marier, JF; Beliveau, Martin; Mauney, Joseph; Dickinson, Klara; Martinez, Antonia; Gargosky, Sharron; Mokhtarani, Masoud; Berry, Susan A.

    2010-01-01

    Glycerol phenylbutyrate (glyceryl tri (4-phenylbutyrate)) (GPB) is being studied as an alternative to sodium phenylbutyrate (NaPBA) for the treatment of urea cycle disorders (UCDs). This phase 2 study explored the hypothesis that GPB offers similar safety and ammonia control as NaPBA, which is currently approved as adjunctive therapy in the chronic management of UCDs, and examined correlates of 24-hour blood ammonia.

  14. A radiotracer technique for testing a high pressure gas compressor for oil leakage

    International Nuclear Information System (INIS)

    Eapen, A.C.; Kirti; Jain, S.K.; Gupta, P.P.

    1979-01-01

    The radiotracer investigations carried out at NOCIL, Bombay, to measure the amount of lubrication oil present in the gas being compressed in a 1000 H.P. centrifugal compressor are described. By injecting a few mCi 131 I labelled glyceryl trioleate tracer and monitoring the radioactivity of the outlet gas for about 20 hours, the extent of the oil present in the gas could be determined. (auth.)

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

    Science.gov (United States)

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

    2012-01-01

    To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® Once™, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™. PMID:22923986

  16. Ciclização do lapachol induzida por sais de tálio III Cyclyzation of lapachol induced by thallium salts

    Directory of Open Access Journals (Sweden)

    Carlos Magno R. Ribeiro

    2008-01-01

    Full Text Available This work describes the cyclization of lapachol (1 induced by thallium triacetate (TTA and thallium trinitrate (TTN in several solvents using magnetic stirring and under microwave irradiation. alpha-Xyloidone (2 - dehydro-alpha-lapachone - was obtained as the main product in these reactions in 20 75% yield. However, rhinacanthin-A (4 was isolated as main product in a 40% yield, using TTA and acetic anhydride:water (1:1 as solvent, and dehydro-iso-alpha-lapachone (3 in 21% yield, using TTA and dichloromethane as solvent. The reaction time decreased drastically under microwave conditions, but the yields of these reactions were not the expected.

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

    Directory of Open Access Journals (Sweden)

    Stefano La Tegola

    2013-01-01

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

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

    OpenAIRE

    La Tegola, Stefano; Annese, Cosimo; Suman, Michele; Tommasi, Immacolata; Fusco, Caterina; D'Accolti, Lucia

    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.

  19. Direct synthesis of ESBO derivatives-¹⁸O labelled with dioxirane.

    Science.gov (United States)

    La Tegola, Stefano; Annese, Cosimo; Suman, Michele; Tommasi, Immacolata; Fusco, Caterina; D'Accolti, Lucia

    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.

  20. Endothelial function in male body builders taking anabolic androgenic steroids

    Directory of Open Access Journals (Sweden)

    H Hashemi

    2005-11-01

    Full Text Available Background: Adverse cardiovascular events have been reported in body builders taking anabolic steroids. Adverse effects of AAS on endothelial function can initiate atherosclerosis. This study evaluates endothelial function in body builders using AAS, compared with non-steroids using athletes as controls. Methods: We recruited 30 nonsmoking male body builders taking AAS, 14 in build up phase, 8 in work out phase, and 8 in post steroid phase, and 30 nonsmoking male athletes who denied ever using steroids. Serum lipids and fasting plasma glucose were measured to exclude dyslipidemia and diabetes. Brachial artery diameter was measured by ultrasound at rest, after cuff inflation, and after sublingual glyceriltrinitrate (GTN to determine flow mediated dilation (FMD, nitro mediated dilation (NMD and ratio of FMD to NMD (index of endothelial function. Result: Use of AAS was associated with higher body mass index (BMI and low density lipoprotein–cholesterol (LDL-C. Mean ratio of flow mediated dilatation after cuff deflation to post GTN dilatation of brachial artery (index of endothelial function in body builders taking AAS was significantly lower than control group (0.96(0.05 versus 1(0.08; p=0.03. After adjusting BMI, age and weight, no significant difference was seen in index of endothelial function between two groups (p=0 .21. Conclusion: Our study indicates that taking AAS in body builders doesn’t have direct effect on endothelial function. Future study with bigger sample size and measurement of AAS metabolites is recommended. Key words: endothelium, lipids, anabolic steroids, body builders

  1. Structural transformations and temperature state of rotating blades of E1893 alloy under operation

    Energy Technology Data Exchange (ETDEWEB)

    Pigrova, G D; Rybnikov, A I; Kryukov, I I [Polzunov Central Boiler and Turbine Institute, St. Petersburg (Russian Federation)

    1999-12-31

    The composition and quantity of different phase component of EI893 alloy after long term operation as base metal for rotating blades of gas turbines GT-6, GTN-9, GTK-10 and GT-100 types were studied. The obtained date were analysed with regard to the chemical composition of alloys and of initial condition of heat treatment. Data of metal phase analysis owned alter operation can provide the basis for evaluation of tempera field of rotating blades in the course of operation since structural condition of phase components and redistribution of alloying elements are being specified by temperature and in-service time. (orig.)

  2. Structural transformations and temperature state of rotating blades of E1893 alloy under operation

    Energy Technology Data Exchange (ETDEWEB)

    Pigrova, G.D.; Rybnikov, A.I.; Kryukov, I.I. [Polzunov Central Boiler and Turbine Institute, St. Petersburg (Russian Federation)

    1998-12-31

    The composition and quantity of different phase component of EI893 alloy after long term operation as base metal for rotating blades of gas turbines GT-6, GTN-9, GTK-10 and GT-100 types were studied. The obtained date were analysed with regard to the chemical composition of alloys and of initial condition of heat treatment. Data of metal phase analysis owned alter operation can provide the basis for evaluation of tempera field of rotating blades in the course of operation since structural condition of phase components and redistribution of alloying elements are being specified by temperature and in-service time. (orig.)

  3. Lipid metabolites with free-radical scavenging activity from Euphorbia helioscopia L.

    Science.gov (United States)

    Cateni, F; Zilic, J; Altieri, T; Zacchigna, M; Procida, G; Gaggeri, R; Rossi, D; Collina, S

    2014-07-01

    The methanolic extract of the plant Euphorbia helioscopia L. exhibited an interesting free-radical scavenging activity. From the aerial parts of Euphorbia helioscopia L. (Euphorbiaceae), a complex mixture of seven cerebrosides together with glucoclionasterol, a digalactosyldiacylglycerol and a diacylmonogalactosylglycerol were identified. The structures of the cerebrosides were characterized as 1-O-β-D-glucosides of phytosphingosines, which comprised (2S, 3S, 4E, 8E)-2-amino-4(E),8(E)-octadecadiene-1,3-diol, (2S, 3S, 4E, 8Z)-2-amino-4(E),8(Z)-octadecadiene-1,3-diol, (2S, 3S, 4R, 8Z)-2-amino-8(Z)-octadecene-1,3,4-triol as long chain bases with seven 2-hydroxy fatty acids of varying chain lengths (C16, C24:1, C26:1, C24, C26, C28:1) linked to the amino group. The glycosylglycerides were characterized as (2S)-2,3-O-di-(9,12,15-octadecatrienoyl)-glyceryl-6-O-(α-D-galactopyranosyl)-β-D-galactopyranoside and (2S)-2,3-O-di-(9,12,15-octadecatrienoyl)-glyceryl-1-O-β-D-galactopyranoside. The structures were established on the basis of spectroscopic data and chemical reactions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Nitroglycerine and sodium trioxodinitrate: from the discovery to the preconditioning effect.

    Science.gov (United States)

    Pagliaro, Pasquale; Gattullo, Donatella; Penna, Claudia

    2013-10-01

    The history began in the 19th century with Ascanio Sobrero (1812-1888), the discoverer of glycerol trinitrate (nitroglycerine, NTG), and with Angelo Angeli (1864-1931), the discoverer of sodium trioxodinitrate (Angeli's salt). It is likely that Angeli and Sobrero never met, but their two histories will join each other more than a century later. In fact, it has been discovered that both NTG and Angeli's salt are able to induce a preconditioning effect. As NTG has a long history as an antianginal drug its newly discovered property as a preconditioning agent has also been tested in humans. Angeli's salt properties as a preconditioning and inotropic agent have only been tested in animals so far.

  5. Development and evaluation of exemestane-loaded lyotropic liquid crystalline gel formulations

    OpenAIRE

    Musa, Muhammad Nuh; David, Sheba Rani; Zulkipli, Ihsan Nazurah; Mahadi, Abdul Hanif; Chakravarthi, Srikumar; Rajabalaya, Rajan

    2017-01-01

    Introduction: The use of liquid crystalline (LC) gel formulations for drug delivery has considerably improved the current delivery methods in terms of bioavailability and efficacy. The purpose of this study was to develop and evaluate LC gel formulations to deliver the anti-cancer drug exemestane through transdermal route. Methods: Two LC gel formulations were prepared by phase separation coacervation method using glyceryl monooleate (GMO), Tween 80 and Pluronic® F127 (F127). The formulations...

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

    Science.gov (United States)

    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

  7. Glacier Monitoring and Capacity Building: Important Ingredients for Sustainable Mountain Development

    Directory of Open Access Journals (Sweden)

    Samuel U. Nussbaumer

    2017-02-01

    Full Text Available Glacier observation data from major mountain regions of the world are key to improving our understanding of glacier changes: they deliver fundamental baseline information for climatological, hydrological, and hazard assessments. In many mountain ecosystems, as well as in the adjacent lowlands, glaciers play a crucial role in freshwater provision and regulation. This article first presents the state of the art on glacier monitoring and related strategies within the framework of the Global Terrestrial Network for Glaciers (GTN-G. Both in situ measurements of changes in glacier mass, volume, and length as well as remotely sensed data on glacier extents and changes over entire mountain ranges provide clear indications of climate change. Based on experiences from capacity-building activities undertaken in the Tropical Andes and Central Asia over the past years, we also review the state of the art on institutional capacity in these regions and make further recommendations for sustainable mountain development. The examples from Peru, Ecuador, Colombia, and Kyrgyzstan demonstrate that a sound understanding of measurement techniques and of the purpose of measurements is necessary for successful glacier monitoring. In addition, establishing durable institutions, capacity-building programs, and related funding is necessary to ensure that glacier monitoring is sustainable and maintained in the long term. Therefore, strengthening regional cooperation, collaborating with local scientists and institutions, and enhancing knowledge sharing and dialogue are envisaged within the GTN-G. Finally, glacier monitoring enhances the resilience of the populations that depend on water resources from glacierized mountains or that are affected by hazards related to glacier changes. We therefore suggest that glacier monitoring be included in the development of sustainable adaptation strategies in regions with glaciated mountains.

  8. An investigative study into psychological and fertility sequelae of gestational trophoblastic disease: the impact on patients' perceived fertility, anxiety and depression.

    Directory of Open Access Journals (Sweden)

    Valentina E Di Mattei

    Full Text Available 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.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.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.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.

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

    Science.gov (United States)

    Daiber, Andreas; Münzel, Thomas

    2015-10-10

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

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

    Science.gov (United States)

    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

  11. A modified Gurson-type plasticity model at finite strains: formulation, numerical analysis and phase-field coupling

    Science.gov (United States)

    Aldakheel, Fadi; Wriggers, Peter; Miehe, Christian

    2017-12-01

    The modeling of failure in ductile materials must account for complex phenomena at the micro-scale, such as nucleation, growth and coalescence of micro-voids, as well as the final rupture at the macro-scale, as rooted in the work of Gurson (J Eng Mater Technol 99:2-15, 1977). Within a top-down viewpoint, this can be achieved by the combination of a micro-structure-informed elastic-plastic model for a porous medium with a concept for the modeling of macroscopic crack discontinuities. The modeling of macroscopic cracks can be achieved in a convenient way by recently developed continuum phase field approaches to fracture, which are based on the regularization of sharp crack discontinuities, see Miehe et al. (Comput Methods Appl Mech Eng 294:486-522, 2015). This avoids the use of complex discretization methods for crack discontinuities, and can account for complex crack patterns. In this work, we develop a new theoretical and computational framework for the phase field modeling of ductile fracture in conventional elastic-plastic solids under finite strain deformation. It combines modified structures of Gurson-Tvergaard-Needelman GTN-type plasticity model outlined in Tvergaard and Needleman (Acta Metall 32:157-169, 1984) and Nahshon and Hutchinson (Eur J Mech A Solids 27:1-17, 2008) with a new evolution equation for the crack phase field. An important aspect of this work is the development of a robust Explicit-Implicit numerical integration scheme for the highly nonlinear rate equations of the enhanced GTN model, resulting with a low computational cost strategy. The performance of the formulation is underlined by means of some representative examples, including the development of the experimentally observed cup-cone failure mechanism.

  12. Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: systematic review and meta-analysis.

    Science.gov (United States)

    Archer, N S; Nassif, N T; O'Brien, B A

    2015-06-01

    A systematic review and meta-analyses were undertaken to investigate the association of SLC11A1 genetic variants with disease occurrence. Literature searching indentified 109 publications to include in the meta-analyses assessing the association of 11 SLC11A1 variants with autoimmune and infectious disease. The (GT)n promoter alleles 2 and 3 (rs534448891), which alter SLC11A1 expression, were significantly associated with tuberculosis (OR=1.47 (1.30-1.66), OR=0.76 (0.65-0.89), respectively) and infectious disease (OR=1.25 (1.10-1.42), OR=0.83 (0.74-0.93), respectively). However, although no association was observed with autoimmune disease, a modest significant association was observed with type 1 diabetes (allele 2 OR=0.94 (0.89-0.98)). On the basis of a stronger association of (GT)n allele 2 with tuberculosis, compared with the protective effect of allele 3, we hypothesise that allele 2 is likely the disease-causing variant influencing disease susceptibility. Significant associations were observed between the 469+14G/C polymorphism (rs3731865) and autoimmune disease (OR=1.30 (1.04-1.64)) and rheumatoid arthritis (OR=1.60 (1.20-2.13)) and between the -237C/T polymorphism (rs7573065) and inflammatory bowel disease (OR=0.60 (0.43-0.84)). Further, significant associations were identified between the 469+14G/C, 1730G/A and 1729+55del4 polymorphisms (rs3731865, rs17235409 and rs17235416, respectively) and both infectious disease per se and tuberculosis. These findings show a clear association between variants in the SLC11A1 locus and autoimmune and infectious disease susceptibility.

  13. Detection of triglyceride using an iridium nano-particle catalyst based amperometric biosensor.

    Science.gov (United States)

    Liao, Wei-Yin; Liu, Chung-Chiun; Chou, Tse-Chuan

    2008-12-01

    The detection and quantification of triglyceride (TG) using an iridium nano-particle modified carbon based biosensor was successfully carried out in this study. The detection procedures were based on the electrochemical detection of enzymatically produced NADH. TG was hydrolyzed by lipase and the glycerol produced was catalytically oxidized by NAD-dependent glycerol dehydrogenase producing NADH in a solution containing NAD(+). Glyceryl tributyrate, a short chain triglyceride, was chosen as the substrate for the evaluation of this TG biosensor in bovine serum and human serum. A linear response to glyceryl tributyrate in the concentration range of 0 to 10 mM and a sensitivity of 7.5 nA mM(-1) in bovine serum and 7.0 nA mM(-1) in human serum were observed experimentally. The potential interference of species such as uric acid (UA) and ascorbic acid (AA) was assessed. The incorporation of a selected surfactant and an increase in the incubation temperature appeared to enhance the performance of this biosensor. The conditions for the determination of TG levels in bovine serum using this biosensor were optimized, with sunflower seed oil being used as an analyte to simulate the detection of TG in blood. The experimental results demonstrated that this iridium nano-particle modified working electrode based biosensor provided a relatively simple means for the accurate determination of TG in serum.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Antioxidant phenolic compounds isolated from wild Pyrus ussuriensis Maxim. fruit peels and leaves.

    Science.gov (United States)

    Qiu, Daren; Guo, Jie; Yu, Huimei; Yan, Jiao; Yang, Shengxiang; Li, Xiang; Zhang, Yamei; Sun, Jinzhu; Cong, Jie; He, Shuliang; Wei, Dongsheng; Qin, Jian-Chun

    2018-02-15

    Thirteen phenolic compounds were isolated from pear (Pyrus ussuriensis Maxim.) peels and leaves extracts by using various column chromatography techniques with a guided DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging assay, the result of antioxidant activity of phenolic compounds is then verified by measurement of ROS (reactive oxygen species). The isolated compounds were identified as rutin (1), (-)-catechin (2), orobol (3), daidzein (4), tricin 4'-O-[threo-β-guaiacyl-(7″-O-methyl)-glyceryl] ether (5), tricin 4'-O-[threo-β-guaiacyl-(7″-O-methyl-9″-O-acetyl)-glyceryl] ether (6), 5,7,3',5'-tetrahydroxyflavanone (7), artselaeroside A (8), trilobatin (9), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (10), quercetin-3-O-(3″-O-galloyl)-α-l-rhamnopyranoside (11), apigenin (12) and quercetin (13) on the basis of nuclear magnetic resonance spectroscopy along with comparison with literature data. Among these compounds, quercetin and quercetin-3-O-(3″-O-galloyl)-α-l-rhamnopyranoside exhibited potent DPPH radical-scavenging activity with IC 50 (Half Maximal Inhibitory Concentration) value of 6.06 and 9.60μg/mL, respectively. The results revealed that P. ussuriensis could be used in the fields of food and medicine to prevent human aging diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A mucoadhesive in situ gel delivery system for paclitaxel

    OpenAIRE

    Jauhari, Saurabh; Dash, Alekha K.

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at d...

  17. Development of Numerical Analysis Techniques Based on Damage Mechanics and Fracture Mechanics

    International Nuclear Information System (INIS)

    Chang, Yoon Suk; Lee, Dock Jin; Choi, Shin Beom; Kim, Sun Hye; Cho, Doo Ho; Lee, Hyun Boo

    2010-04-01

    The scatter of measured fracture toughness data and transferability problems among different crack configurations as well as geometry and loading conditions are major obstacles for application of fracture mechanics. To address these issues, recently, concerns on the local approach employing reliable micro-mechanical damage models are being increased again in connection with a progress of computational technology. In the present research, as part of development of fracture mechanical evaluation model for material degradation of reactor pressure boundary, several investigations on fracture behaviors were carried out. Especially, a numerical scheme to determine key parameters consisting both cleavage and ductile fracture estimate models was changed efficiently by incorporating a genetic algorithm. Also, with regard to the well-known master curve, newly reported methods such as bimodal master curve, randomly inhomogeneous master curve and single point estimation were reviewed to deal with homogeneous and inhomogeneous material characteristics. A series of preliminary finite element analyses was conducted to examine the element size effect on micro-mechanical models. Then, a new thickness correction equation was derived from parametric three-dimensional numerical simulations, which was founded on the current test standard, ASTM E1921, but could lead to get more realistic fracture toughness values. As a result, promising modified master curves as well as fracture toughness diagrams to convert data between pre-cracked V-notched and compact tension specimens were generated. Moreover, a user-subroutine in relation to GTN(Gurson-Tvergaard-Needleman) model was made by adopting Hill's 48 yield potential theory. By applying GTN model combined with the subroutine to small punch specimens, the effect of inhomogeneous properties on fracture behaviors of miniature specimens was confirmed. Therefore, it is anticipated that the aforementioned enhanced research results can be utilized

  18. Evaluation of Candidate Anti-Aids Drugs In Vitro

    Science.gov (United States)

    1991-05-31

    numba by 50% (ED5) was calulatad using a regression aa-ysis program for semi-log curve fit’tig and was exnpresed a* ."g/Tn- The eapic index ,) wa dvte b y...czztairng 1.25 pg of poly (rA). p(c!T)12.11, 200 pM d= (400 kLCi of •’H,’•nle of ’- dT’P). 1mM S apo-rne•’ý • ol, 120 mM KCI, 0.6 mM MnC½, 0. 10 mM EDTA...Appendix B). The Mrst aýtive compounds (i.e. confirrnme activity with Selectivity Index (SI) of >10) are listed in Table !. During our overall experience

  19. Abiotic condensation synthesis of glyceride lipids and wax esters under simulated hydrothermal conditions.

    Science.gov (United States)

    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 ( composite function)C to 300 ( composite function)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 ( composite function)C and 250 ( composite function)C, and were detectable and thus stable under hydrothermal conditions to temperatures acid and glycerol were heated using the same experimental conditions, with and without oxalic acid, between 100 ( composite function)C and 250 ( composite function)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.

