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Sample records for orally-administered glycyrrhizic acid-treated

  1. Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats

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    Ton So

    2009-07-01

    Full Text Available Abstract Background The metabolic syndrome (MetS is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR. With the onset of IR, the expression of lipoprotein lipase (LPL, a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA, the bioactive constituent of licorice roots (Glycyrrhiza glabra inhibits 11β-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS. Results In this study, daily oral administration of 50 mg/kg of GA for one week led to significant increase in LPL expression in the quadriceps femoris (p p > 0.05 of the GA-treated rats compared to the control. Decrease in adipocyte size (p > 0.05 in both the visceral and subcutaneous adipose tissue depots accompanies such selective induction of LPL expression. Consistent improvement in serum lipid parameters was also observed, with decrease in serum free fatty acid, triacylglycerol, total cholesterol and LDL-cholesterol but elevated HDL-cholesterol (p > 0.05. Histological analysis using tissue lipid staining with Oil Red O showed significant decrease in lipid deposition in the abdominal muscle and quadriceps femoris (p p > 0.05. Conclusion Results from this study may imply that GA could counteract the development of visceral obesity and improve dyslipidaemia via selective induction of tissue LPL expression and a positive shift in serum lipid parameters respectively, and retard the development of IR associated with tissue steatosis.

  2. Urinary metabolites of daidzin orally administered in rats.

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    Yasuda, T; Ohsawa, K

    1998-09-01

    In a study on the metabolism of flavonoids, the isoflavone glycoside daidzin was orally administered to rats. Urine samples were collected and treated with beta-glucuronidase and arylsulfatase. Aglycone daidzein (M3) and other three metabolites, 3',4',7-trihydroxyisoflavone (M1), 4',7-dihydroxyisoflavanone (M2) and 4',7-dihydroxyisoflavan (M4) were isolated from the urine following treatment with enzymes. The structures of M1, M2 and M4 were determined on the basis of chemical and spectral data.

  3. Human metabolism of orally administered radioactive cobalt chloride.

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    Holstein, H; Ranebo, Y; Rääf, C L

    2015-05-01

    This study investigated the human gastrointestinal uptake (f1) and subsequent whole-body retention of orally administered inorganic radioactive cobalt. Of eight adult volunteers aged between 24 and 68 years, seven were given solutions of (57)Co (T1/2 = 272 d) containing a stable cobalt carrier, and six were given carrier-free (58)Co (T1/2 = 71 d). The administered activities ranged between 25 and 103 kBq. The observed mean f1, based on 6 days accumulated urinary excretion sampling and whole-body counting, was 0.028 ± 0.0048 for carrier-free (58)Co, and 0.016 ± 0.0021 for carrier-associated (57)Co. These values were in reasonable agreement with values reported from previous studies involving a single intake of inorganic cobalt. The time pattern of the total retention (including residual cobalt in the GI tract) included a short-term component with a biological half-time of 0.71 ± 0.03 d (average ± 1 standard error of the mean for the two nuclides), an intermediate component with a mean half-time of 32 ± 8.5 d, and a long-term component (observed in two volunteers) with half-times ranging from 80 to 720 d for the two isotopes. From the present data we conclude that for the short-lived (57)Co and (58)Co, more than 95% of the internal absorbed dose was delivered within 7 days following oral intake, with a high individual variation influenced by the transit time of the unabsorbed cobalt through the gastro-intestinal tract. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    2007-01-01

    Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of

  5. Effects of orally administered bovine lactoperoxidase on dextran sulfate sodium-induced colitis in mice.

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    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Takase, Mitsunori; Yaeshima, Tomoko; Iwatsuki, Keiji

    2008-07-01

    The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.

  6. Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.

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    Lin Fu

    Full Text Available Lipopolysaccharide (LPS has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR, neural tube defects (NTDs and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg daily from gestational day (GD8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.

  7. Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

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    Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

    2014-07-01

    Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

  8. Orally administered misoprostol for induction of labor with prelabor rupture of membranes at term.

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    Radoff, Kari A

    2014-01-01

    Prelabor rupture of membranes (PROM) occurs in approximately 8% to 10% of women with term pregnancies. The management of PROM continues to be controversial. Approaches include expectant management and immediate induction of labor. The use of orally administered misoprostol for the management of women with PROM may provide significant advantages when they choose immediate induction of labor. This literature review presents current evidence that supports the use of oral misoprostol for women with PROM, including the benefits of a decreased interval time from PROM to vaginal birth, good safety profile, and reductions in the use of oxytocin augmentation and epidural anesthesia. In addition to clinically proven benefits to women of oral misoprostol for PROM, it also has the potential to reduce chorioamnionitis by reducing the number of sterile vaginal examinations performed thereby reducing the risk of ascending bacteria. Women have also reported acceptability and satisfaction when using oral misoprostol for immediate induction of labor. This review of literature discusses what is known about the use of orally administered misoprostol for the management of term PROM and makes recommendations for clinical use.