  20. Reconstructing 20th century global hydrography: a contribution to the Global Terrestrial Network- Hydrology (GTN-H

    Directory of Open Access Journals (Sweden)

    D. Wisser

    2010-01-01

    Full Text Available This paper presents a new reconstruction of the 20th century global hydrography using fully coupled water balance and transport model in a flexible modeling framework. The modeling framework allows a high level of configurability both in terms of input forcings and model structure. Spatial and temporal trends in hydrological cycle components are assessed under "pre-industrial" conditions (without modern-day human activities and contemporary conditions (incorporating the effects of irrigation and reservoir operations. The two sets of simulations allow the isolation of the trends arising from variations in the climate input driver alone and from human interventions. The sensitivity of the results to variations in input data was tested by using three global gridded datasets of precipitation.

    Our findings confirm that the expansion of irrigation and the construction of reservoirs has significantly and gradually impacted hydrological components in individual river basins. Variations in the volume of water entering the oceans annually, however, are governed primarily by variations in the climate signal alone with human activities playing a minor role. Globally, we do not find a significant trend in the terrestrial discharge over the last century.

    The largest impact of human intervention on the hydrological cycle arises from the operation of reservoirs that drastically changes the seasonal pattern of horizontal water transport in the river system and thereby directly and indirectly affects a number of processes such as ability to decompose organic matter or the cycling of nutrients in the river system.

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

    Science.gov (United States)

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

    2017-09-11

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

  2. Experimental determination of alpha particle threshold detection in cellulose nitrate

    International Nuclear Information System (INIS)

    Knoefell, T.M.J.

    1978-01-01

    LR 115, type II, Kodak-Pathe cellulose nitrate pellicles were irradiated perpendicularly with monoenergetic alpha bemas in the energy range 2,5-5,5 Mev. The alpha particle beams were produced by an intense Am 241 source using Argon as energy attenuating. After irradiations, samples were etched with NaOH solutions without agitation at 60 0 C, by different time periods varying from 15 minutes to 3,5 hours. Measurements of density and track diameter were done using optical microscopy. The sample compositions were done by CHN method of combustion gas analysis showing good agreement with the composition of cellulose trinitrate. From detection threshold and from obtained results, the development of latent tracks only occur for alpha particles with stopping power superior to 0,87 +- 0,06 MeV.cm -2 .mg -1 , was verified. (M.C.K.) [pt

  3. Incorporation of [U-14C] acetate into the lipids of scale insect, icerya purchasi maskell (Hemiptera: Margarodidae)

    International Nuclear Information System (INIS)

    Hashimoto, Akira; Kitaoka, Shozaburo.

    1979-01-01

    Incorporation of ( U- 14 C ) acetate into the lipids of scale insect Icerya purchasi was investigated. The insects were placed on a Parafilm membrane over a liquid food containing the labelled compound and allowed to suck up the liquid through the stylet piercing the membrane in the dark. The marker was incorporated into individual lipid classes, and after 1 hour of feeding the relative radioactivities of the classes were as follows: phospholipids gt (s)-3-acetyl-1,2-diacylglycerols (ADG) gt free fatty acids asymptotically equals diacylglycerols gt normal triacylglycerols (n-TG) gt monoacylglycerols. The ADG was fractionated into acetyl, diacyl and glyceryl moieties to determine the distribution of radioactivity within ADG. The acetyl moiety from the 3-position of sn-glycerol contained a higher percentage of radioactivity than any of other moieties. However, by feeding for 3 to 12 hours, the radioactivity was higher in the diacyl and glyceryl moieties, with marked decrease in the acetyl moiety. These results suggest that ADG is carrier of the acetyl group and a link in the formation of n-TG. Analysis of fatty acids in the lipids showed that the marker was also incorporated into the di-unsaturated acid fraction, which consisted almost entirely of linoleic acid suggesting the de novo synthesis of this fatty acid by the insect. In the experiment using ovipositing insects, the marker was found to be incorporated into the lipids in both the eggs and egg sacs, and also into the mother bodies indicating that the insects continue feeding even during the period of oviposition. (author)

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

    Directory of Open Access Journals (Sweden)

    Yang Z

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-04-12

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

  7. Treinamento neuromotor no padrão de marcha e na mobilidade de tornozelos em idosos

    Directory of Open Access Journals (Sweden)

    Bruna Caroline de Lima

    2015-12-01

    Full Text Available Objetivo: Analisar o efeito do treinamento neuromotor no padrão de marcha e a mobilidade de tornozelos em idosos. Métodos: Ensaio controlado não aleatorizado, de corte transversal, realizado em Rio Negrinho, Santa Catarina, no período de maio a setembro de 2015, com amostra de 26 idosas divididas em grupo controle (GC=15 e grupo treinamento neuromotor (GTN=11. A avaliação do padrão de marcha ocorreu através do Protocolo de Cerny e a mobilidade de tornozelos, através da goniometria. O GC realizou atividade física regular composta por aquecimento, exercícios de alongamento e fortalecimento muscular de grandes grupos musculares de membros e desaquecimento. O GTN recebeu treinamento neuromotor em forma de circuito composto por 10 estações, com aquecimento, treinamento neuromotor, desaquecimento e repetição do circuito em 3 vezes, com permanência de 1 minuto em cada estação e 30 segundos de intervalo entre elas, com progressão de dificuldade dos exercícios após a sexta semana. Ambos os grupos realizaram a atividade por 12 semanas (2 vezes semanais, com duração de 45 minutos. Análise ocorreu pelo teste t, adotando um nível de significância de p<0,05. Resultados: Houve melhora significativa em dorsiflexão de ambos os tornozelos (direito p=0,00 e esquerdo=0,02 e em ambos os grupos; já no padrão de marcha, não houve melhora significativa após treinamento neuromotor (velocidade p=0,55; tempo de deambulação p=0,6. Conclusão: O treinamento neuromotor beneficiou a manutenção do padrão de marcha (velocidade e tempo de deambulação e a mobilidade articular de tornozelos em idosas avaliadas.

  8. [Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region].

    Science.gov (United States)

    Maia, Marcelle Marie Martins; Lage, Eura Martins; Moreira, Bárbara Cecília Borges; Deus, Elayne Alayne Braga de; Faria, Joanna Gonçalves; Pinto, Jorge Andrade; Melo, Victor Hugo

    2015-09-01

    To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors. A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs. Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis. The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission.

  9. Experimental and numerical characterization of anisotropic damage evolution of forged Al6061-T6 alloy

    International Nuclear Information System (INIS)

    Shen, Y.; Garnier, J.; Allais, L.; Crepin, J.; Ancelet, O.; Hiver, J.M.

    2011-01-01

    Aluminum alloy 6061-T6 (Al-Mg-Si) has been selected as the material of the vessel for the construction of Jules-Horowitz material testing reactor. Fracture mechanism of this alloy has been investigated using mechanical testing of smooth and notched tensile specimens loaded in different directions. A strong anisotropic fracture behavior has been observed. Microstructural studies using tomography and image analysis have shown a presence of anisotropic distributed coarse precipitates which is the key microstructural feature affecting the damage evolution. These observations were complemented by investigations on fractured tensile samples. A damage scenario of anisotropic growth and coalescence of voids is proposed to explain the fracture behavior associated with the distribution of precipitates. A GTN (Gurson-Tvergaard-Needleman) damage model is used to simulate this scenario and to predict damage evolution. (authors)

  10. Properties and thermal decomposition of the double salts of uranyl nitrate-ammonium nitrate

    International Nuclear Information System (INIS)

    Notz, K.J.; Haas, R.A.

    1989-01-01

    The formation of ammonium nitrate-uranyl nitrate double salts has important effects on the thermal denitration process for the preparation of UO 3 and on the physical properties of the resulting product. Analyses were performed, and properties and decomposition behavior were determined for three double salts: NH 4 UO 2 (NO 3 ) 3 , (NH 4 ) 2 UO 2 (NO 3 ) 4 , and (NH 4 ) 2 UO 2 (NO 3 ) 4 ·2H 2 O. The tinitrate salt decomposes without melting at 270-300 C to give a γ-UO 3 powder of ∼3-μm average size, with good ceramic properties for fabrication into UO 2 nuclear fuel pellets. The tetranitrate dihydrate melts at 48 C; it also dehydrates to the anhydrous salt. The anhydrous tetranitrate decomposes exothermically, without melting, at 170-270 C by losing one mole of ammonium nitrate to form the trinitrate salt

  11. Management of cardiac arrest caused by coronary artery spasm: epinephrine/adrenaline versus nitrates.

    Science.gov (United States)

    Kiss, Gabor; Corre, Olivier; Gueret, Gildas; Nguyen Ba, Vinh; Gilard, Martine; Boschat, Jaques; Arvieux, Charles Chistian

    2009-01-01

    Cardiopulmonary resuscitation guidelines imply the use of epinephrine/adrenaline during cardiopulmonary arrest. However, in cardiac arrest situations resulting from coronary artery spasm (CAS), the use of epinephrine/adrenaline could be deleterious. A 49-year-old patient underwent an emergency coronarography with an attempt to stent the coronary arteries. Radiologic imaging revealed a positive methylergonovine maleate (Methergine, Novartis Pharmaceuticals, East Hanover, NJ) test, with subocclusive CAS in several coronary vessels leading to electromechanical dissociation. Cardiopulmonary resuscitation was performed, and intracoronary boluses of isosorbide dinitrate were given to treat CAS. Epinephrine/adrenaline was not administered during resuscitation. Spontaneous circulation was obtained after cardioversion for ventricular fibrillation, and the patient progressively regained consciousness. Resuscitation guidelines do not specify the use of trinitrate derivatives in cardiac arrest situations caused by CAS. The pros and cons of the use of nitrates and epinephrine/adrenaline during cardiac arrest caused by CAS are analyzed in this case report.

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

    Directory of Open Access Journals (Sweden)

    Kazunori Iwanaga

    2015-06-01

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

  13. Laboratory tests of headache disorders - Dawn of a new era?

    DEFF Research Database (Denmark)

    Schytz, Henrik Winther; Olesen, Jes

    2016-01-01

    secondary headaches. Background In this narrative review we present and discuss published tests that might be useful in phenotyping and/or diagnosis of long-lasting headache disorders such as migraine, tension-type headache, trigeminal autonomic cephalalgias, trigeminal neuralgia and persisting secondary...... headaches. Aim The palpometer test, quantitative sensory testing, nociceptive blink reflex and autonomic tests may be valuable to phenotype and/or diagnose subforms of migraine, tension-type headache, cluster headache, trigeminal neuralgia and medication-overuse headache. Provocation tests with glyceryl...... if well-reputed tertiary headache centers commence developing and implementing laboratory tests in order to improve the classification and treatment of headache patients....

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

    Energy Technology Data Exchange (ETDEWEB)

    Bronkhorst, Curt A [Los Alamos National Laboratory; Dennis - Koller, Darcie [Los Alamos National Laboratory; Cerreta, Ellen K [Los Alamos National Laboratory; Gray Ill, George T [Los Alamos National Laboratory; Bourne, Neil [AWE-ALDERMASTON

    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.

  15. Nitroglycerin provocation in normal subjects is not a useful human migraine model?

    DEFF Research Database (Denmark)

    Tvedskov, J F; Iversen, Helle Klingenberg; Olesen, J

    2010-01-01

    Provoking delayed migraine with nitroglycerin in migraine sufferers is a cumbersome model. Patients are difficult to recruit, migraine comes on late and variably and only 50-80% of patients develop an attack. A model using normal volunteers would be much more useful, but it should be validated...... aspirin 1000 mg, zolmitriptan 5 mg or placebo to normal healthy volunteers. The design was double-blind, placebo-controlled three-way crossover. Our hypothesis was that these drugs would be effective in the treatment of the mild constant headache induced by long-lasting GTN infusion. The headaches did...... experiment suggests that headache caused by direct nitric oxide (NO) action in the continued presence of NO is very resistance to analgesics and to specific acute migraine treatments. This suggests that NO works very deep in the cascade of events associated with vascular headache, whereas tested drugs work...

  16. Explosive double salts and preparation

    Science.gov (United States)

    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.

  17. Apparent and partial molal heat capacities of aqueous rare earth nitrate solutions at 250C

    International Nuclear Information System (INIS)

    Spedding, F.H.; Baker, J.L.; Walters, J.P.

    1979-01-01

    Specific heats of aqueous solutions of the trinitrates of La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu were measured from 0.1 m to saturation at 25 0 C. Apparent molal heat capacities, phi/sub cp/, were calculated for these solutions, and empirical polynomial equations were obtained which expressed phi/sub cp/ as a function of m/sup 1/2/ for each salt. The partial molal heat capacities of the solvent, anti C 1 /sub p/, and solute, anti C 2 /sub p/, were calculated from these equations. Unlike chloride and perchlorate data reported earlier, values of anti C 1 /sub p/ for nitrate solutions across the rare earth series did not show a two series effect. Instead, anti C 1 /sub p/ values at lower concentrations (0.5 and 1.0 m) appear correlated with reported first formation constants for rare earth-nitrate complexes. 31 references, 9 figures, 2 tables

  18. Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler.

    Science.gov (United States)

    Singh, Deepak J; Jain, Rajesh R; Soni, P S; Abdul, Samad; Darshana, Hegde; Gaikwad, Rajiv V; Menon, Mala D

    2015-08-01

    Dry powder inhalers (DPI) are generally formulated by mixing micronized drug particles with coarse lactose carrier particles to assist powder handling during the manufacturing and powder aerosol delivery during patient use. In the present study, surface modified lactose (SML) particles were produced using force control agents, and their in vitro performance on dry powder inhaler (DPI) formulation of Fluticasone propionate was studied. With a view to reduce surface passivation of high surface free energy sites on the most commonly used DPI carrier, α- lactose monohydrate, effects of various force control agents such as Pluronic F-68, Cremophor RH 40, glyceryl monostearate, polyethylene glycol 6000, magnesium stearate, and soya lecithin were studied. DPI formulations prepared with SML showed improved flow properties, and atomic force microscopy (AFM) studies revealed decrease in surface roughness. The DSC and X-ray diffraction patterns of SML showed no change in the crystal structure and thermal behavior under the experimental conditions. The fine particle fraction (FPF) values of lactose modified with Pluronic F-68, Cremophor RH 40, glyceryl monostearate were improved, with increase in concentration up to 0.5%. Soya lecithin and PEG 6000 modified lactose showed decrease in FPF value with increase in concentration. Increase in FPF value was observed with increasing concentration of magnesium stearate. Two different DPI devices, Rotahaler(®) and Diskhaler(®), were compared to evaluate the performance of SML formulations. FPF value of all SML formulations were higher using both devices as compared to the same formulations prepared using untreated lactose. One month stability of SML formulations at 40°C/75% RH, in permeable polystyrene tubes did not reveal any significant changes in FPF values. SML particles can help in reducing product development hindrances and improve inhalational properties of DPI.

  19. Using Internet-Based Robotic Telescopes to Engage Non-Science Majors in Astronomical Observation

    Science.gov (United States)

    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

  20. A new strategy for imaging biomolecular events through interactions between liquid crystals and oil-in-water emulsions.

    Science.gov (United States)

    Hu, Qiong-Zheng; Jang, Chang-Hyun

    2012-11-21

    In this study, we demonstrate a new strategy to image biomolecular events through interactions between liquid crystals (LCs) and oil-in-water emulsions. The optical response had a dark appearance when a nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), is in contact with emulsion droplets of glyceryl trioleate (GT). In contrast, the optical response had a bright appearance when 5CB is in contact with GT emulsions decorated with surfactants such as sodium oleate. Since lipase can hydrolyze GT and produce oleic acid, the optical response also displays a bright appearance after 5CB has been in contact with a mixture of lipase and GT emulsions. These results indicate the feasibility of monitoring biomolecular events through interactions between LCs and oil-in-water emulsions.

  1. Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation

    DEFF Research Database (Denmark)

    Andersen, A.D.H.; Lange, Marianne; Lillevang, S.T.

    2003-01-01

    The human chromosome region 2q33 including the three costimulatory molecules CD28, CTLA-4 and ICOS, has been subject to much attention due to its linkage to a number of autoimmune diseases. The search for the causal relationship of this linkage has revealed several polymorphisms, but no variations...... in the amino acid sequences except for one polymorphism in, the leader sequence of CTLA-4. In the present study, we examined the ICOS gene of an unrelated group of healthy donors from the Danish population. We were able to report 16 intronic SNP, one intronic G-insert and two repeat regions in intron 4......, consistent with the [T](n) and the [GT](n) regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of similar to3500 by of the upstream region of ICOS revealed an additional eight SNP of which two...

  2. Applications of meshless methods for damage computations with finite strains

    International Nuclear Information System (INIS)

    Pan Xiaofei; Yuan Huang

    2009-01-01

    Material defects such as cavities have great effects on the damage process in ductile materials. Computations based on finite element methods (FEMs) often suffer from instability due to material failure as well as large distortions. To improve computational efficiency and robustness the element-free Galerkin (EFG) method is applied in the micro-mechanical constitute damage model proposed by Gurson and modified by Tvergaard and Needleman (the GTN damage model). The EFG algorithm is implemented in the general purpose finite element code ABAQUS via the user interface UEL. With the help of the EFG method, damage processes in uniaxial tension specimens and notched specimens are analyzed and verified with experimental data. Computational results reveal that the damage which takes place in the interior of specimens will extend to the exterior and cause fracture of specimens; the damage is a fast procedure relative to the whole tensing process. The EFG method provides more stable and robust numerical solution in comparing with the FEM analysis

  3. Nelikvedu alt ei vea / Jussa Nieminen

    Index Scriptorium Estoniae

    Nieminen, Jussa

    2016-01-01

    Võrdlustestis talveauto 2016: Audi A4 Lim. 2,0 TDI Quattro S tronic, BMW X1 xDrive20d A, Fiat 500X 2,0 140 MJet AWD AT Cross, Ford S-Max 2,0 TDCi 180 hj PowerShift Titanium AWD, Hyundai Tucson 1,6 T-GDI 7DCT Style, Kia Sportage 1,6T GT-Line 7DCT, Land Rover Discovery Sport 2,0 TD4 180 HSE A, Mazda CX-3 2,0 Skyactiv-G AWD Premium Plus AT, Mercedes-Benz GLC 250 d 4Matic, Renault Kadjar 1,6 dCi 4×4 Bose, Škoda Superb Combi 2,0 TDI SCR DSG 4×4 L&K, Ssangyong Korando D20 AWD 6AT, Subaru Levorg 1,6i GT-N CVT, Suzuki Vitara 1,4 Boosterjet 4WD S 6MT, Volvo V60 Cross Country D4 AWD Inscription A Võrdluseks esiveoline: Toyota Auris Touring Sports1,8 Hybrid e-CVT Active

  4. Changes in subcellular distribution of n-octanoyl or n-decanoyl ghrelin in ghrelin-producing cells

    Directory of Open Access Journals (Sweden)

    Yoshihiro eNishi

    2013-07-01

    Full Text Available Background: The enzyme ghrelin O-acyltransferase (GOAT catalyzes the acylation of ghrelin. The molecular form of GOAT, together with its reaction in vitro, has been reported previously. However, the sub-cellular processes governing the acylation of ghrelin remain to be elucidated.Methods: Double immunoelectron microscopy was used to examine changes in the relative proportions of secretory granules containing n-octanoyl ghrelin (C8-ghrelin or n-decanoyl ghrelin (C10-ghrelin in ghrelin-producing cells of mouse stomachs. The dynamics of C8-type (possessing C8-ghrelin exclusively, C10-type (possessing C10-ghrelin only and mixed-type secretory granules (possessing both C8- and C10-ghrelin were investigated after fasting for 48h or after two weeks’ feeding with chow containing glyceryl-tri-octanoate (C8-MCT or glyceryl-tri-decanoate (C10-MCT. The dynamics of C8- or C10-ghrelin immunoreactivity (ir-C8- or ir-C10-ghrelin within the mixed-type granules were also investigated.Results: Immunoelectron microscopic analysis revealed the co-existence of C8- and C10-ghrelin within the same secretory granules (mixed-type in ghrelin-producing cells. Compared to control mice fed standard chow, the ratio of C10-type secretory granules increased significantly after ingestion of C10-MCT, whereas that of C8-type granules declined significantly under the same treatment. After ingestion of C8-MCT, the proportion of C8-type secretory granules increased significantly. Within the mixed-type granules the ratio of ir-C10-ghrelin increased significantly and that of ir-C8-ghrelin decreased significantly upon fasting. Conclusions: These findings confirmed that C10-ghrelin, another acyl-form of active ghrelin, is stored within the same secretory granules as C8-ghrelin, and suggested that the types of medium-chain acyl-molecules surrounding and available to the ghrelin-GOAT system may affect the physiological processes of ghrelin acylation.

  5. Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

    Science.gov (United States)

    Nishi, Yoshihiro; Mifune, Hiroharu; Yabuki, Akira; Tajiri, Yuji; Hirata, Rumiko; Tanaka, Eiichiro; Hosoda, Hiroshi; Kangawa, Kenji; Kojima, Masayasu

    2013-01-01

    Background: The enzyme ghrelin O-acyltransferase (GOAT) catalyzes the acylation of ghrelin. The molecular form of GOAT, together with its reaction in vitro, has been reported previously. However, the subcellular processes governing the acylation of ghrelin remain to be elucidated. Methods: Double immunoelectron microscopy was used to examine changes in the relative proportions of secretory granules containing n-octanoyl ghrelin (C8-ghrelin) or n-decanoyl ghrelin (C10-ghrelin) in ghrelin-producing cells of mouse stomachs. The dynamics of C8-type (possessing C8-ghrelin exclusively), C10-type (possessing C10-ghrelin only), and mixed-type secretory granules (possessing both C8- and C10-ghrelin) were investigated after fasting for 48 h or after 2 weeks feeding with chow containing glyceryl-tri-octanoate (C8-MCT) or glyceryl-tri-decanoate (C10-MCT). The dynamics of C8- or C10-ghrelin-immunoreactivity (ir-C8- or ir-C10-ghrelin) within the mixed-type granules were also investigated. Results: Immunoelectron microscopic analysis revealed the co-existence of C8- and C10-ghrelin within the same secretory granules (mixed-type) in ghrelin-producing cells. Compared to control mice fed standard chow, the ratio of C10-type secretory granules increased significantly after ingestion of C10-MCT, whereas that of C8-type granules declined significantly under the same treatment. After ingestion of C8-MCT, the proportion of C8-type secretory granules increased significantly. Within the mixed-type granules the ratio of ir-C10-ghrelin increased significantly and that of ir-C8-ghrelin decreased significantly upon fasting. Conclusion: These findings confirmed that C10-ghrelin, another acyl-form of active ghrelin, is stored within the same secretory granules as C8-ghrelin, and suggested that the types of medium-chain acyl-molecules surrounding and available to the ghrelin-GOAT system may affect the physiological processes of ghrelin acylation. PMID:23847595

  6. Kinetic, Thermodynamic and Process Modeling of Synthesis of UV Curable Glyceryl and Neopentyl Glycol Acrylates

    OpenAIRE

    R. D. Kulkarni; Mayur Chaudhari; S. Mishra

    2008-01-01

    Curing of paints by exposure to UV radiations is emerging as one of the best film forming technique as an alternative to traditional solvent borne oxidative and thermal curing coatings. The composition and chemistry of UV curable coatings and role of multifunctional and monofunctional monomers, oligomers, and photoinitiators have been discussed. The limitations imposed by thermodynamic equilibrium and tendency for acrylic double bond polymerizations during synthesis of mu...

  7. Autoradiographic study on percutaneous absorption of several oils useful for cosmetics

    International Nuclear Information System (INIS)

    Suzuki, M.; Asaba, K.; Komatsu, H.; Mochizuka, M.

    1978-01-01

    Percutaneous absorption of five 14 C-labelled oils, n-octadecane, decanoxy decane, 2-hexyldecanoxy octane, isopropyl myristate and glyceryl tri-(oleate), commonly used is cosmetics were studied from the point of view of their safety. In whole body autoradiography of hairless mice, there was no visible penetration into the skin and organs, whereas microautoradiography of guinea pigs showed local penetration. Isopropyl myristate penetrated to the greatest extent, whereas 2-hexyldecanoxy octane was hardly absorbed. Percutaneous absorption of these two oils, therefore, was examined in Angora rabbits by microautoradiography simultaneously with skin irritation potential by a histological method, from the following aspects, (1) patterns of penetration and irritation in relation to application time and (2) fate within the skin and pattern of irritation after application. In addition, intradermal metabolic fate was studied in vivo. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Tensile and fracture behavior of AA6061-T6 aluminum alloys: micro-mechanical approach

    International Nuclear Information System (INIS)

    Shen, Y.

    2012-01-01

    The AA6061-T6 aluminum alloy was chosen as the material for the core vessel of the future Jules Horowitz testing reactor (JHR). The objective of this thesis is to understand and model the tensile and fracture behavior of the material, as well as the origin of damage anisotropy. A micro-mechanical approach was used to link the microstructure and mechanical behavior. The microstructure of the alloy was characterized on the surface via Scanning Electron Microscopy and in the 3D volume via synchrotron X-ray tomography and laminography. The damage mechanism was identified by in-situ SEM tensile testing, ex-situ X-ray tomography and in-situ laminography on different levels of triaxiality. The observations have shown that damage nucleated at lower strains on Mg 2 Si coarse precipitates than on iron rich intermetallics. The identified scenario and the in-situ measurements were then used to develop a coupled GTN damage model incorporating nucleation, growth and coalescence of cavities formed by coarse precipitates. The relationship between the damage and the microstructure anisotropies was explained and simulated. (author)

  10. Towards Industrial Application of Damage Models for Sheet Metal Forming

    Science.gov (United States)

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

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Jisun, E-mail: nskim@sogang.ac.kr; Lee, Hyungyil, E-mail: nskim@sogang.ac.kr; Kim, Dongchul, E-mail: nskim@sogang.ac.kr; Kim, Naksoo, E-mail: nskim@sogang.ac.kr [Sogang University, Department of Mechanical Engineering, Seoul, 121-742 (Korea, Republic of)

    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.

  12. Use of the glyceryl guaiacolate alone and associated with levomepromazine and benzodiazepines in gelding of horses

    Directory of Open Access Journals (Sweden)

    Flavio Massone

    1990-12-01

    caracterizar-se por valores maiores de freqüência respiratória que os demais grupos. As três técnicas anestésicas mostraram-se satisfatórias, pela estabilidade de parâmetros fisiológicos e indução e recuperação suaves, sendo que a associação da levomepromazina com o flunitrazepan ou midazolam proporcionou prostração mais eficaz, bem como maior miorrelaxamento, sedação e hipoalgesia.

  13. Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method

    Directory of Open Access Journals (Sweden)

    Zaida Urbán-Morlán

    2010-08-01

    Full Text Available Zaida Urbán-Morlán1, Adriana Ganem-Rondero1, Luz María Melgoza-Contreras2, José Juan Escobar-Chávez1,2, María Guadalupe Nava-Arzaluz1, David Quintanar-Guerrero11División de Estudios de Posgrado (Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Estado de México, México; 2Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso, Colonia Villa Quietud, MéxicoAbstract: Solid lipid nanoparticles (SLNs have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol® ATO 888 and lauroyl macrogolglycerides (Gelucire® 44/14 were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire®, while it was difficult to obtain stable systems with Compritol®. Systems with Gelucire® were characterized by particle size, Z-potential, differential scanning calorimetry (DSC, scanning electron microscopy (SEM, entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg in Gelucire® SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid’s partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    The objective was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned and regional renal blood flow determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed...... of one voxel were eliminated stepwise from the external surface of the VOI ('voxel peeling'), and the blood flow subsequently determined in each new, reduced VOI. Blood flow in the shrinking volumes of interest (VOIs) decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood...... flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ±0.17 ml·(g·min)(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ±0.18 ml·(g·min)(-1) (p...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were......-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which...... the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans....

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

    Directory of Open Access Journals (Sweden)

    Ritmaleni Ritmaleni

    2013-11-01

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

  17. Physico-chemical characterisation, cytotoxic activity, and biocompatibility studies of tamoxifen-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification method.

    Science.gov (United States)

    Lakkadwala, Sushant; Nguyen, Sanko; Lawrence, Joseph; Nauli, Surya M; Nesamony, Jerry

    2014-01-01

    Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. To prepare and characterise tamoxifen (TAM)-loaded SLNs. Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system.

  18. Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Rades, Thomas; Boyd, Ben

    2017-01-01

    The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric...... microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor...... the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after...

  19. A Study On Critical Thinning In Thin-walled Tube Bending Of Al-Alloy 5052O Via Coupled Ductile Fracture Criteria

    International Nuclear Information System (INIS)

    Li Heng; Yang He; Zhan Mei

    2010-01-01

    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.

  20. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.

    Science.gov (United States)

    Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Mahmood, Asif; Maheen, Safirah; Afzal, Khurram; Iqbal, Nabila; Andleeb, Mehwish; Abbas, Nazar

    2017-12-20

    For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  1. Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain.

    Science.gov (United States)

    Morgan, Amanda J; Kingsley, Philip J; Mitchener, Michelle M; Altemus, Megan; Patrick, Toni A; Gaulden, Andrew D; Marnett, Lawrence J; Patel, Sachin

    2018-05-09

    Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs.

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

    Science.gov (United States)

    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.

  3. Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

    Science.gov (United States)

    Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

    2018-01-01

    Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-04-15

    Since the polar paradox theory rationalised the fact that polar antioxidants are more effective in nonpolar media, extractions of phenolic compounds in vegetable oils were inspired and achieved in this study for obtaining oils enriched in phenolic compounds. Moreover, the influence of surfactants on the extractability of phenolic compounds was experimentally studied first, followed by the small angle X-ray scattering analysis for the oil structural observation before and after extraction so as to better understand the dissolving mechanism underpinning the extraction. The results showed a significant difference on the extraction yield of phenolic compounds among oils, which was mainly dependent on their composition instead of the unsaturation of fatty acids. Appropriate surfactant additions could significantly improve extraction yield for refined sunflower oils, which 1% w/w addition of glyceryl oleate was determined as the optimal. Besides, 5% w/w addition of lecithin performed the best in oil enrichments compared with mono- and di-glycerides. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Mahdi ES

    2011-10-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Endothelial function in highly endurance-trained and sedentary, healthy young women.

    Science.gov (United States)

    Moe, Ingvild T; Hoven, Heidi; Hetland, Eva V; Rognmo, Oivind; Slørdahl, Stig A

    2005-05-01

    Endothelial function is reduced by age, chronic heart failure, coronary artery disease, hypertension or type 2 diabetes, and it is shown that aerobic exercise may reverse this trend. The effect of a high aerobic training status on endothelial function in young, healthy subjects is however less clear. The present study was designed to determine whether endothelial function is improved in highly endurance-trained young women compared to sedentary, healthy controls. Brachial artery diameter was measured in 16 endurance-trained (age: 23.7 +/- 2.5 years, maximal oxygen uptake (VO2max): 60.6 +/- 4.5 ml/kg per min) and 14 sedentary females (age: 23.7 +/- 2.1 years, VO2max: 40.5 +/- 5.6 ml/kg per min) at rest, during flow-mediated dilation (FMD) and after sublingual glycerol trinitrate administration, using high-resolution ultrasound. FMD did not differ between the endurance-trained and the sedentary females (14.8% vs 16.4%, p = NS), despite a substantial difference in VO2max of 50% (p endurance-trained group possessed however, a 9% larger resting brachial artery diameter when adjusted for body surface area. The results of the present study suggest that endothelial function is well preserved in young, healthy women, and that a high aerobic training status due to long term aerobic training does not improve the dilating capacity any further.

  9. Molecular weights and molecular weight distributions of irradiated cellulose fibers by gel permeation chromatography

    International Nuclear Information System (INIS)

    Kusama, Y.; Kageyama, E.; Shimada, M.; Nakamura, Y.

    1976-01-01

    Radiation degradation of cellulose fibers was investigated by gel permeation chromatography (GPC). Scoured cotton of Mexican variety (cellulose I), Polynosic rayon (cellulose II), and their microcrystalline celluloses obtained by hydrolysis of the original fibers were irradiated by Co-60 γ-rays under vacuum or humid conditions. The irradiated samples were then nitrated under nondegradative conditions. The molecular weights and molecular weight distributions were measured by GPC using tetrahydrofuran as solvent. The relationship between molecular weight and elution count was obtained with cellulose trinitrate standards fractionated by preparative GPC. The degree of polymerization of the fibers decreased with increasing irradiation dose, but their microcrystalline celluloses were only slightly degraded by irradiation, especially in microcrystalline cellulose from cellulose I. Degradation of the fibers irradiated under humid conditions was less than that irradiated under vacuum. It was found that the G-values for main-chain scission for the irradiated cellulose I, cellulose II, microcrystalline cellulose I, and microcrystalline cellulose II were 2.8, 2.9, less than 1, and 2.9, respectively, but the G-value for main-chain scission for the irradiated cellulose II was increased to 11.2 at irradiation doses above 3 Mrad. Consequently, it is inferred that cellulose molecules in the amorphous regions are degraded more readily, and the well-aligned molecules in crystalline regions are not as easily degraded by irradiation

  10. Assessment of Constraint Effects based on Local Approach

    International Nuclear Information System (INIS)

    Lee, Tae Rin; Chang, Yoon Suk; Choi, Jae Boong; Seok, Chang Sung; Kim, Young Jin

    2005-01-01

    Traditional fracture mechanics has been used to ensure a structural integrity, in which the geometry independence is assumed in crack tip deformation and fracture toughness. However, the assumption is applicable only within limited conditions. To address fracture covering a broad range of loading and crack geometries, two-parameter global approach and local approach have been proposed. The two-parameter global approach can quantify the load and crack geometry effects by adopting T-stress or Q-parameter but time-consuming and expensive since lots of experiments and finite element (FE) analyses are necessary. On the other hand, the local approach evaluates the load and crack geometry effects based on damage model. Once material specific fitting constants are determined from a few experiments and FE analyses, the fracture resistance characteristics can be obtained by numerical simulation. The purpose of this paper is to investigate constraint effects for compact tension (CT) specimens with different in-plane or out-of-plane size using local approach. Both modified GTN model and Rousselier model are adopted to examine the ductile fracture behavior of SA515 Gr.60 carbon steel at high temperature. The fracture resistance (J-R) curves are estimated through numerical analysis, compared with corresponding experimental results and, then, crack length, thickness and side-groove effects are evaluated

  11. How do glacier inventory data aid global glacier assessments and projections?

    Science.gov (United States)

    Hock, R.

    2017-12-01

    Large-scale glacier modeling relies heavily on datasets that are collected by many individuals across the globe, but managed and maintained in a coordinated fashion by international data centers. The Global Terrestrial Network for Glaciers (GTN-G) provides the framework for coordinating and making available a suite of data sets such as the Randolph Glacier Inventory (RGI), the Glacier Thickness Dataset or the World Glacier Inventory (WGI). These datasets have greatly increased our ability to assess global-scale glacier mass changes. These data have also been vital for projecting the glacier mass changes of all mountain glaciers in the world outside the Greenland and Antarctic ice sheet, a total >200,000 glaciers covering an area of more than 700,000 km2. Using forcing from 8 to 15 GCMs and 4 different emission scenarios, global-scale glacier evolution models project multi-model mean net mass losses of all glaciers between 7 cm and 24 cm sea-level equivalent by the end of the 21st century. Projected mass losses vary greatly depending on the choice of the forcing climate and emission scenario. Insufficiently constrained model parameters likely are an important reason for large differences found among these studies even when forced by the same emission scenario, especially on regional scales.

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

    Directory of Open Access Journals (Sweden)

    Thomas Lawyer

    2012-01-01

    Full Text Available 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.

  13. Prognostic Factors Influencing the Patency of Hemodialysis Vascular Access: Literature Review and Novel Therapeutic Modality by Far Infrared Therapy

    Directory of Open Access Journals (Sweden)

    Chih-Ching Lin

    2009-03-01

    Full Text Available In Taiwan, more than 85% of patients with end-stage renal disease undergo maintenance hemodialysis (HD. The native arteriovenous fistula (AVF accounts for a prevalence of more than 80% of the vascular access in our patients. Some mechanical factors may affect the patency of hemodialysis vascular access, such as surgical skill, puncture technique and shear stress on the vascular endothelium. Several medical factors have also been identified to be associated with vascular access prognosis in HD patients, including stasis, hypercoagulability, endothelial cell injury, medications, red cell mass and genotype polymorphisms of transforming growth factor-β1 and methylene tetrahydrofolate reductase. According to our previous study, AVF failure was associated with a longer dinucleotide (GTn repeat (n ≥ 30 in the promoter of the heme oxygenase-1 (HO-1 gene. Our recent study also demonstrated that far-infrared therapy, a noninvasive and convenient therapeutic modality, can improve access flow, inflammatory status and survival of the AVF in HD patients through both its thermal and non-thermal (endothelial-improving, anti-inflammatory, antiproliferative, antioxidative effects by upregulating NF-E2-related factor-2-dependent HO-1 expression, leading to the inhibition of expression of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1.

  14. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

    Directory of Open Access Journals (Sweden)

    Hanif Muhammad

    2017-12-01

    Full Text Available For preparing nebivolol loaded solid lipid microparticles (SLMs by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1, entrapment efficiency (Y2 and drug release (Y3. SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV. The obtained outcomes for Y1 (29-86 %, Y2 (45-83 % and Y3 (49-86 % were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  15. Sesquiterpenes from the Saudi Red Sea: Litophyton arboreum with their cytotoxic and antimicrobial activities.

    Science.gov (United States)

    Abou El-Kassem, Lamia T; Hawas, Usama W; El-Desouky, Samy K; Al-Farawati, Radwan

    2018-01-26

    A new pseudoguaiane-type sesquiterpene named litopharbol (1) was isolated from the methanolic extract of the Red Sea soft coral Litophyton arboreum, along with known sesquiterpenoids alismol (2), alismorientol B (3), teuhetenone A (4), and calamusin I (5); steroid, 24-methyl-cholesta-5,24(28)-diene-3β-ol (6), alkyl glyceryl ether, chimyl alcohol (7); sphingolipid, erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8); and nitrogenous bases, thymine (9) and thymidine (10). The structures were determined on the basis of nuclear magnetic resonance (NMR) spectroscopic (1D and 2D NMR data including heteronuclear single quantum coherence spectroscopy, heteronuclear multiple-bond correlation spectroscopy, and nuclear Overhauser effect spectroscopy) and mass spectrometric analyses. Compounds 1-5 were explored for antimicrobial activity and cancer cell line sensitivity tests. Compound 1 exhibited antibacterial activity against Bacillus cereus with a minimum inhibition concentration of 1.8 μg/mL, whereas compound 3 showed significant potent cytotoxic effect against MCF-7 (breast cancer cells) with IC50 4.32 μM.

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

    Science.gov (United States)

    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.

  17. Speciation of arsenic in marine food (Anemonia sulcata) by liquid chromatography coupled to inductively coupled plasma mass spectrometry and organic mass spectrometry.

    Science.gov (United States)

    Contreras-Acuña, M; García-Barrera, T; García-Sevillano, M A; Gómez-Ariza, J L

    2013-03-22

    Arsenic species have been investigated in Anemonia sulcata, which is frequently consumed food staple in Spain battered in wheat flour and fried with olive oil. Speciation in tissue extracts was carried out by anion/cation exchange chromatography with inductively coupled plasma mass spectrometry (HPLC-(AEC/CEC)-ICP-MS). Three methods for the extraction of arsenic species were investigated (ultrasonic bath, ultrasonic probe and focused microwave) and the optimal one was applied. Arsenic speciation was carried out in raw and cooked anemone and the dominant species are dimethylarsinic acid (DMA(V)) followed by arsenobetaine (AB), As(V), monomethylarsonic acid (MA(V)), tetramethylarsonium ion (TETRA) and trimethylarsine oxide (TMAO). In addition, arsenocholine (AsC), glyceryl phosphorylarsenocholine (GPAsC) and dimethylarsinothioic acid (DMAS) were identified by liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-MS). These results are interesting since GPAsC has been previously reported in marine organisms after experimental exposure to AsC, but not in natural samples. In addition, this paper reports for the first time the identification of DMAS in marine food. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Conférence Chevreul

    Directory of Open Access Journals (Sweden)

    Mouloungui Zéphirin

    2004-11-01

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

  19. The In Vitro-In Vivo Safety Confirmation of PEG-40 Hydrogenated Castor Oil as a Surfactant for Oral Nanoemulsion Formulation.

    Science.gov (United States)

    Rachmawati, Heni; Novel, Miranti Anggraeni; Ayu, Sri; Berlian, Guntur; Tandrasasmita, Olivia Mayasari; Tjandrawinata, Raymond Rubianto; Anggadiredja, Kusnandar

    2017-03-31

    Evaluation on the safety use of high concentration of polyoxyl 40 (PEG-40) hydrogenated castor oil as a surfactant for oral nanoemulsion was performed in Webster mice. As previously reported, nearly 20% of PEG-40 hydrogenated castor oil was used to emulsify the glyceryl monooleate (GMO) as an oil to the aqueous phase. Thermodynamically stable and spontaneous nanoemulsion was formed by the presence of co-surfactant polyethylene glycol 400 (PEG-400). Standard parameters were analyzed for nanoemulsion including particle size and particle size distribution, the surface charge of nanoemulsion, and morphology. To ensure the safety of this nanoemulsion, several cell lines were used for cytotoxicity study. In addition, 5000 mg/kg body weight (BW) of the blank nanoemulsion was given orally to Webster mice once a day for 14 days. Several parameters such as gross anatomy, body weight, and main organs histopathology were observed. In particular, by considering the in vivo data, it is suggested that nanoemulsion composed with a high amount of PEG-40 hydrogenated castor oil is acceptable for oral delivery of active compounds.

  20. Enhancement of dimple formability in sheet metals by 2-step forming

    International Nuclear Information System (INIS)

    Kim, Minsoo; Bang, Sungsik; Lee, Hyungyil; Kim, Naksoo; Kim, Dongchoul

    2014-01-01

    Highlights: • Suggested 2-step model aims at a lower susceptibility to cracking. • Strain at weak point could be reduced by 16% compared to 1-step model. • A more uniform thickness distribution is achieved by the 2-step model. • The maximum stress in the FLSD and the GTN damage variable reduced at the weak point. • The 2-step model provides an enhanced formability compared to the 1-step model. - Abstract: In this study, a 2-step stamping model with an additional 1st stamping tool is proposed to reduce stamping flaws in the curved parts of dimples in nuclear fuel spacer grids. First, the strains in the curved part of the dimple are analyzed and compared with strain solutions for pure bending. A reference 2D FE (finite element) model of the 1-step stamping is established, and the corresponding maximum strain is obtained. FE solutions are obtained for various process variable values for the 1st stamping tool used in the 2-step stamping model. Based on these solutions and applying the RSM (response surface method), strains are expressed as a function of process variables. This function then serves to evaluate optimum process variable values. Finally, by transferring these optimum values to a 3D FE model, we confirm the enhanced formability of the proposed 2-step stamping model

  1. MOLA HIDATIFORME: UM RELATO DE CASO

    Directory of Open Access Journals (Sweden)

    Felipe José Amaral de Castro¹

    2016-06-01

    Full Text Available Objectives: We relate a case of gestational throphoblastic neoplasia (GTN of the complete hydatiform mole variant occurred in the city of Anápolis-GO and also revised the literature about the subject. Case report: In first gynecological consultaltion pacient shows high levels of beta-HCG, uterine height imcompatible with gestational age and inaudible fetal heart beat. The ultrasound confirms gestational trophoblastic neoplasia being done the first curettage as soon as possible. With a month being passed are realized two more curetagges and the patient is forwarded to the Santa Casa of Anápolis, where after further examination were found beta-HCG of 142000 mUI/ml and hemoglobin of 10,3 g/dl. Her fourth curettage is realized and she is indicated to follow therapy in the Cancer Hospital of Anápolis. However, before that, she returns to the Santa Casa with pelvic aching, living and bright red vaginal bleeding, with no odor associated, following, therefore, with new betaHCG dosage (52475,46 mUI/mL e with new curettage being done. Currently, patient continues in chemotherapy and has progressively decreasing beta-HCG levels. Final considerations:We emphasize with this story description the necessity of appreciation of pre-natal routines aiming the correct and premature diagnosis of the variety of NTG cases, as also the adequate following in the expectation of preventing relapses.

  2. Wax-incorporated emulsion gel beads of calcium pectinate for intragastric floating drug delivery.

    Science.gov (United States)

    Sriamornsak, Pornsak; Asavapichayont, Panida; Nunthanid, Jurairat; Luangtana-Anan, Manee; Limmatvapirat, Sontaya; Piriyaprasarth, Suchada

    2008-01-01

    The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

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

    Directory of Open Access Journals (Sweden)

    Harshal Ashok Pawar

    2014-01-01

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

  4. Triacrylate of glycerin synthesis and use in network polymer;Sintese do triacrilato de glicerina e seu uso como agente de ligacao cruzada

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Reinaldo Y.; Zawadzki, Sonia F.; Barbosa, Ronilson V., E-mail: yomorita1@hotmail.co [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Centro Politecnico

    2009-07-01

    The goal of this work was the synthesis and characterization of a new cross linker: the glyceryl triacrylate. The synthesis was done by an esterification reaction between glycerin and acrylic acid and the product, called GA, was characterized by infrared and nuclear magnetic resonance (NMR- 1a) spectroscopy. The behavior was analysed after a copolymerization with methyl methacrylate monomer (MMA). It was also prepared the PMMA and GA homopolymers. The addition of glycerin triacrylate up to 2 % in the MMA monomer changed the solubility of the copolymer. This one became insoluble in organic solvents in which the pure linear poly(methyl methacrylate) was soluble. Thermal analysis showed that the addition of 2% GA didn't change the Tg value of the PMMA pure, but the GA homopolymer showed a Tg value equal to 180 C, lower than expected. It seems that GA product is working as cross linker, but some insaturation links did not react. They remain as pendent groups, causing the Tg lowering. The results suggest that the new product can be used as cross linker for the application in acrylic polymers. (author)

  5. Transdermal delivery of paeonol using cubic gel and microemulsion gel

    Science.gov (United States)

    Luo, Maofu; Shen, Qi; Chen, Jinjin

    2011-01-01

    Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

  6. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

    Science.gov (United States)

    Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

    2018-06-01

    Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

  7. Effect of chloroquine on intestinal lipid metabolism

    International Nuclear Information System (INIS)

    Mansbach, C.M. II; Arnold, A.; Garrett, M.

    1987-01-01

    Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relative to the infused [ 3 H]TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated

  8. Triacrylate of glycerin synthesis and use in network polymer

    International Nuclear Information System (INIS)

    Morita, Reinaldo Y.; Zawadzki, Sonia F.; Barbosa, Ronilson V.

    2009-01-01

    The goal of this work was the synthesis and characterization of a new cross linker: the glyceryl triacrylate. The synthesis was done by an esterification reaction between glycerin and acrylic acid and the product, called GA, was characterized by infrared and nuclear magnetic resonance (NMR- 1a) spectroscopy. The behavior was analysed after a copolymerization with methyl methacrylate monomer (MMA). It was also prepared the PMMA and GA homopolymers. The addition of glycerin triacrylate up to 2 % in the MMA monomer changed the solubility of the copolymer. This one became insoluble in organic solvents in which the pure linear poly(methyl methacrylate) was soluble. Thermal analysis showed that the addition of 2% GA didn't change the Tg value of the PMMA pure, but the GA homopolymer showed a Tg value equal to 180 C, lower than expected. It seems that GA product is working as cross linker, but some insaturation links did not react. They remain as pendent groups, causing the Tg lowering. The results suggest that the new product can be used as cross linker for the application in acrylic polymers. (author)

  9. Internationally coordinated glacier monitoring: strategy and datasets

    Science.gov (United States)

    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

  10. A study of the compressibility and properties of tablets from co-processed dry binder composed of microcrystalline cellulose and glyceryl monostearate.

    OpenAIRE

    Muchová, Sandra

    2013-01-01

    The paper studies the co-processed dry binder LubriTose™ MCC from the viewpoint of energy evaluation of the compression process, strength and disintegration time of tablets. The results were compared with the identical evaluation of physical mixtures of microcrystalline cellulose with several types of lubricants. LubriTose™ MCC showed the lowest value of energy for friction, the highest value of energy accumulated by the tablet, and the highest plasticity of all tableting materials under stud...

  11. CCDC 782644: Experimental Crystal Structure Determination : tetrakis(mu~2~-4,5-imidazoledicarboxylato)-tetrakis(1,2-propanediamine)-tetra-indium tri-potassium trinitrate acetonitrile solvate hydrate

    KAUST Repository

    Wang, Shuang; Zhao, Tingting; Li, Guanghua; Wojtas, L.; Huo, Qisheng; Eddaoudi, Mohamed; Liu, Yunling

    2011-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  12. Formability prediction for AHSS materials using damage models

    Science.gov (United States)

    Amaral, R.; Santos, Abel D.; José, César de Sá; Miranda, Sara

    2017-05-01

    Advanced high strength steels (AHSS) are seeing an increased use, mostly due to lightweight design in automobile industry and strict regulations on safety and greenhouse gases emissions. However, the use of these materials, characterized by a high strength to weight ratio, stiffness and high work hardening at early stages of plastic deformation, have imposed many challenges in sheet metal industry, mainly their low formability and different behaviour, when compared to traditional steels, which may represent a defying task, both to obtain a successful component and also when using numerical simulation to predict material behaviour and its fracture limits. Although numerical prediction of critical strains in sheet metal forming processes is still very often based on the classic forming limit diagrams, alternative approaches can use damage models, which are based on stress states to predict failure during the forming process and they can be classified as empirical, physics based and phenomenological models. In the present paper a comparative analysis of different ductile damage models is carried out, in order numerically evaluate two isotropic coupled damage models proposed by Johnson-Cook and Gurson-Tvergaard-Needleman (GTN), each of them corresponding to the first two previous group classification. Finite element analysis is used considering these damage mechanics approaches and the obtained results are compared with experimental Nakajima tests, thus being possible to evaluate and validate the ability to predict damage and formability limits for previous defined approaches.

  13. An investigative study into psychological and fertility sequelae of gestational trophoblastic disease: the impact on patients' perceived fertility, anxiety and depression.

    Science.gov (United States)

    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

    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. 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 (statistic. Three-way ANOVAs were also carried out considering the same block factors. 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. 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.

  14. 99mTcN-gatifloxacin dithiocarbamate complex. A novel multi-drug-resistance Streptococcus pneumoniae (MRSP) infaction radiotracer

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Mohammad Rafiullah Khan

    2011-01-01

    Gatifloxacin (GTN) was derivatized to its dithiocarbamate derivative and its radiolabeling with technetium-99m ( 99m Tc) using the [ 99m Tc≡N] 2+ core was investigated. The appropriateness of the 99m TcN - gatifloxacin dithiocarbamate ( 99m TcN - GTND) complex as a potential multi-drug-resistance Streptococcus pneumoniae (MRSP) infection radiotracer was evaluated in terms of stability in saline, serum, in vitro binding with MRSP and biodistribution in artificially MRSP infected Male Wistar Rats (MWR). In saline the 99m TcN - GTND complex showed more than 90% labeling yield up to 4 h with a maximum yield of 98.25 ± 0.20%, after reconstitution. In serum the 99m TcN - GTND complex showed stability up to 16 h of incubation with the appearance of insignificant 15.95% undesirable side products. The 99m TcN - GTND complex demonstrated saturated in vitro binding with MRSP with a maximum value of 75.50 ± 1.00% (at 90 min). In MWR model of group A, almost six times higher uptake of the labeled GTND was monitored in the muscle of MWR infected with live MRSP as compared to the inflamed and normal muscles. Based on the higher labeling yield in saline, in vitro stability in serum, saturated in vitro binding with live MRSP and promising biodistribution in MWR model we recommend 99m TcN - gatifloxacin dithiocarbamate complex as a potential MRSP infection radiotracer. (author)

  15. Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Wei, Jiafu; Wu, Taixiang; Yang, Qing; Chen, Mao; Ni, Juan; Huang, Dejia

    2011-01-07

    To assess the effect (harms and benefits) of nitrates for stable angina. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Formability prediction for AHSS materials using damage models

    International Nuclear Information System (INIS)

    Amaral, R.; Miranda, Sara; Santos, Abel D.; José, César de Sá

    2017-01-01

    Advanced high strength steels (AHSS) are seeing an increased use, mostly due to lightweight design in automobile industry and strict regulations on safety and greenhouse gases emissions. However, the use of these materials, characterized by a high strength to weight ratio, stiffness and high work hardening at early stages of plastic deformation, have imposed many challenges in sheet metal industry, mainly their low formability and different behaviour, when compared to traditional steels, which may represent a defying task, both to obtain a successful component and also when using numerical simulation to predict material behaviour and its fracture limits. Although numerical prediction of critical strains in sheet metal forming processes is still very often based on the classic forming limit diagrams, alternative approaches can use damage models, which are based on stress states to predict failure during the forming process and they can be classified as empirical, physics based and phenomenological models. In the present paper a comparative analysis of different ductile damage models is carried out, in order numerically evaluate two isotropic coupled damage models proposed by Johnson-Cook and Gurson-Tvergaard-Needleman (GTN), each of them corresponding to the first two previous group classification. Finite element analysis is used considering these damage mechanics approaches and the obtained results are compared with experimental Nakajima tests, thus being possible to evaluate and validate the ability to predict damage and formability limits for previous defined approaches. (paper)

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

    KAUST Repository

    Urban, Jiří T.

    2011-09-26

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

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

    KAUST Repository

    Urban, Jiří T.; Švec, František; Frechet, Jean

    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 2h to carry out the immobilization of the enzyme. Best conditions for the transesterification of glyceryl tributyrate included a temperature of 37°C and a 10min residence time of the substrate in the bioreactor. The reactor did not lose its activity even after pumping through it a solution of substrate equaling 1,000 reactor volumes. This enzymatic reactor was also used for the transesterification of triacylglycerides from soybean oil to fatty acid methyl esters thus demonstrating the ability of the reactor to produce biodiesel. © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2008-11-12

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

  20. A novel nanoparticle formulation for sustained paclitaxel delivery.

    Science.gov (United States)

    Trickler, W J; Nagvekar, A A; Dash, A K

    2008-01-01

    To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC(50) of PTX. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

  1. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Rajan Rajabalaya

    2016-08-01

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

  2. Development and validation of a thin-layer chromatography method for stability studies of naproxen

    International Nuclear Information System (INIS)

    Rodriguez Hernandez, Yaslenis; Suarez Perez, Yania; Garcia Pulpeiro, Oscar; Rodriguez Borges, Tania

    2011-01-01

    The validation of an analytical method was carried out to be applied to the stability studies of the future formulations of naproxen suppositories for infant and adult use. The factors which mostly influenced in the naproxen stability were determined, the major degradation occurred in oxidizing acid medium and by action of light. The possible formation of esters between the free carboxyl group present in naproxen and the glyceryl monoestereate present in the base was identified as one of the degradation paths in the new formulation. The results were satisfactory. A thin-layer chromatography-based method was developed as well as the best chromatographic conditions were selected. GF 254 silica gel plates and ultraviolet developer at 254 nm were employed. Three solvent systems were evaluated of which A made up of glacial acetic: tetrahydrofurane:toluene (3:9:90 v/v/v)allowed adequate resolution between the analyte and the possible degradation products, with detection limit of 1 μg. The use of the suggested method was restricted to the identification of possible degradation products just for qualitative purposes and not as final test. The method proved to be sensitive and selective enough to be applied for the stated objective, according to the validation results

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    Graphical abstract: α-Tocopherol inhibits the oxidation of ·CH 3 to ·OCH 3 . Display Omitted Highlights: → α-Tocopherol does not inhibit the oxidation of DMSO to ·CH 3 . → α-Tocopherol inhibits the oxidation of ·CH 3 to ·OCH 3 . → α-Tocopherol does not inhibit the oxidation of PBN. → The structures of observed spin adducts were theoretically confirmed. - Abstract: 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.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. (paper)

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

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

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

    2015-02-20

    The current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size ∼ 71 μm) lactose particles with smooth surface containing mixture of α and β-lactose was recovered from gel, however percentage of α-lactose was more as compared to β-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose® ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

    Science.gov (United States)

    Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

    2014-12-01

    The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

  8. Comparison of spray congealing and melt emulsification methods for the incorporation of the water-soluble salbutamol sulphate in lipid microparticles.

    Science.gov (United States)

    Scalia, Santo; Traini, Daniela; Young, Paul M; Di Sabatino, Marcello; Passerini, Nadia; Albertini, Beatrice

    2013-02-01

    Salbutamol sulphate is widely used as bronchodilator for the treatment of asthma. Its use is limited by the relatively short duration of action and hence sustained delivery of salbutamol sulphate offers potential benefits to patients. This study explores the preparation of lipid microparticles (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate. The LMs were produced using different lipidic materials and surfactants, by classical melt emulsification-based methods (oil-in-water and water-in-oil-in-water emulsions) and the spray congealing technique. For the LMs obtained by melt emulsification a lack of release modulation was observed. On the other hand, the sustained release of salbutamol sulphate was achieved with glyceryl behenate microparticles prepared by spray congealing. These LMs were characterized by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. The drug loading was 4.72% (w/w). The particle size distribution measured by laser diffraction and electrical zone sensing was represented by a volume median diameter (Dv(50)) of 51.7-71.4 µm. Increasing the atomization air pressure from 4 to 8 bar produced a decrease of the Dv(50) to 12.7-17.5 µm. Incorporation of the hydrophilic salbutamol sulphate into LMs with sustained release characteristics was achieved by spray congealing.

  9. Effect of Liquid Crystalline Systems Containing Antimicrobial Compounds on Infectious Skin Bacteria.

    Science.gov (United States)

    Souza, Carla; Watanabe, Evandro; Aires, Carolina Patrícia; Lara, Marilisa Guimarães

    2017-08-01

    This study aimed (i) to prepare liquid crystalline systems (LCS) of glyceryl monooleate (GMO) and water containing antibacterial compounds and (ii) to evaluate their potential as drug delivery systems for topical treatment of bacterial infections. Therefore, LCS containing CPC (cetylpyridinium chloride) (LCS/CPC) and PHMB (poly(hexamethylene biguanide) hydrochloride) (LCS/PHMB) were prepared and the liquid crystalline phases were identified by polarizing light microscopy 24 h and 7 days after preparation. The in vitro drug release profile and in vitro antibacterial activity of the systems were assessed using the double layer agar diffusion method against Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Escherichia coli, and Enterococcus faecalis. The interaction between GMO and the drugs was evaluated by a drug absorption study. Stable liquid crystalline systems containing CPC and PHMB were obtained. LCS/PHMB decreased the PHMB release rate and exerted strong antibacterial activity against all the investigated bacteria. In contrast, CPC interacted with GMO so strongly that it became attached to the system; the amount released was not sufficient to exert antibacterial activity. Therefore, the studied liquid crystalline systems were suitable to deliver PHMB, but not CPC. Accordingly, it was demonstrated that GMO interacts with each drug differently, which may interfere in the final efficiency of GMO/water LCS.

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

    Directory of Open Access Journals (Sweden)

    Maria Iorizzi

    2008-06-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

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

    Science.gov (United States)

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

    2012-02-01

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

  14. Long-term stability investigation of o/w cosmetic creams stabilized by mixed emulsifier

    Directory of Open Access Journals (Sweden)

    Đekić Ljiljana M.

    2012-01-01

    Full Text Available Polyglyceryl-3 Methylglucose Distearate (PMD, TEGO® Care 450, Evonik, Germanyis natural (vegetable, non-ionic, PEG-free emulsifier, suitable for the formulation of oil-in-water (o/w cosmetic creams and lotions. The oil phase components can be selected from mineral oils, vegetable oils and synthetic esters, which enable different variety of application profile of these emulsions. It is possible to prepare stable emulsions using low-level concentration of the PMD (2-3% if lotions contain 10-25%, and creams 20-40 % of oil phase. PMD forms liquid crystal structure in the presence of stearic acid, glyceryl stearate, fatty alcohols, or their combinations. The o/w type creams, stabilized by these mixed emulsifiers are complex, multiphase systems. The aim of this work was to formulate, prepare and investigate long-term stability of the o/w creams stabilized by mixed emulsifier polyglyceryl-3 methylglucose distearate/glyceryl stearate/stearyl alcohol, depending on concentration levels of PMD (2% or 3% and oil:water phase ratio (20:80 and 30:70. The samples were prepared using hot/hot procedure. Organoleptic inspection, centrifugation test, rheological measurements, electric conductivity and pH value measurements were performed 72 h, 1, 3, 12 and 30 months after preparation. The prepared samples were apparently white and homogenous creams. The consistency and homogeneity were preserved after centrifugation of the creams after 72 h, 1, 3, 12 and 30 months storage, and no phase separation could be detected. The pH values obtained are suitable for skin application. Conductivity values (25.2-63.7 μS cm1, 72 h after preparation were attributed to the multiple phase o/w emulsions with high percentages of fixed water. Results of the rheological measurements have shown that the investigated creams exhibited non-Newtonian thyxotropic behavior. The concentration of emulsifier PMD and oil phase content had an influence on the rheological parameters of investigated

  15. Heterologous gene expression driven by carbonic anhydrase gene promoter in Dunaliella salina

    Science.gov (United States)

    Yurong, Chai; Yumin, Lu; Tianyun, Wang; Weihong, Hou; Lexun, Xue

    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.

  16. The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3.

    Science.gov (United States)

    Sims, K B; Lebo, R V; Benson, G; Shalish, C; Schuback, D; Chen, Z Y; Bruns, G; Craig, I W; Golbus, M S; Breakefield, X O

    1992-05-01

    Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.

  17. Multiyear nutrient removal performance of three constructed wetlands intercepting tile drain flows from grazed pastures.

    Science.gov (United States)

    Tanner, Chris C; Sukias, James P S

    2011-01-01

    Subsurface tile drain flows can be a major s ource of nurient loss from agricultural landscapes. This study quantifies flows and nitrogen and phosphorus yields from tile drains at three intensively grazed dairy pasture sites over 3- to 5-yr periods and evaluates the capacity of constructed wetlands occupying 0.66 to 1.6% of the drained catchments too reduce nutrient loads. Continuous flow records are combined with automated flow-proportional sampling of nutrient concentrations to calculate tile drain nutrient yields and wetland mass removal rates. Annual drainage water yields rangedfrom 193 to 564 mm (16-51% of rainfall) at two rain-fed sites and from 827 to 853 mm (43-51% of rainfall + irrigation) at an irrigated site. Annually, the tile drains exported 14 to 109 kg ha(-1) of total N (TN), of which 58 to 90% was nitrate-N. Constructed wetlands intercepting these flows removed 30 to 369 gTN m(-2) (7-63%) of influent loadings annually. Seasonal percentage nitrate-N and TN removal were negatively associated with wetland N mass loadings. Wetland P removal was poor in all wetlands, with 12 to 115% more total P exported annually overall than received. Annually, the tile drains exported 0.12 to 1.38 kg ha of total P, of which 15 to 93% was dissolved reactive P. Additional measures are required to reduce these losses or provide supplementary P removal. Wetland N removal performance could be improved by modifying drainage systems to release flows more gradually and improving irrigation practices to reduce drainage losses.

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

    Directory of Open Access Journals (Sweden)

    Marilene Estanqueiro

    2014-09-01

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

  19. Encapsulation of the UV filters ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane in lipid microparticles: effect on in vivo human skin permeation.

    Science.gov (United States)

    Scalia, S; Mezzena, M; Ramaccini, D

    2011-01-01

    Lipid microparticles loaded with the UVB filter ethylhexyl methoxycinnamate (EHMC) and the UVA filter butyl methoxydibenzoylmethane (BMDBM) were evaluated for their effect on the sunscreen agent's percutaneous penetration. Microparticles loaded with EHMC or BMDBM were prepared by the melt emulsification technique using stearic acid or glyceryl behenate as lipidic material, respectively, and hydrogenate phosphatidylcholine as the surfactant. Nonencapsulated BMDBM and EHMC in conjunction with blank microparticles or equivalent amounts of the 2 UV filters loaded in the lipid microparticles were introduced into oil-in-water emulsions and applied to human volunteers. Skin penetration was investigated in vivo by the tape-stripping technique. For the cream with the nonencapsulated sunscreen agents, the percentages of the applied dose diffused into the stratum corneum were 32.4 ± 4.1% and 30.3 ± 3.3% for EHMC and BMDBM, respectively. A statistically significant reduction in the in vivo skin penetration to 25.3 ± 5.5% for EHMC and 22.7 ± 5.4% for BMDBM was achieved by the cream containing the microencapsulated UV filters. The inhibiting effect on permeation attained by the lipid microparticles was more marked (45-56.3% reduction) in the deeper stratum corneum layers. The reduced percutaneous penetration of BMDBM and EHMC achieved by the lipid microparticles should preserve the UV filter efficacy and limit potential toxicological risks. Copyright © 2011 S. Karger AG, Basel.

  20. {alpha}-Tocopherol impact on oxy-radical induced free radical decomposition of DMSO: Spin trapping EPR and theoretical studies

    Energy Technology Data Exchange (ETDEWEB)

    Jerzykiewicz, Maria, E-mail: Mariaj@wchuwr.pl [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland); Cwielag-Piasecka, Irmina; Witwicki, Maciej; Jezierski, Adam [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland)

    2011-05-26

    Graphical abstract: {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. Display Omitted Highlights: {yields} {alpha}-Tocopherol does not inhibit the oxidation of DMSO to {center_dot}CH{sub 3}. {yields} {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. {yields} {alpha}-Tocopherol does not inhibit the oxidation of PBN. {yields} The structures of observed spin adducts were theoretically confirmed. - Abstract: 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 {alpha}-tocopherol. Additionally, the mixtures of {alpha}-tocopherol with linolenic acid and glyceryl trilinoleate as well as bioglycerols (glycerol fractions from biodiesel production) were tested. {alpha}-Tocopherol inhibited oxidation of the main decomposition product of DMSO, {center_dot}CH{sub 3} to {center_dot}OCH{sub 3} but did not prevent the transformation process of N-t-butyl-{alpha}-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.

  1. Phosphorus NMR of isolated perfused morris hepatomas

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Science.gov (United States)

    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.

  3. Computational Models of the Gastrointestinal Environment. 2. Phase Behavior and Drug Solubilization Capacity of a Type I Lipid-Based Drug Formulation after Digestion.

    Science.gov (United States)

    Birru, Woldeamanuel A; Warren, Dallas B; Han, Sifei; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Chalmers, David K

    2017-03-06

    Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the gastrointestinal (GI) tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the GI microenvironment containing a digested triglyceride-based (Type I) drug formulation. Both the experimental and theoretical models consist of molecular species representing bile (glycodeoxycholic acid), digested triglyceride (1:2 glyceryl-1-monooleate and oleic acid), and water. We have characterized the phase behavior of the physical system using nephelometry, dynamic light scattering, and polarizing light microscopy and compared these measurements to phase behavior observed in multiple MD simulations. Using this model microenvironment, we have investigated the dissolution of the poorly water-soluble drug danazol experimentally using LC-MS and theoretically by MD simulation. The results show how the formulation lipids alter the environment of the GI tract and improve the solubility of danazol. The MD simulations successfully reproduce the experimental results showing the utility of MD in modeling the fate of drugs after digestion of lipid-based formulations within the intestinal lumen.

  4. Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration.

    Science.gov (United States)

    Eskinazi-Budge, Aaron; Manickavasagam, Dharani; Czech, Tori; Novak, Kimberly; Kunzler, James; Oyewumi, Moses O

    2018-05-30

    Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia that has attracted so much attention in bone regeneration based on its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy simvastatin-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

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

    Science.gov (United States)

    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. © 2013 Wiley Periodicals, Inc.

  6. QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

    Directory of Open Access Journals (Sweden)

    Sharvil Patil

    2017-11-01

    Full Text Available BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF, a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD approach (Factorial design was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10 h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability.

  7. Automated spectrophotometer for plutonium and uranium determination

    International Nuclear Information System (INIS)

    Jackson, D.D.; Hodgkins, D.J.; Hollen, R.M.; Rein, J.E.

    1975-09-01

    The automated spectrophotometer described is the first in a planned series of automated instruments for determining plutonium and uranium in nuclear fuel cycle materials. It has a throughput rate of 5 min per sample and uses a highly specific method of analysis for these elements. The range of plutonium and uranium measured is 0.5 to 14 mg and 1 to 14 mg, respectively, in 0.5 ml or less of solution with an option to pre-evaporate larger volumes. The precision of the measurements is about 0.02 mg standard deviation over the range corresponding to about 2 rel percent at the 1-mg level and 0.2 rel percent at the 10-mg level. The method of analysis involves the extraction of tetrapropylammonium plutonyl and uranyl trinitrate complexes into 2-nitropropane and the measurement of the optical absorbances in the organic phase at unique peak wavelengths. Various aspects of the chemistry associated with the method are presented. The automated spectrophotometer features a turntable that rotates as many as 24 samples in tubes to a series of stations for the sequential chemical operations of reagent addition and phase mixing to effect extraction, and then to a station for the absorbance measurement. With this system, the complications of sample transfers and flow-through cells are avoided. The absorbance measurement system features highly stable interference filters and a microcomputer that controls the timing sequence and operation of the system components. Output is a paper tape printout of three numbers: a four-digit number proportional to the quantity of plutonium or uranium, a two-digit number that designates the position of the tube in the turntable, and a one-digit number that designates whether plutonium or uranium was determined. Details of the mechanical and electrical components of the instrument and of the hardware and software aspects of the computerized control system are provided

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

    Directory of Open Access Journals (Sweden)

    Shen J

    2016-09-01

    Full Text Available Jinyang Shen,1 Jianping Bi,2 Hongli Tian,1 Ye Jin,1 Yuan Wang,3 Xiaolin Yang,4 Zhonglin Yang,1 Junping Kou,5 Fei Li1 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 2Shandong Provincial Traditional Chinese Medical Hospital & Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 3Traditional Chinese Medical Hospital of Pukou District, 4Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine, 5Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People’s Republic of China Background: Akebia saponin D (ASD exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS based on the drug–phospholipid complex technique was developed to improve the oral absorption of ASD.Methods: ASD–phospholipid complex (APC was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats.Results: The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in n-octanol. Peceol (Glyceryl

  9. Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus.

    Science.gov (United States)

    Andrews, Mónica; Leiva, Elba; Arredondo-Olguín, Miguel

    2016-09-01

    We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P1). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p1; compared to control group). It was also significantly related to inflammation. The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Characterization of domestic graywater and graywater solids.

    Science.gov (United States)

    Sievers, Jan Christian; Londong, Jörg

    2018-03-01

    The knowledge of loads and concentrations is fundamental for the design of graywater treatment units, but the data on the characteristics of graywater and in particular graywater solids are weak. As general design values regarding graywater treatment facilities are not available for Germany, the objective of this article is to elaborate the characteristics of graywater and graywater solids. This paper describes the results of six sampling campaigns carried out on graywater systems in the German cities Berlin, Lübeck and Kiel. All graywater samples were collected proportional to the flow and the graywater solids were gathered separately. The collected data include graywater volumes and characteristics regarding the organic pollution (chemical oxygen demand (COD), 5-day biochemical oxygen demand (BOD 5 )) and nutrients (total nitrogen (TN), total phosphorus (TP)). The graywater volume fluctuated depending on the location. The specific average flow was 68 litre per inhabitant per day (L/inh.d). Inhabitant-specific loads of 49.3 gCOD t /inh·d, 28 gBOD 5 /inh.d, 1 gTN t /inh.d and 0.38 gTP t /inh.d (subscript 't' = total) were found. Information about the composition of graywater solids in terms of quantity and quality is seriously lacking. Therefore, graywater solids were examined with respect to organic matter (COD) and nutrients (TN, TP). The contribution of graywater solids with particle sizes over 200 microns in relation to the total inhabitant-specific load was approximately 3-8% depending on the parameter. The qualitative and quantitative characteristics of the investigated graywater fractions may serve as a base for the estimation of design values.

  11. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    Science.gov (United States)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    biocompatibility is a promising candidate for molecular receptor targeted MR imaging. Electronic supplementary information (ESI) available: FTIR data GTN-RT and GTN-500. See DOI: 10.1039/c1nr10591d

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

    Science.gov (United States)

    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. Langmuir and Langmuir-Blodgett films of multifunctional, amphiphilic polyethers with cholesterol moieties.

    Science.gov (United States)

    Reuter, Sascha; Hofmann, Anna M; Busse, Karsten; Frey, Holger; Kressler, Jörg

    2011-03-01

    Langmuir films of multifunctional, hydrophilic polyethers containing a hydrophobic cholesterol group (Ch) were studied by surface pressure-mean molecular area (π-mmA) measurements and Brewster angle microscopy (BAM). The polyethers were either homopolymers or diblock copolymers of linear poly(glycerol) (lPG), linear poly(glyceryl glycidyl ether) (lPGG), linear poly(ethylene glycol) (lPEG), or hyperbranched poly(glycerol) (hbPG). Surface pressure measurements revealed that the homopolymers lPG and hbPG did not stay at the water surface after spreading and solvent evaporation, in contrast to lPEG. Because of the incorporation of the Ch group in the polymer structure, stable Langmuir films were formed by Ch-lPG(n), Ch-lPGG(n), and Ch-hbPG(n). The Ch-hbPG(n), Ch-lPEG(n), Ch-lPEG(n)-b-lPG(m), Ch-lPEG(n)-b-lPGG(m), and Ch-lPEG(n)-b-hbPG(m) systems showed an extended plateau region assigned to a phase transition involving the Ch groups. Typical hierarchically ordered morphologies of the LB films on hydrophilic substrates were observed for all Ch-initiated polymers. All LB films showed that Ch of the Ch-initiated homopolymers is able to crystallize. This strong tendency of self-aggregation then triggers further dewetting effects of the respective polyether entities. Fingerlike morphologies are observed for Ch-lPEG(69), since the lPEG(69) entity is able to undergo crystallization after transfer onto the silicon substrate.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    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.

  18. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

    Science.gov (United States)

    Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

    2011-01-01

    The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X1), surfactant (X2), and drug/lipid ratio (X3) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was −8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release. PMID:21556343

  19. Survey of nuclear parameters from the TRIGA Mark I IPR R1 Brazilian reactor with concentric configuration aiming the application of K{sub 0} neutron activation technique; Levantamento de parametros nucleares do reator TRIGA Mark I IPR R1 com configuracao concentrica visando a aplicacao da tecnica de ativacao neutronica K{sub 0}

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Milton Batista

    2006-07-01

    This research intended to determine the nuclear parameters a, f, spectral index and neutron temperature in several irradiations positions of the TRIGA Mark 1 IPR-R1 reactor, for use on the parametric method K{sub 0} in the CDTN. K{sub 0} is a monostandard method of neutron activation analysis. It is, on the whole, experimentally simple, flexible and an important tool for accurate and convenient standardization in instrumental multi-element analysis. At the time the parameters were determined at the rotatory rack, lower layer and in the central thimble: alpha was calculated applying the three bare monitor method using {sup 197}Au, {sup 94}Zr and {sup 96}Zr; f determination was done according to the bare bi-isotopic method; neutron temperature was calculated through the direct method using {sup 176}Lu, {sup 94}Zr, {sup 96}Zr and {sup 197}Au and the Westcott's g(Tn) function for the {sup 176}Lu was calculated and the result was interpolated in the Grintakis and Kim (1975) Table, determining the neutron temperature. The procedure to check the parameters consisted in using standard solutions of Au (metal foil, NBS), Lu (LuO{sub 2}, Johnson Mattey Company - JMC) and Zr (ZrO{sub 2} and metal foil, Johnson Mattey Company 99,99% and Zry - 4: 98,14% of Zr, National Bureau of Standard- NBS). Several certified reference materials and two samples of intercomparisons (samples of sediment of the IAEA/ARCAL XXVI project) have been analysed by means of k{sub 0}- INAA in order to verify the efficiency of the method and the quality of the parameters. The certified reference materials were: GXR-2, GXR-5 and GXR-6 of the United States Geological Survey (USGS) and Soil-5, Soil-7 and SL-1 of the International Atomic Energy Agency (IAEA). (author)

  20. NORPERM, the Norwegian Permafrost Database - a TSP NORWAY IPY legacy

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

  2. Impact Of Elastic Modulus Degradation On Springback In Sheet Metal Forming

    International Nuclear Information System (INIS)

    Halilovic, Miroslav; Stok, Boris; Vrh, Marko

    2007-01-01

    Strain recovery after removal of forming loads, commonly defined as springback, is of great concern in sheet metal forming, in particular with regard to proper prediction of the final shape of the part. To control the problem a lot of work has been done, either by minimizing the springback on the material side or by increasing the estimation precision in corresponding process simulations. Unfortunately, by currently available software springback still cannot be adequately predicted, because most analyses of springback are using linear, isotropic and constant Young's modulus and Poisson's ratio. But, as it was measured and reported, none of it is true. The aim of this work is to propose an upgraded mechanical model which takes evolution of damage and related orthotropic stiffness degradation into account. Damage is considered by inclusion of ellipsoidal cavities, and their influence on the stiffness degradation is taken in accordance with the Mori-Tanaka theory, adopting the GTN model for plastic flow. In order to improve the numerical springback prediction, two major things are important: first, the correct evaluation of the stress-strain state at the end of the forming process, and second, correctness of the elastic properties used in the elastic relaxation analysis. Since in modelling of the forming process we adopt a damage constitutive model with orthotropic stiffness degradation considered, a corresponding damage parameters identification upon specific experimental tests data must be performed first, independently of the metal forming modelling. An improved identification of material parameters, which simultaneously considers tensile test results with different type of specimens and using neural network, is proposed. With regard to the case in which damage in material is neglected it is shown in the article how the springback of a formed part differs, when we take orthotropic damage evolution into consideration

  3. Survey of nuclear parameters from the TRIGA Mark I IPR R1 Brazilian reactor with concentric configuration aiming the application of K0 neutron activation technique

    International Nuclear Information System (INIS)

    Franco, Milton Batista

    2006-01-01

    This research intended to determine the nuclear parameters a, f, spectral index and neutron temperature in several irradiations positions of the TRIGA Mark 1 IPR-R1 reactor, for use on the parametric method K 0 in the CDTN. K 0 is a monostandard method of neutron activation analysis. It is, on the whole, experimentally simple, flexible and an important tool for accurate and convenient standardization in instrumental multi-element analysis. At the time the parameters were determined at the rotatory rack, lower layer and in the central thimble: alpha was calculated applying the three bare monitor method using 197 Au, 94 Zr and 96 Zr; f determination was done according to the bare bi-isotopic method; neutron temperature was calculated through the direct method using 176 Lu, 94 Zr, 96 Zr and 197 Au and the Westcott's g(Tn) function for the 176 Lu was calculated and the result was interpolated in the Grintakis and Kim (1975) Table, determining the neutron temperature. The procedure to check the parameters consisted in using standard solutions of Au (metal foil, NBS), Lu (LuO 2 , Johnson Mattey Company - JMC) and Zr (ZrO 2 and metal foil, Johnson Mattey Company 99,99% and Zry - 4: 98,14% of Zr, National Bureau of Standard- NBS). Several certified reference materials and two samples of intercomparisons (samples of sediment of the IAEA/ARCAL XXVI project) have been analysed by means of k 0 - INAA in order to verify the efficiency of the method and the quality of the parameters. The certified reference materials were: GXR-2, GXR-5 and GXR-6 of the United States Geological Survey (USGS) and Soil-5, Soil-7 and SL-1 of the International Atomic Energy Agency (IAEA). (author)

  4. The Gestational Trophoblastic Diseases: A Ten Year Retrospective Study

    Directory of Open Access Journals (Sweden)

    Razieh Mohammadjafari

    2010-01-01

    Full Text Available Background: Gestational trophoblastic disease (GTD defines a heterogenenous group ofinterrelated lesions that arise from the trophoblastic epithelium of the placenta. There are severalhistologically distinct types of GTD: hydatiform mole (complete or partial, persistant/invasivegestational trophoblastic neoplasia (GTN, choriocarcinoma and placenta site trophoblastictumors. The aim of this study was to determine the frequency and risk factors of GTD amongwomen admitted to Imam Khomeini Hospital in Ahvaz, Iran.Materials and Methods: This was a cross-sectional study conducted at Imam KhomeiniHospital in Ahvaz, Iran. All hospital records related to GTD (132 from 1996 until 2006 werereviewed. Demographic and histo-pathologic characteristics were extracted. Chi-square andFisher-exact tests were used to analyze all variables. P ≤ 0.05 was considered statisticallysignificant. SPSS, version 11 was used for statistical analysis.Results: The mean age of patients was 27.6 years. Most patients who presented with GTDwere of ages 18-35 years (71.3%. There was no relationship between age and hydatiformmole during the reproductive years. There were 28 (18.9% patients over the age 40, of which18 (15.90% of these had a complete hydatiform mole. Within this group, 9 (6.8% changedto a persistent mole. There was a significant relationship between age over 40 and completemole (p<0.02. The percentage of patients with blood groups A and O was the same (37.9%.There was a significant relationship between blood groups (O+ and A+ and complete mole(p<0.05.Conclusion: The most common age range for hydatiform mole was 18-35 years. Women overthe age of 40 had a more complete hydatiform mole, which is similar to the other countries.Age and blood group are two risk factors for hydatiform mole.

  5. North American Contact Dermatitis Group patch test results: 2009 to 2010.

    Science.gov (United States)

    Warshaw, Erin M; Belsito, Donald V; Taylor, James S; Sasseville, Denis; DeKoven, Joel G; Zirwas, Matthew J; Fransway, Anthony F; Mathias, C G Toby; Zug, Kathryn A; DeLeo, Vincent A; Fowler, Joseph F; Marks, James G; Pratt, Melanie D; Storrs, Frances J; Maibach, Howard I

    2013-01-01

    Patch testing is an important diagnostic tool for determination of substances responsible for allergic contact dermatitis. This study reports the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2009, to December 31, 2010. At 12 centers in North America, patients were tested in a standardized manner with a screening series of 70 allergens. Data were manually verified and entered into a central database. Descriptive frequencies were calculated, and trends were analyzed using χ2 statistics. A total of 4308 patients were tested. Of these, 2614 (60.7%) had at least 1 positive reaction, and 2284 (46.3%) were ultimately determined to have a primary diagnosis of allergic contact dermatitis. Four hundred twenty-seven (9.9%) patients had occupationally related skin disease. There were 6855 positive allergic reactions. As compared with the previous reporting period (2007-2008), the positive reaction rates statistically decreased for 20 allergens (nickel, neomycin, Myroxylon pereirae, cobalt, formaldehyde, quaternium 15, methydibromoglutaronitrile/phenoxyethanol, methylchlorisothiazolinone/methylisothiazolinone, potassium dichromate, diazolidinyl urea, propolis, dimethylol dimethylhydantoin, 2-bromo-2-nitro-1,3-propanediol, methyl methacrylate, ethyl acrylate, glyceryl thioglycolate, dibucaine, amidoamine, clobetasol, and dimethyloldihydroxyethyleneurea; P < 0.05) and statistically increased for 4 allergens (fragrance mix II, iodopropynyl butylcarbamate, propylene glycol, and benzocaine; P < 0.05). Approximately one quarter of tested patients had at least 1 relevant allergic reaction to a non-NACDG allergen. Hypothetically, approximately one quarter of reactions detected by NACDG allergens would have been missed by TRUE TEST (SmartPractice Denmark, Hillerød, Denmark). These results affirm the value of patch testing with many allergens.

  6. A nanostructured liquid crystalline formulation of 20(S)-protopanaxadiol with improved oral absorption.

    Science.gov (United States)

    Jin, Xin; Zhang, Zhen-Hai; Li, Song-Lin; Sun, E; Tan, Xiao-Bin; Song, Jie; Jia, Xiao-Bin

    2013-01-01

    As with many other anti-cancer agents, 20(S)-protopanaxadiol (PPD) has a low oral absorption. In this study, in order to improve the oral bioavailability of PPD, the cubic nanoparticles that it contains were used to enhance absorption. Therefore, the cubic nanoparticle loaded PPD were prepared through the fragmentation of the glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and were verified by transmission electron microscope, small angle X-ray scattering and differential scanning calorimetry. The in vitro release of 20(S)-protopanaxadiol from these nanoparticles was less than 5% at 12h. And then Caco-2 cell monolayer model was used to evaluate the absorption of PPD in vitro. Meanwhile the rat intestinal perfusion model and bioavailability were also estimated in vivo. The results showed that, in the Caco-2 cell model, the PPD-cubosome could increase the permeability values from the apical (AP) to the basolateral (BL) of PPD at 53%. The result showed that the four-site rat intestinal perfusion model was consistent with the Caco-2 cell model. And the result of a pharmacokinetic study in rats showed that the relative bioavailability of the PPD-cubosome (AUC(0-∞)) compared with the raw PPD (AUC(0-∞)) was 169%. All the results showed that the PPD-cubosome enhanced bioavailability was likely due to the increased absorption by the cubic nanoparticles rather than by the improved release. Hence, the cubic nanoparticles may be a promising oral carrier for the drugs that have a poor oral absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Multifunctional nanoparticles for prostate cancer therapy.

    Science.gov (United States)

    Chandratre, Shantanu S; Dash, Alekha K

    2015-02-01

    The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.

  8. Preparation and Oxidation Stability Evaluation of Tea Polyphenols-Loaded Inverse Micro-Emulsion.

    Science.gov (United States)

    Lan, Xiaohong; Sun, Jingjing; Yang, Ying; Chen, Mengjie; Liu, Jianhua; Wu, Jinhong; Wang, Zhengwu

    2017-05-01

    Compared to synthetic antioxidants, tea polyphenols (TPs) has its own advantages in edible oil industry, however, the hydrophilic properties have restricted its applications. In this study, the ternary phase diagram of TPs-loaded micro-emulsion (ME) system was constructed, in which glyceryl monooleate (GMO), Tween80, linoleic acid as the surfactants, ethanol as the co-surfactant and soybean, corn, sunflower oil as the oil phase, have been used for the preparation of ME. The results indicated that a composition of ME (57.5% oil, 18% Tween80, 18% GMO, 4% Linolic acid, and 2.5% water+ethanol) could dissolve maximum water and could stable for 2 mo at room temperature with an average diameter of 6 to 7 nm, as detected by means of dynamic light scattering (DLS). The loaded of TPs into ME led to an increase of particle size to 15 to 16 nm, due to increased polarity of the water phase. The antioxidant capacity of TPs in ME was characterized by the peroxide value (POV) method. The addition of 1% water phase with 0.1 g/mL TPs could retain the POV at low value for 30 d at accelerating temperature 50 °C. Meanwhile, comparing the three edible oil, ME with corn oil has lower conductivity and higher value of POV during the storage. This work provides an efficient and environmentally friendly approach for the preparation of TPs-loaded ME, which is beneficial to the application of TPs in edible oil. © 2017 Institute of Food Technologists®.

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

    Science.gov (United States)

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

    2012-05-30

    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Protective Effects of Butyrate-based Compounds on a Mouse Model for Spinal Muscular Atrophy

    Science.gov (United States)

    Butchbach, Matthew E. R.; Lumpkin, Casey J.; Harris, Ashlee W.; Saieva, Luciano; Edwards, Jonathan D.; Workman, Eileen; Simard, Louise R.; Pellizzoni, Livio; Burghes, Arthur H. M.

    2016-01-01

    Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analogue (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs—glyceryl tributyrate (BA3G) and VX563—on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favourable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID:26892876

  11. Non-invasive treatments of luteinizing hormone-releasing hormone for inducing spermiation in American (Bufo americanus) and Gulf Coast (Bufo valliceps) toads.

    Science.gov (United States)

    Rowson, Angela D.; Obringer, Amy R.; Roth, Terri L.

    2001-01-01

    As many as 20% of all assessed amphibian species are threatened with extinction, and captive breeding programs are becoming important components of conservation strategies for this taxon. For some species, exogenous hormone administration has been integrated into breeding protocols to improve propagation. However, most treatments are administered by an intraperitoneal injection that can be associated with some risks. The general goal of this study was to identify a non-invasive method of applying luteinizing hormone-releasing hormone (LHRH), which reliably induces sperm release in toads. Specific objectives were to 1) test the spermiation response after topical application of different LHRH doses to the abdominal seat region, 2) evaluate the effects of adding the absorption enhancers dimethyl sulfoxide (DMSO), acetone, and glyceryl monocaprylate (GMC) to the LHRH, 3) assess the spermiation response after oral delivery of LHRH in a mealworm vehicle, and 4) compare sperm characteristics and spermiation responses to treatments in two different toad species. Male American (n = 9) and Gulf Coast (n = 7) toads were rotated systematically through a series of treatments. Urine was collected and evaluated for the presence of sperm at 0, 3, 7, 12, and 24 hours post-treatment. There were no statistical differences in spermiation induction or sperm characteristics between American and Gulf Coast toads after the treatments. Oral administration of 100 &mgr;g LHRH was occasionally successful in inducing spermiation, but results appeared largely unreliable. Ventral dermal application of 100 or 10 &mgr;g LHRH in 40% DMSO were more effective (P Zoo Biol 20:63-74, 2001. Copyright 2001 Wiley-Liss, Inc.

  12. Post-anaesthetic myelomalacia in a horse : clinical communication

    Directory of Open Access Journals (Sweden)

    K.E. Joubert

    2005-06-01

    Full Text Available This article describes a rare neurological complication of anaesthesia in a 2 year-old Clydesdale colt undergoing castration. Anaesthesia was induced with glyceryl guaiacol ether and ketamine and maintained with halothane. Following an uneventful anaesthetic of 40 minutes, the horse recovered from anaesthesia in a padded recovery stall. After approximately 70 minutes in the recovery stall, the horse attempted to stand and adopted a dog sitting position. One hundred and fifty minutes later, the horse became distressed and was sedated with xylazine. Clinical examination of the horse did not reveal any evidence of myositis or fractures. A neurological examination revealed an intact anal reflex, deep pain response in the hind legs, tail tone and voluntary movement of the hind legs was possible. The horse deteriorated neurologically over the next 24 hours and was euthanased on humane grounds. The horse was submitted for necropsy. Gross pathology was unremarkable except for a small amount of haemorrhage around the right kidney. Histopathology revealed no abnormalities in any muscle groups or peripheral nerves. Congestion and axonal swelling of the spinal cord was evident from T16 to S1. Ischaemic neurons were evident from L 1 to L 6. The most prominent lesions were at L4 and L5. A diagnosis of myelomalacia was made. This is a rare complication of anaesthesia in horses with 9 case studies appearing in the literature since 1979. This is the 1st case to be reported in South Africa. The speculated pathophysiology and risk factors for this complication are discussed.

  13. Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity.

    Science.gov (United States)

    Taira, Norihisa; Katsuyama, Yushi; Yoshioka, Masato; Muraoka, Osamu; Morikawa, Toshio

    2018-04-10

    l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives ( 1 - 28 ) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure-function relationships. Although not the most potent inhibitors, 3- O -(2,3-dihydroxypropyl)-2- O -hexyl-l-ascorbic acid ( 6 , IC 50 = 81.4 µM) and 2- O -(2,3-dihydroxypropyl)-3- O -hexyl-l-ascorbic acid ( 20 , IC 50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3- O -alkyl-derivatives ( 2 - 14 ) exhibit stronger inhibitory activity than the corresponding 2- O -alkyl-derivatives ( 16 - 28 ); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.

  14. Multislice CT coronary angiography: effect of sublingual nitroglycerine on the diameter of coronary arteries

    International Nuclear Information System (INIS)

    Dewey, M.; Hamm, B.; Hoffmann, H.

    2006-01-01

    Purpose: to investigate the influence of sublingual glycerol trinitrate (1.2 mg, Nitrate [nitroglycerine], Nitrolingual N spray) on the coronary artery diameter on multislice computed tomography (MSCT) coronary angiography. Materials and methods: out of our database of patients who underwent MSCT (slice thickness of 0.5 mm, Aquilion, Toshiba) coronary angiography between July 2003 and November 2005 (950 patients) we retrospectively identified patients with follow-up examinations who received Nitrate for one examination while another examination was performed without Nitrate (10 patients). Another 10 patients who underwent two MSCT examinations with sublingual Nitrate administration were randomly selected from this database to serve as control group. For the resulting 40 MSCT examinations, blinded MSCT datasets were prepared, which were randomly evaluated by a reader blinded to the patient information and whether or not Nitrate had been given. The proximal coronary artery diameters were measured for the left main coronary artery (LMA), the left anterior descending coronary artery (LAD), the left circumflex coronary artery (LCX), and the right coronary artery (RCA) in all 40 datasets, resulting in altogether 160 measurements. Results: the proximal diameters of all four coronary arteries were significantly larger on the MSCT coronary angiograms obtained after sublingual administration of Nitrate compared with the examinations in the same 10 patients without Nitrate (p < 0.001). The average diameters without and with Nitrate for the LMA, LAD, LCX, and RCA were 4.3 ± 1.1 vs. 4.8 ± 0.9 mm (12% increase, p < 0.005), 3.0 ± 0.6 vs. 3.5 ± 0.5 mm (17% increase, p < 0.001), 2.7 ± 0.6 vs. 3.2 ± 0.7 mm (19% increase, p < 0.005), and 2.9 ± 0.9 vs. 3.5 ± 0.7 mm (21% increase, p < 0.005), respectively. In the control group of 10 patients who underwent two MSCT coronary angiographies after sublingual Nitrate, no significant difference in the proximal diameter of all four

  15. Evaluation and optimization of pH-responsive niosomes as a carrier for efficient treatment of breast cancer.

    Science.gov (United States)

    Salem, Heba F; Kharshoum, Rasha M; Abo El-Ela, Fatma I; F, Amr Gamal; Abdellatif, Khaled R A

    2018-02-27

    Tamoxifen citrate (TXC) is commonly indicated to prevent cell multiplication and development of breast cancer. However, it is usually associated with limited activity and development of toxicity and resistance. This study aimed to describe an in situ pH-responsive niosomes as a carrier for localized and sustained delivery of TXC. The thin film hydration method was utilized to produce TXC niosomes using sorbitan monostearate and cholesterol of 1:1 Molar ratio. The produced formula displayed nano-spherical shape with entrapment efficiency (EE) of 88.90 ± 0.72% and drug release of 49.2 ± 1.51% within 8 h. This formula was incorporated into chitosan/glyceryl monooleate (CH/GMO) as a localized in situ pH-responsive hydrogel delivery system. Different formulae were produced by Design-Expert software based on user-defined response surface design utilizing different chitosan concentration (A) and GMO concentration (B) characterized for mean viscosity (R 2 ) and in vitro release studies (R 1 ). The results displayed that R 1 was significantly antagonistic with both of A and B while R 2 was significantly synergistic with both of them. The optimum formula was selected and capped with gold as an ideal candidate for computed tomography (CT) to evaluate the efficacy and tissue distribution of TXC utilizing Ehrlich carcinoma mice model. The optimum formula showed localized TXC in a tumour and consequently a significant anti-tumour efficacy compared with free TXC. Based on these outcomes, the novel in situ pH-responsive TXC-loaded noisome could be a promising formula for the efficient treatment of breast cancer.

  16. Development and evaluation of exemestane-loaded lyotropic liquid crystalline gel formulations.

    Science.gov (United States)

    Musa, Muhammad Nuh; David, Sheba Rani; Zulkipli, Ihsan Nazurah; Mahadi, Abdul Hanif; Chakravarthi, Srikumar; Rajabalaya, Rajan

    2017-01-01

    Introduction: The use of liquid crystalline (LC) gel formulations for drug delivery has considerably improved the current delivery methods in terms of bioavailability and efficacy. The purpose of this study was to develop and evaluate LC gel formulations to deliver the anti-cancer drug exemestane through transdermal route. Methods: Two LC gel formulations were prepared by phase separation coacervation method using glyceryl monooleate (GMO), Tween 80 and Pluronic® F127 (F127). The formulations were characterized with regard to encapsulation efficiency (EE), vesicle size, Fourier transform infrared (FTIR) spectroscopy, surface morphology (using light and fluorescence microscopy), in vitro release, ex vivo permeation, in vitro effectiveness test on MDA-MB231 cancer cell lines and histopathological analysis. Results: Results exhibited that the EE was 85%-92%, vesicle size was 119.9-466.2 nm while morphology showed spherical vesicles after hydration. An FTIR result also revealed that there was no significant shift in peaks corresponding to Exemestane and excipients. LC formulations release the drug from cellulose acetate and Strat-MTM membrane from 15%-88.95%, whereas ex vivo permeation ranges from 37.09-63%. The in vitro effectiveness study indicated that even at low exemestane concentrations (12.5 and 25 μg/mL) the formulations were able to induce cancer cell death, regardless of the surfactant used. Histopathological analysis thinning of the epidermis as the formulations penetrate into the intercellular regions of squamous cells. Conclusion: The results conjectured that exemestane could be incorporated into LC gels for the transdermal delivery system and further preclinical studies such as pharmacokinetic and pharmacodynamic studies will be carried out with suitable animal models.

  17. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Directory of Open Access Journals (Sweden)

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  18. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    Directory of Open Access Journals (Sweden)

    Dezzutti Charlene

    2011-03-01

    Full Text Available Abstract 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.

  19. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

    Science.gov (United States)

    Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

    2014-03-15

    Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors. © 2013 UICC.

  20. Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells.

    Directory of Open Access Journals (Sweden)

    Patrick M Long

    Full Text Available Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA, the primary storage form of acetate in the brain, and aspartoacylase (ASPA, the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA, which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683 and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35 relative to an oligodendrocyte progenitor line (Oli-Neu were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation.

  1. The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

    Science.gov (United States)

    Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

    2017-08-01

    The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

  2. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride

    Directory of Open Access Journals (Sweden)

    Bharti Gaba

    2015-12-01

    Full Text Available The main aim of the present study was to develop and evaluate Terbinafine HCl (TH-loaded nanostructured lipid carrier (NLC for the treatment of fungal infection via topical administration. Fungal infections are tremendously widespread and the treatments are effective but associated toxicities restrict their use. TH-NLC was prepared using high pressure homogenization technique using Glyceryl Monostearate (GMS as solid lipid, Labrasol as liquid lipid and Pluronic F-127 as surfactant, binary lipid phase was selected in the ratio 6:4 w/w (solid:liquid lipid ratio. The mean diameter of optimized TH-NLCs was found to be 128 ± 4.5 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM and transmission electron microscopy (TEM analyses. The in vitro release studies showed 92.60 ± 0.87% drug release over 24 h as compared to the marketed formulation which showed only 82.826 ± 0.29%. Ex vivo skin permeation study showed about 86.35% permeation however from the marketed formulation it showed 69.41%. The pharmacodynamic studies indicated that TH-NLC (771 ± 41.797 CFUs gel efficiently reduced the fungal burden in shorter duration of time as compared to marketed formulation (1558 ± 140.524 CFUs and dispersion (95,582 ± 2316.619 CFUs (p value > 0.001. Therefore, it can be concluded that the developed NLCs showed a sustained release pattern and reduction of fungal burden in the infected area. Hence, TH-NLC could be a potential alternative for treatment of topical fungal infection after clinical evaluation in near future.

  3. A multi-scale correlative investigation of ductile fracture

    International Nuclear Information System (INIS)

    Daly, M.; Burnett, T.L.; Pickering, E.J.; Tuck, O.C.G.; Léonard, F.; Kelley, R.; Withers, P.J.; Sherry, A.H.

    2017-01-01

    The use of novel multi-scale correlative methods, which involve the coordinated characterisation of matter across a range of length scales, are becoming of increasing value to materials scientists. Here, we describe for the first time how a multi-scale correlative approach can be used to investigate the nature of ductile fracture in metals. Specimens of a nuclear pressure vessel steel, SA508 Grade 3, are examined following ductile fracture using medium and high-resolution 3D X-ray computed tomography (CT) analyses, and a site-specific analysis using a dual beam plasma focused ion beam scanning electron microscope (PFIB-SEM). The methods are employed sequentially to characterise damage by void nucleation and growth in one volume of interest, allowing for the imaging of voids that ranged in size from less than 100 nm to over 100 μm. This enables the examination of voids initiated at carbide particles to be detected, as well as the large voids initiated at inclusions. We demonstrate that this multi-scale correlative approach is a powerful tool, which not only enhances our understanding of ductile failure through detailed characterisation of microstructure, but also provides quantitative information about the size, volume fractions and spatial distributions of voids that can be used to inform models of failure. It is found that the vast majority of large voids nucleated at MnS inclusions, and that the volume of a void varied according to the volume of its initiating inclusion raised to the power 3/2. The most severe voiding was concentrated within 500 μm of the fracture surface, but measurable damage was found to extend to a depth of at least 3 mm. Microvoids associated with carbides (carbide-initiated voids) were found to be concentrated around larger inclusion-initiated voids at depths of at least 400 μm. Methods for quantifying X-ray CT void data are discussed, and a procedure for using this data to calibrate parameters in the Gurson-Tvergaard Needleman (GTN

  4. Regional Resource Planning Study

    International Nuclear Information System (INIS)

    2001-01-01

    PG and E GTN. 7 tabs., 26 figs

  5. EFEITO DO TREINO NEUROMUSCULAR NA ROTAÇÃO DO JOELHO DURANTE A ATERRISSAGEM EM MULHERES

    Directory of Open Access Journals (Sweden)

    Narayana Vianna Spanó

    2016-04-01

    Full Text Available Introdução: O grande índice de lesões do ligamento cruzado anterior sem envolver contato em mulheres é motivo de curiosidade entre os cientistas, pois avaliações de aterrissagem podem sugerir a predisposição ao risco dessa lesão. Neste sentido, vários protocolos de treinamento foram utilizados como intervenção e obtiveram resultados diversificados na alteração desse fator de risco. Objetivo: O objetivo deste projeto foi avaliar as possíveis alterações de rotação do joelho na aterrissagem unipodal após a intervenção de um programa de treinamento neuromuscular. Métodos: Participaram do estudo 18 mulheres com idade entre 18 e 51 anos, que foram distribuídas em dois grupos: grupo de treinamento neuromuscular de oito semanas (GTN (n = 11 e grupo controle (GC (n = 7. Além disso, não apresentavam lesão musculoesquelética ou dores nos membros inferiores. Cada participante realizou cinco aterrissagens unipodais válidas de uma plataforma de 40 cm de altura. O processo de captura de movimento foi realizado com 12 câmeras infravermelho do sistema OptiTrack(tm para obter as coordenadas tridimensionais de marcadores fixados nos pontos anatômicos de interesse. Os sistemas de coordenadas locais da coxa e da perna foram definidos por meio dos respectivos marcadores fixados nos pontos anatômicos. Dessa forma, foram calculados os ângulos de rotação do joelho nos planos sagital, frontal e transverso através das sequências dos ângulos de Euler e as velocidades angulares através das formulações dos quatérnions. Resultados: Os resultados mostraram que houve um aumento na velocidade de rotação do joelho após o treinamento neuromuscular. Conclusão: Conclui-se que o treinamento neuromuscular resultou em maior velocidade de rotação no joelho nos 40 milissegundos que sucedem a aterrissagem unipodal.

  6. A short history of nitroglycerine and nitric oxide in pharmacology and physiology.

    Science.gov (United States)

    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.

  7. Acetate supplementation reduces microglia activation and brain interleukin-1β levels in a rat model of Lyme neuroborreliosis

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    Brissette Catherine A

    2012-11-01

    Full Text Available Abstract Background We have found that acetate supplementation significantly reduces neuroglia activation and pro-inflammatory cytokine release in a rat model of neuroinflammation induced with lipopolysaccharide. To test if the anti-inflammatory effect of acetate supplementation is specific to a TLR4-mediated injury, we measured markers of neuroglia activation in rats subjected to B. burgdorferi-induced neuroborreliosis that is mediated in large part by a TLR2-type mechanism. Methods In this study, rats were subjected to Lyme neuroborreliosis following an intravenous infusion of B. burgdorferi (B31-MI-16. Acetate supplementation was induced using glyceryl triacetate (6g/kg by oral gavage. Immunohistochemistry, qPCR, and western blot analyses were used to measure bacterial invasion into the brain, neuroglial activation, and brain and circulating levels of interleukin 1β. Statistical analysis was performed using one-way analysis of variance (ANOVA followed by a Tukey’s post hoc tests or using a Student’s t test assuming unequal variances when appropriate. Results We found that acetate supplementation significantly reduced microglia activation by 2-fold as determined by immunohistochemical and western blot analysis. Further, acetate supplementation also reduced the expression of the pro-inflammatory cytokine IL-1β by 2-fold as compared to controls. On the other hand, the inoculation of rats with B. burgdorferi had no effect on astroglial activation as determined by immunocytochemistry and western blot analysis despite significant increases in circulation levels of antigen toward B. burgdorferi and presence of the bacteria in the central nervous system. Conclusions These results suggest that microglial activation is an essential component to neuroborreliosis and that acetate supplementation may be an effective treatment to reduce injury phenotype and possibly injury progression in Lyme neuroborreliosis.

  8. A mucoadhesive in situ gel delivery system for paclitaxel.

    Science.gov (United States)

    Jauhari, Saurabh; Dash, Alekha K

    2006-06-02

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

  9. Vitamin E TPGS emulsified vinorelbine bitartrate loaded solid lipid nanoparticles (SLN): Formulation development, optimization and in vitro characterization.

    Science.gov (United States)

    Maurya, Lakshmi; Rajamanickam, Vijayakumar Mahalingam; Narayan, Gopeshwar; Singh, Sanjay

    2018-04-08

    Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for breast cancer, has been proved to beneficial as first line and subsequent therapies. However, it's hydrophilic and thermo labile nature provides hindrance to oral clinical translation. The current work focused on the application of DOE a modern statistical optimization tool for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising integrity and anticancer activity of the drug. SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array design with optimized formulation and process variables. The emulsifying nature and low melting point of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer activity by MTT assay on MCF-7 cancer cell lines. The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. In-vitro release studies showed biphasic release pattern following Korsemeyer peppas model with fickian release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5 and 18.5 fold more effective, respectively, compared to the pristine VRL. DOE approach was successfully applied for the development of VRL-SLNs. Enhanced entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS associated SLNs may be potential carrier in cancer chemotherapeutics. Copyright© Bentham Science Publishers; For any queries, please

  10. The efficacy of Isotretinoin-loaded solid lipid nanoparticles in comparison to Isotrex® on acne treatment

    Directory of Open Access Journals (Sweden)

    Shiva Golmohammadzadeh

    2013-01-01

    Full Text Available Abstract: Topical retinoids are considered as the first line therapy in the treatment of acne vulgaris, but they are associated with cutaneous irritation. In this study, isotretinoin-loaded solid lipid nanoparticles(IT-SLN were prepared to treat the mild to moderate acne. Also using IT-SLN would minimize IT adverse effects in comparison to commercial product, Isotrex®. This study was conducted to prepare and characterize IT-SLN and assessing the efficiency of IT-SLN comparing to Isotrex® acne. IT-SLN was prepared using hot high pressure homogenization method.  IT-SLN contained 0.05% IT in 5% of lipid phase (Glyceryl monostearate- GMS and tween 80 (2.5 % w/v was used as surfactant in the aqueous phase. IT-SLN was characterized by particle size analyzing, differential scanning calorimetry and transmission electron microscopy. Encapsulation efficacy was also obtained using spectrophotometry. The efficacy of IT-SLN was evaluated in a randomized, single-blind, parallel-group study and compared with Isotrex®. Forty patients encountered in the study and divided in two groups. Treatment regimen was once-nightly topical administration accompanied with topical administration of clindamycin 2% solution twice a day for 8 weeks. The particle size of IT-SLN was around 60 nm with PDI of 0.4 and zeta potential was about -40 mV. Encapsulation efficacy of IT in SLN in crystalline form was 84±0.21%. IT-SLN produced significantly better treatment than Isotrex® in both non-inflammatory and inflammatory lesions according to its recovery percent after 8 weeks. Also IT-SLN gained better global assessment scores. Our results showed that IT-SLN had higher efficacy than Isotrex® to clear non-inflammatory and inflammatory lesions.

  11. Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil.

    Science.gov (United States)

    Rajinikanth, Paruvathanahalli Siddalingam; Chellian, Jestin

    The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol ® ATO 5 (glyceryl palmitostearate) and Labrasol ® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol ® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol ® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm 2 /h) as compared with plain 5-FU gel (2.85±1.12 μg/cm 2 /h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm 2 ) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm 2 ) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

  12. Immune system modulation in the central nervous system: A possible role for endocannabinoids

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2007-01-01

    The immune system is designed to protect the body from infection and tumor formation. To perform this function, cells of the immune system can be dangerous for the survival and function of the neuronal network in the brain under the influence of infection or immune imbalance. An attack of immune cells inside the brain includes the potential for severe neuronal damage or cell death and therefore impairment of the CNS function. To avoid such undesirable action of the immune system, the CNS performs a cascade of cellular and molecular mechanisms enabling strict control of immune reactions i mmune privilege . Under inflammatory and patholological conditions, uncontrolled immune system results in the activation of neuronal damage that is frequently associated with neurological diseases. On the other hand, processes of neuroprotection and neurorepair after neuronal damage depend on a steady and tightly controlled immunesurvelliance. Many immunoprotectants play a role to imbalance the immune reactions in the CNS and other organs which presents an important therapeutic target. It has been reported recently that endocannabinoids are secreted in abundance in the CNS following neuronal insult, probably for its protection. There are at least two types of cannabinoid receptors, CB1 and CB2. Both are coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. Endogenous agonists for cannabinoid receptors (endocannabinoids), have been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol (2AG), and 2-archidonyl glyceryl ether. Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. Therapeutic uses of cannabinoid receptor agonists/antagonists include the management of many disease conditions. They are also involved in immune system suppression and in cell to cell communication

  13. Cubic liquid crystalline nanoparticles containing a polysaccharide from Ulva fasciata with potent antihyperlipidaemic activity

    Directory of Open Access Journals (Sweden)

    Azza A. Matloub

    2018-02-01

    Full Text Available The present study involves the preparation of cubic liquid crystalline nanoparticles (cubsomes for liver targeting to assess the potential of a formulated bioactive polysaccharide isolated from the hot aqueous extract of Ulva fasciata as an alternative natural agent with anti-hyperlipidaemic activity. Cubosomal nanoparticles were prepared by disrupting the cubic gel phase of the polysaccharide and water in the presence of a surfactant. Different lipid matrices and stabilizers were tested. All the formulations were in the nanosize range and showed sufficient negative charge to inhibit the aggregation of the cubosomes. Drug entrapment efficiencies (EEs% were determined and in vitro release studies were performed. Transmission electron microscopy (TEM and differential scanning calorimetry were used to analyze the loaded cubosomal nanoparticles containing glyceryl monostearate (GMO 2.25 g, poloxamer 407 (0.25 g and 50 mg of the polysaccharide. A preclinical study comparing the cubic liquid crystalline nanoparticles containing polysaccharide to fluvastatin as a reference drug in hyperlipidaemic rats was conducted. The rats treated with the polysaccharide- loaded cubosomes showed significant decreases in total cholesterol (TC, triglycerides (TG and total lipid (TL compared to the untreated HL rats. In addition, oxidative stress and antioxidant biomarkers were measured in the HL rats. Compared to the untreated HL rats, the cubosome treated rats showed a significant reduction in malondialdehyde (MDA, whereas insignificant changes were detected in nitric oxide (NO, glutathione (GSH levels and total antioxidant capacity (TAC. Further, vascular and intercellular adhesion molecules (VCAM, ICAM, and myeloperoxidase were demonstrated. A histopathological examination was conducted to study the alterations in histopathological lesions and to document the biochemical results. In conclusion, this study demonstrates the superiority of using a natural lipid

  14. Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries- is epinephrine the culprit?

    Science.gov (United States)

    Jayamali, W D; Herath, H M M T B; Kulathunga, Aruna

    2017-09-04

    Anaphylaxis is an acute, potentially fatal medical emergency. Myocardial injury or infarction in the setting of an anaphylaxis can be due the anaphylaxis itself, when it is known as Kounis syndrome or it can also be due to the effect of epinephrine treatment. Epinephrine is considered as the cornerstone in management of anaphylaxis. Myocardial infarction secondary to therapeutic doses of adrenaline is a rare occurrence and only a few cases have been reported in literature. The mechanism of myocardial injury was considered to be due to coronary vasospasm secondary to epinephrine as the coronary angiograms were normal on these occasions. A 21-year- old previously healthy male got admitted to the local hospital with an urticarial rash and difficulty in breathing, one hour after ingestion of prawns for which he was known to be allergic. He was treated with 0.5 ml of intramuscular adrenaline (1:1000) which was administered to the lateral side of the thigh, following which he developed palpitations and tightening type central chest pain. Electrocardiogram showed ST segment depressions in leads III, aVF and V1 to V5 and he was transferred to a tertiary care hospital. The second electrocardiogram, done 2 h later, showed resolution of ST segment depressions but new T inversions in leads I and aVL. Troponin I was elevated with a titer of 2.15 ng/ml. He was treated with sublingual GTN in the emergency treatment unit and the symptoms resolved. Transthoracic 2D echocardiogram and stress testing with treadmill was normal and CT coronary angiogram revealed normal coronary arteries. Here we present a case of a young healthy adult with no significant risk factors for coronary artery disease who developed myocardial infarction following intramuscular administration of therapeutic dose of adrenalin for an anaphylactic reaction. The postulated mechanism is most likely an alpha receptor mediated coronary vascular spasm. However the use of adrenaline in the setting of life

  15. The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study.

    Science.gov (United States)

    Kulbacka, Julita; Pucek, Agata; Wilk, Kazimiera Anna; Dubińska-Magiera, Magda; Rossowska, Joanna; Kulbacki, Marek; Kotulska, Małgorzata

    2016-10-01

    Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of

  16. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control.

    Science.gov (United States)

    Lee, Brendan; Rhead, William; Diaz, George A; Scharschmidt, Bruce F; Mian, Asad; Shchelochkov, Oleg; Marier, J F; Beliveau, Martin; Mauney, Joseph; Dickinson, Klara; Martinez, Antonia; Gargosky, Sharron; Mokhtarani, Masoud; Berry, Susan A

    2010-07-01

    Glycerol phenylbutyrate (glyceryl tri (4-phenylbutyrate)) (GPB) is being studied as an alternative to sodium phenylbutyrate (NaPBA) for the treatment of urea cycle disorders (UCDs). This phase 2 study explored the hypothesis that GPB offers similar safety and ammonia control as NaPBA, which is currently approved as adjunctive therapy in the chronic management of UCDs, and examined correlates of 24-h blood ammonia. An open-label, fixed sequence switch-over study was conducted in adult UCD patients taking maintenance NaPBA. Blood ammonia and blood and urine metabolites were compared after 7 days (steady state) of TID dosing on either drug, both dosed to deliver the same amount of phenylbutyric acid (PBA). Ten subjects completed the study. Adverse events were comparable for the two drugs; 2 subjects experienced hyperammonemic events on NaPBA while none occurred on GPB. Ammonia values on GPB were approximately 30% lower than on NaPBA (time-normalized AUC=26.2 vs. 38.4 micromol/L; Cmax=56.3 vs. 79.1 micromol/L; not statistically significant), and GPB achieved non-inferiority to NaPBA with respect to ammonia (time-normalized AUC) by post hoc analysis. Systemic exposure (AUC(0-24)) to PBA on GPB was 27% lower than on NaPBA (540 vs. 739 microgh/mL), whereas exposure to phenylacetic acid (PAA) (575 vs. 596 microg h/mL) and phenylacetylglutamine (PAGN) (1098 vs. 1133 microg h/mL) were similar. Urinary PAGN excretion accounted for approximately 54% of PBA administered for both NaPBA and GPB; other metabolites accounted for <1%. Intact GPB was generally undetectable in blood and urine. Blood ammonia correlated strongly and inversely with urinary PAGN (r=-0.82; p<0.0001) but weakly or not at all with blood metabolite levels. Safety and ammonia control with GPB appear at least equal to NaPBA. Urinary PAGN, which is stoichiometrically related to nitrogen scavenging, may be a useful biomarker for both dose selection and adjustment for optimal control of venous ammonia. Copyright

  17. Topical Delivery of Erythromycin Through Cubosomes for Acne.

    Science.gov (United States)

    Khan, Sana; Jain, Poorva; Jain, Sourabh; Jain, Richa; Bhargava, Saurabh; Jain, Aakanchha

    2018-01-01

    Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Superhydrophilic surfaces from short and medium chain solvo-surfactants

    Directory of Open Access Journals (Sweden)

    Valentin Romain

    2013-01-01

    Full Text Available Pure monoglycerides (GM-Cs and glycerol carbonate esters (GCE-Cs are two families of oleochemical molecules composed of a polar part, glycerol for GM-Cs, glycerol carbonate for GCE-Cs, and a fatty acid lipophilic part. From a chemical point of view, GM-Cs include two free oxygen atoms in the hydroxyl functions and one ester function between the fatty acid and the glycerol parts. GCE-Cs contain two blocked oxygen atoms in the cyclic carbonate backbone and three esters functions: two endocyclic in the five-membered cyclic carbonate function, one exocyclic between the fatty acid and glycerol carbonate parts. At the physico-chemical level, GMCs and GCE-Cs are multifunctional molecules with amphiphilic structures: a common hydrophobic chain to the both families and a polar head, glycerol for GMs and glycerol carbonate for GCE-Cs. Physicochemical properties depend on chain lengths, odd or even carbon numbers on the chain, and glyceryl or cyclocarbonic polar heads. The solvo-surfactant character of GM-Cs and overall GCE-Cs were discussed through the measurements of critical micellar concentration (CMC or critical aggregation concentration (CAC. These surface active glycerol esters/glycerol carbonate esters were classified following their hydrophilic/hydrophobic character correlated to their chain length (LogPoctanol/water = f(atom carbon number. Differential scanning calorimetry and optical polarized light microscopy allow us to highlight the selfassembling properties of the glycerol carbonate esters alone and in presence of water. We studied by thermal analysis the polymorphic behaviour of GCE-Cs, and the correlation between their melting points versus the chain lengths. Coupling the self-aggregation and crystallization properties, superhydrophilic surfaces were obtained by formulating GM-Cs and GCE-Cs. An efficient durable water-repellent coating of various metallic and polymeric surfaces was allowed. Such surfaces coated by self-assembled fatty acid

  19. Semantic Data Integration and Ontology Use within the Global Earth Observation System of Systems (GEOSS) Global Water Cycle Data Integration System

    Science.gov (United States)

    Pozzi, W.; Fekete, B.; Piasecki, M.; McGuinness, D.; Fox, P.; Lawford, R.; Vorosmarty, C.; Houser, P.; Imam, B.

    2008-12-01

    The inadequacies of water cycle observations for monitoring long-term changes in the global water system, as well as their feedback into the climate system, poses a major constraint on sustainable development of water resources and improvement of water management practices. Hence, The Group on Earth Observations (GEO) has established Task WA-08-01, "Integration of in situ and satellite data for water cycle monitoring," an integrative initiative combining different types of satellite and in situ observations related to key variables of the water cycle with model outputs for improved accuracy and global coverage. This presentation proposes development of the Rapid, Integrated Monitoring System for the Water Cycle (Global-RIMS)--already employed by the GEO Global Terrestrial Network for Hydrology (GTN-H)--as either one of the main components or linked with the Asian system to constitute the modeling system of GEOSS for water cycle monitoring. We further propose expanded, augmented capability to run multiple grids to embrace some of the heterogeneous methods and formats of the Earth Science, Hydrology, and Hydraulic Engineering communities. Different methodologies are employed by the Earth Science (land surface modeling), the Hydrological (GIS), and the Hydraulic Engineering Communities; with each community employing models that require different input data. Data will be routed as input variables to the models through web services, allowing satellite and in situ data to be integrated together within the modeling framework. Semantic data integration will provide the automation to enable this system to operate in near-real-time. Multiple data collections for ground water, precipitation, soil moisture satellite data, such as SMAP, and lake data will require multiple low level ontologies, and an upper level ontology will permit user-friendly water management knowledge to be synthesized. These ontologies will have to have overlapping terms mapped and linked together. so

  20. RISK FACTORS FOR GESTATIONAL TROPHOBLASTIC NEOPLASIA: A CASE CONTROL STUDY IN A TERTIARY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Hema Sreedharan Nair

    2016-10-01

    Full Text Available BACKGROUND Gestational trophoblastic disease is a spectrum of proliferative abnormalities of the trophoblast. GTD represents a benign form of the disease while GTN is the malignant often metastatic lesion. 75-80 per cent of patients initially diagnosed as GTD will follow a benign course after dilatation and curettage. 15-20 per cent develop locally invasive disease and 3-5 per cent develop metastatic lesions. The study aims to assess the proportion of gestational trophoblastic neoplasia among women with gestational trophoblastic disease and identify the risk factors for chemotherapy in gestational trophoblastic neoplasia. MATERIALS AND METHODS This is a case-control study conducted in a tertiary hospital during a 5-year period. Cases are gestational trophoblastic neoplasia diagnosed by either rising beta-HCG levels or plateauing beta-HCG levels or by histological evidence of choriocarcinoma. Controls are cases of gestational trophoblastic disease post evacuation with normal HCG regression at 8 weeks. There were 306 controls and 57 cases. RESULTS Tabulated and analysed using SPSS package. Of the 363 patients of gestational trophoblastic disease, 57 (15.7% needed chemotherapy. 98.2% belonged to the age group of 20-35 years. 63% had gestational age of more than 12 weeks, 56.1% had pre-evacuation HCG of more than 40,000. 15.7% needed combination therapy. CONCLUSION 1. 83.1% of patients belonged to age group of 20-30 years. 2. Blood group distribution of patients with gestational trophoblastic disease did not show any significance. 3. 15.7% of total patients were diagnosed to have gestational trophoblastic neoplasia that necessitated chemotherapy. 4. When uterine size was more than 12 weeks, a statistically significant number of patients needed chemotherapy compared to non-chemotherapy group. 5. When BHCG values were more than 40,000, a statistically significant number of patients needed chemotherapy. 6. A risk score of seven or more was found to

  1. The International Permafrost Association: current initiatives for cryospheric research

    Science.gov (United States)

    Schollaen, Karina; Lewkowicz, Antoni G.; Christiansen, Hanne H.; Romanovsky, Vladimir E.; Lantuit, Hugues; Schrott, Lothar; Sergeev, Dimitry; Wei, Ma

    2015-04-01

    The International Permafrost Association (IPA), founded in 1983, has as its objectives to foster the dissemination of knowledge concerning permafrost and to promote cooperation among persons and national or international organizations engaged in scientific investigation and engineering work on permafrost. The IPA's primary responsibilities are convening International Permafrost Conferences, undertaking special projects such as preparing databases, maps, bibliographies, and glossaries, and coordinating international field programs and networks. Membership is through adhering national or multinational organizations or as individuals in countries where no Adhering Body exists. The IPA is governed by its Executive Committee and a Council consisting of representatives from 26 Adhering Bodies having interests in some aspect of theoretical, basic and applied frozen ground research, including permafrost, seasonal frost, artificial freezing and periglacial phenomena. This presentation details the IPA core products, achievements and activities as well as current projects in cryospheric research. One of the most important core products is the circumpolar permafrost map. The IPA also fosters and supports the activities of the Global Terrestrial Network on Permafrost (GTN-P) sponsored by the Global Terrestrial Observing System, GTOS, and the Global Climate Observing System, GCOS, whose long-term goal is to obtain a comprehensive view of the spatial structure, trends, and variability of changes in the active layer thickness and permafrost temperature. A further important initiative of the IPA are the biannually competitively-funded Action Groups which work towards the production of well-defined products over a period of two years. Current IPA Action Groups are working on highly topical and interdisciplinary issues, such as the development of a regional Palaeo-map of Permafrost in Eurasia, the integration of multidisciplinary knowledge about the use of thermokarst and permafrost

  2. Determination of the toughness of a low alloy steel from the Charpy V-notch impact testing

    International Nuclear Information System (INIS)

    Rossoll, A.

    1998-12-01

    Charpy V-notch (CVN) impact testing is widely used to characterize the resistance of a material to brittle fracture, by measuring the energy consumed by a specimen during impact. Notably materials undergoing a ductile-to-brittle transition, e.g. ferritic steels, are quality controlled by means of CVN testing, and their ductile-to-brittle transition temperature can be determined. Charpy testing is also widely used in the toughness assessment of large forged components, e.g. pressure vessels for pressurised water reactors (PWR). However, currently no satisfactory link between the Charpy impact energy CVN and the fracture toughness KIc exists. This study aims to establish a non-empirical relationship between the Charpy V-notch energy CVN, and the fracture toughness KIc, on the lower shelf of fracture toughness and the onset of the ductile-to-brittle transition of a A508 Cl.3 steel. The methodology employed is based on the so-called 'local approach'. Brittle cleavage fracture is modelled in terms of the Beremin (1983) model based on 'weakest link' statistics, whereas ductile crack advance preceding cleavage in the transition region is accounted for with the GTN model (Gurson, 1977; Tvergaard, 1982; Tvergaard and Needleman, 1984). Mechanical testing at different strain rates allowed for the establishment of the constitutive equations of the material in an elastic-viscoplastic formulation. Fracture tests on different specimen geometries provided the large data set necessary for statistical evaluation. All specimen types have been modelled with finite element analysis. However, the dynamic nature of the Charpy test requires special consideration. The origin of these dynamic effects was studied, as well as their implications on interpretation of experimental results and on modeling. After a proper modeling procedure had been defined, the local approach was employed for studying fracture. It is found that the fracture toughness can be predicted from the Charpy impact test

  3. Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

    Science.gov (United States)

    Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

    2003-07-01

    The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of

  4. Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Rajinikanth PS

    2016-10-01

    Full Text Available Paruvathanahalli Siddalingam Rajinikanth,1,2 Jestin Chellian2 1School of Pharmacy, Taylors University, 2School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia Abstract: The aim of this study was to develop a nanostructured lipid carrier (NLC-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU. Precirol® ATO 5 (glyceryl palmitostearate and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid] gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 µg/cm2/h as compared with plain 5-FU gel (2.85±1.12 µg/cm2/h. Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 µg/cm2 as compared with that from the 5-FU plain gel (12.23±3.86 µg/cm2 in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations. Keywords: nanostructured lipid carrier, topical delivery, controlled release, 5-fluorouracil, skin penetration, skin infection

  5. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    Directory of Open Access Journals (Sweden)

    Maheshkumar P Soni

    2014-01-01

    Full Text Available Background: Buparvaquone (BPQ, a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES organs. The present study investigates development of solid lipid nanoparticles (SLN of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C. Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC, powder X-ray diffraction (XRD and scanning electron microscope (SEM study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8% and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52% uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed

  6. Method developments approaches in supercritical fluid chromatography applied to the analysis of cosmetics.

    Science.gov (United States)

    Lesellier, E; Mith, D; Dubrulle, I

    2015-12-04

    Analyses of complex samples of cosmetics, such as creams or lotions, are generally achieved by HPLC. These analyses are often multistep gradients, due to the presence of compounds with a large range of polarity. For instance, the bioactive compounds may be polar, while the matrix contains lipid components that are rather non-polar, thus cosmetic formulations are usually oil-water emulsions. Supercritical fluid chromatography (SFC) uses mobile phases composed of carbon dioxide and organic co-solvents, allowing for good solubility of both the active compounds and the matrix excipients. Moreover, the classical and well-known properties of these mobile phases yield fast analyses and ensure rapid method development. However, due to the large number of stationary phases available for SFC and to the varied additional parameters acting both on retention and separation factors (co-solvent nature and percentage, temperature, backpressure, flow rate, column dimensions and particle size), a simplified approach can be followed to ensure a fast method development. First, suited stationary phases should be carefully selected for an initial screening, and then the other operating parameters can be limited to the co-solvent nature and percentage, maintaining the oven temperature and back-pressure constant. To describe simple method development guidelines in SFC, three sample applications are discussed in this paper: UV-filters (sunscreens) in sunscreen cream, glyceryl caprylate in eye liner and caffeine in eye serum. Firstly, five stationary phases (ACQUITY UPC(2)) are screened with isocratic elution conditions (10% methanol in carbon dioxide). Complementary of the stationary phases is assessed based on our spider diagram classification which compares a large number of stationary phases based on five molecular interactions. Secondly, the one or two best stationary phases are retained for further optimization of mobile phase composition, with isocratic elution conditions or, when

  7. Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Cristiane de Oliveira

    Full Text Available Studying the uptake of 2-deoxy glucose (2-DG analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor during mild and severe biliary AP.Wistar rats (300 g; 8-12/group were administered NIR 2-DG (10 nM; I.V.. Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g within 10 minutes of giving NIR 2-DG. Controls (CON only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP.NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality

  8. A novel method to produce solid lipid nanoparticles using n-butanol as an additional co-surfactant according to the o/w microemulsion quenching technique.

    Science.gov (United States)

    Mojahedian, Mohammad M; Daneshamouz, Saeid; Samani, Soliman Mohammadi; Zargaran, Arman

    2013-09-01

    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are novel medicinal carriers for controlled drug release and drug targeting in different roots of administration such as parenteral, oral, ophthalmic and topical. These carriers have some benefits such as increased drug stability, high drug payload, the incorporation of lipophilic and hydrophilic drugs, and no biotoxicity. Therefore, due to the cost-efficient, proportionally increasable, and reproducible preparation of SLN/NLC and the avoidance of organic solvents used, the warm microemulsion quenching method was selected from among several preparation methods for development in this research. To prepare the warm O/W microemulsion, lipids (distearin, stearic acid, beeswax, triolein alone or in combination with others) were melted at a temperature of 65°C. After that, different ratios of Tween60 (10-22.5%) and glyceryl monostearate (surfactant and co-surfactant) and water were added, and the combination was stirred. Then, 1-butanol (co-surfactant) was added dropwise until a clear microemulsion was formed and titration continued to achieve cloudiness (to obtain the microemulsion zone). The warm o/w microemulsions were added dropwise into 4°C water (1:5 volume ratio) while being stirred at 400 or 600 rpm. Lipid nanosuspensions were created upon the addition of the warm o/w microemulsion to the cold water. The SLN were obtained over a range of concentrations of co-surfactants and lipids and observed for microemulsion stability (clearness). For selected preparations, characterization involved also determination of mean particle size, polydispersity and shape. According to the aim of this study, the optimum formulations requiring the minimum amounts of 1-butanol (1.2%) and lower temperatures for creation were selected. Mono-disperse lipid nanoparticles were prepared in the size range 77 ± 1 nm to 124 ± 21 nm according to a laser diffraction particle size analyzer and transmission electron

  9. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  10. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range; Modelisation de l'essai Charpy par l'approche locale de la rupture. Application au cas de l'acier 16MND5 dans le domaine de transition

    Energy Technology Data Exchange (ETDEWEB)

    Tanguy, B

    2001-07-15

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  11. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range

    International Nuclear Information System (INIS)

    Tanguy, B.

    2001-07-01

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  12. Permafrost: An International Approach to 21th Century Challenges

    Science.gov (United States)

    Brown, J.

    2003-12-01

    Whereas glaciers are easily discernible to the human eye and satellites, permafrost terrains and their physical components are not easily detected from the surface without supplemental knowledge and measurements. In the Northern Hemisphere, approximately 17 million km2 of exposed land contains some extent of permafrost or ground that remains frozen for more than two years. The vast majority, or 11 million km2, of permafrost terrain has temperatures of 5° C or below, with perennially frozen ground underlying essentially all ground surfaces to considerable depths. Permafrost in the remaining regions, including mid-latitude mountains, is both warmer and is spatially variable (discontinuous). As climate warms the uppermost permafrost is subjected to increase thaw with resulting ground subsidence, accelerated erosion, and related biogeochemical modifications. The challenging questions to geocryologists, modelers and the public relate to the rate of change and the spatial variability of the projected thaw, particularly in the warmer zones where actual areal and subareal distribution of permafrost is poorly known. An international network of active layer measurements and borehole sites now exists under the Global Climate Observing System (GCOS), but requires additional sites for representative coverage. This Global Terrestrial Network for Permafrost (GTN-P) is coordinated by the 24-member, International Permafrost Association. At the Eighth International Conference on Permafrost (ICOP) in Zurich in July 2003, the IPA Council agreed on the scope of new activities for the next five years, many of which will be undertaken in cooperation with other international organizations (e.g. WCRP/CliC; ICSI, IASC, SCAR, IGU, IUGS). Examples of the activities of the IPA Working Groups are: 1. Antarctic Permafrost and Periglacial Environments (active layer processes, maps, database). 2. Coastal and Offshore Permafrost (sediment and organic transfers, subsea permafrost dynamics). 3

  13. Numerical modelling of Charpy-V notch test by local approach to fracture. Application to an A508 steel in the ductile-brittle transition range; Modelisation de l'essai Charpy par l'approche locale de la rupture. Application au cas de l'acier 16MND5 dans le domaine de transition

    Energy Technology Data Exchange (ETDEWEB)

    Tanguy, B

    2001-07-15

    Ferritic steels present a transition of the rupture mode which goes progressively of a brittle rupture (cleavage) to a ductile rupture when the temperature increases. The following of the difference of the transition temperature of the PWR vessel steel by the establishment of toughness curves makes of the Charpy test an integrating part of the monitoring of the French PWR reactors. In spite of the advantages which are adapted to it in particular its cost, the Charpy test does not allow to obtain directly a variable which characterizes a crack propagation resistance as for instance the toughness used for qualifying the mechanical integrity of a structure. This work deals with the establishment of the through impact strength-toughness in the transition range of the vessel steel: 16MND5 from a non-empirical approach based on the local approach of the rupture. The brittle rupture is described by the Beremin model (1983), which allows to describe the dispersion inherent in this rupture mode. The description of the brittle fissure is carried out by the GTN model (1984) and by the Rousselier model (1986). This last model has been modified in order to obtain a realistic description of the brittle damage in the case of fast solicitations and of local heating. The method proposed to determine the parameters of the damage models depends only of tests on notched specimens and of the inclusion data of the material. The behaviour is described by an original formulation parametrized in temperature which allows to describe all the tests carried out in this study. Before using this methodology, an experimental study of the behaviour and of the rupture modes of the steel 16MND5 has been carried out. From the toughness tests carried out in quasi-static and dynamical conditions, it has been revealed that this steel does not present important unwedging of its toughness curve due to the velocity effect. In the transition range, local heating of about 150 C have been measured in the root

  14. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-10-01

    Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens (ether glycerophosphoethanolamine lipids are decreased in these genetic disorders. The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid (PPI-1011 to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 (RCDP1 and rhizomelic chrondrodysplasia punctata type 2 (RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis. We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease (PMD lymphocytes which possess a proteolipid protein-1 (PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum (ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency. Results In both RCDP1 and RCDP2 lymphocytes, PPI-1011 repleted the target ethanolamine plasmalogen (PlsEtn16:0/22:6 in a concentration dependent manner. In addition, deacylation/reacylation reactions resulted in repletion of PlsEtn 16:0/20:4 in both RCDP1 and RCDP2 lymphocytes, repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP2 lymphocytes, and partial repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP1 lymphocytes. In the Pex7 mouse, oral dosing of labeled PPI-1011 demonstrated repletion of tissue levels of the target plasmalogen PlsEtn 16:0/22:6 with phospholipid remodeling also resulting in significant repletion of PlsEtn 16:0/20:4 and PlsEtn 16:0/18:1. Metabolic conversion of PPI-1011 to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI-1011 is activated

  15. A national strategy for a long-term monitoring of permafrost and periglacial processes and their relationship to natural hazard prevention in Austria

    Science.gov (United States)

    Kellerer-Pirklbauer, Andreas; Bartsch, Annett; Gitschthaler, Christoph; Reisenhofer, Stefan; Weyss, Gernot; Riedl, Claudia; Avian, Michael

    2016-04-01

    About 2.5% (~2000 km²) of the national territory of Austria is influenced by permafrost conditions. A slightly smaller area of Austria is additionally affected by deep seasonal frost which is, however, similarly exposed to intensive physical weathering and related geomorphic processes. Currently, 23 skiing resorts, 31 water reservoirs and 42 mountain huts are either directly or indirectly influenced by permafrost and associated processes in Austria as determined from regional permafrost models. Ground thermal changes most likely affect the ground stability and infrastructure in those areas. Therefore, changes in the distribution and characteristics of permafrost and seasonal frost are of high economic and ecological importance. A range of Austrian institutions are interested in systematic permafrost monitoring (several universities, geological surveys, the Austrian torrent and avalanche control agency or several different alpine clubs). However, to date no coordinated monitoring network has been established on a national scale and a strategy for long-term permafrost/periglacial observation did not exist so far. Such a national strategy has been developed in 2015 within the permAT project funded through the StartClim2014-program. During permAT an extensive literature review and data search as well as a workshop with 40 participants (scientists, stakeholder and policy maker) were accomplished. The workshop allowed the integration of national as well as international colleagues into the strategy development. Results of permAT clearly demonstrate that the number of present permafrost/periglacial monitoring sites is far too little in Austria. Only few alpine areas of Austria are well represented by the existing monitoring activities but large areas lack such instrumentations. Furthermore, permafrost boreholes exist at only three sites in central Austria (all contribution to the GTN-P network) and there is a lack of knowledge about thermal conditions and recent changes

  16. Preparation, characterization and evaluation of moisturizing and UV protecting effects of topical solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Shiva Golmohammadzadeh

    2012-12-01

    Full Text Available Solid lipid nanoparticles (SLN were recently proposed as carriers for various pharmaceutical and cosmetic actives. These lipid nanoparticles can act as moisturizers and physical sunscreens on their own. Therefore, the full potential of these carriers has yet to be determined. The present study was aimed to determine and compare moisturizing and UV-protecting effects of different solid lipid nanoparticles (SLN prepared by different solid lipids including Glyceryl monostearate (GMS, Precirol® (P and cetyl palmitate (CP as carrier systems of moisturizers and sunscreens. The influence of the size and matrix crystallinity of the solid lipids on the occlusive factor, skin hydration and UV-protection were evaluated by in vitro and in vivo methods. The SLN were prepared by high-shear homogenization and ultrasound methods. Size, zeta potential and morphological characteristics of the samples were assessed by transmission electron microscopy (TEM and thermotropic properties with differential scanning calorimetry (DSC technique. Results of the assessments showed that SLN-CP significantly increases skin hydration and UV-protection, compared to SLN-GMS and SLN-P. It was demonstrated that the size of SLN, crystallinity index of solid lipid in SLN and probably other mechanisms besides the occlusive factor can influence skin hydration and UV-protection indices. Furthermore, findings of the assessments demonstrated significant difference between in vitro and in vivo assessments regarding occlusive factor and moisturizing effects. Findings of the present study indicate that the SLN-CP could be a promising carrier for sunscreens and moisturizers.Nanopartículas lipídicas sólidas (NLS foram, recentemente, propostas como carreadores de vários ativos cosméticos e farmacêuticos. Essas nanopartículas lipídicas podem atuar como hidratantes e protetores solares físicos por si só. Assim sendo, determinou-se o potencial desses carreadores. Os objetivos do

  17. NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1993-08-01

    increased incidences of squamous cell carcinomas of the oral mucosa, squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, harderian gland adenomas, and uterine adenomas, adenocarcinomas, and stromal polyps. Nonneoplastic lesions associated with exposure to 1,2,3-trichloropropane included increased severity of nephropathy in male rats and increased incidences of basal cell and squamous hyperplasia of the forestomach, acinar hyperplasia of the pancreas, renal tubule hyperplasia, and preputial or clitoral gland hyperplasia in male and female rats. Increased incidences of squamous hyperplasia of the forestomach and eosinophilic foci in the liver in male and female mice were chemical related. Synonyms: Allyl trichloride, glycerol tnchlorohydrin, glyceryl tnchlorohydrin, trichlorohydrin