  9. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

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    John K. Triantafillidis

    2014-01-01

    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  10. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

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    Lee JA

    2014-12-01

    Full Text Available Jeong-A Lee,1 Mi-Kyung Kim,1 Hee-Jeong Paek,1 Yu-Ri Kim,2 Meyoung-Kon Kim,2 Jong-Kwon Lee,3 Jayoung Jeong,3 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Republic of Korea; 3Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk–do, Republic of Korea Purpose: The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods: Silica nanoparticles of two different sizes (20 nm and 100 nm were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results: The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion: The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ

  11. Curative and preventive efficacy of orally administered afoxolaner against Ctenocephalides canis infestation in dogs.

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    Dumont, Pascal; Gale, Boyd; Chester, Theodore S; Larsen, Diane L

    2014-04-02

    The efficacy of orally administered afoxolaner against adult dog fleas, Ctenocephalides canis, was evaluated in a controlled, blinded study. A total of 32 dogs were infested with 100 adult unfed fleas approximately 24h prior to treatment and then at weekly intervals for 5 weeks after treatment. Live fleas were counted upon removal at 12h (for 16 dogs) and 24h (for the remaining 16 dogs) after treatment (for counts performed the first week) or after infestation (for counts performed on subsequent weeks). In addition, flea eggs were collected from each pen and counted for the dogs with flea removal at 24h. Dosing of individual dogs was achieved using a combination of the chewable tablets to be as close as possible to the minimum effective dose of 2.5mg/kg. The percent efficacy of the afoxolaner treatment was ≥ 99.0% for all 24-h flea counts. For flea counts performed 12h after treatment or infestations, the percent efficacy was ≥ 94.1% up to Day 21. After Day 1, no flea eggs were recovered from the afoxolaner treated group, providing 100% reduction in numbers of flea eggs recovered versus untreated control group. This study confirmed that a single oral treatment with afoxolaner provided excellent efficacy against infestations by C. canis within 12-24h after treatment, prevented re-infestations, and completely prevented egg production from new flea infestations for up to 5 weeks.

  12. Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

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    Pennapa Chonpathompikunlert

    Full Text Available Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8 mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood. After treatment for one month, levels of oxidative stress in the brain of SAMP8 mice were remarkably reduced by treatment with redox nanoparticles, compared to that observed with low-molecular-weight nitroxide radicals, resulting in the amelioration of cognitive impairment with increased numbers of surviving neurons. Additionally, treatment by redox nanoparticles did not show any detectable toxicity. These findings indicate the potential of redox polymer nanotherapeutics for treatment of the neurodegenerative diseases.

  13. Gene delivery to dendritic cells by orally administered recombinant Saccharomyces cerevisiae in mice.

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    Kiflmariam, Meron G; Yang, Hanjiang; Zhang, Zhiying

    2013-02-27

    DNA vaccination has caught the attention of many for triggering humoral as well as cellular immune responses. And delivering DNA into the antigen presenting cells (APCs) in order to induce efficient immunoresponse has become the backbone of this field. It has been confirmed that Saccharomyces cerevisiae, though non-pathogenic, is being engulfed by the dendritic cells and macrophages and delivers not only proteins, but also DNA materials (already confirmed in vitro). In this research, S. cerevisiae is used to deliver green fluorescent protein (GFP) reporter gene controlled under cytomegalovirus (CMV) promoter in living organism (mice). The recombinant yeast, transfected with the plasmid containing the GFP gene, was heat killed and orally administered to mice. After 60 h of yeast administration, mice were sacrificed and intestine was separated, washed and frozen in liquid nitrogen. Tissues were cut at the size of 10 μm using Cryostat machine, and GFP expression was successfully detected under a fluorescence microscope. After 45 days Western blot was able to detect GFP antibody in the blood of mice. These results imply that S. cerevisiae, being non-pathogenic, cheap, and easy to culture could be a good candidate to deliver DNA materials to the immune cells for vaccination.

  14. Evaluation of ATC as an Orally Administered Drug in Treatment of Cadmium Toxicity of Rat Organs

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    S. Nabilaldine Fatemi

    2009-01-01

    Full Text Available The effect of N-tetramethylene dithiocarbamate (ATC as a chelating agent on the excretion of cadmium was evaluated in cadmium-poisoned Wistar rats following administration through food and drink. The present research aimed to characterize the potential efficiency of ATC as an orally administered chelator drug after cadmium administration for 60 days. This chelator significantly enhanced the urinary and biliary excretion of cadmium and restored the altered levels of iron. Cadmium and iron concentrations in different tissues were determined by graphite furnace and flame atomic absorption spectrometry (GF AAS and F AAS methods, respectively. The chelation therapy results show that ATC is able to remove cadmium ions from different tissues while iron concentration returned to the normal level and the clinical symptoms were also reduced. In summary, we conclude that ATC is able to mobilize and promote the excretion of cadmium in rat organs and reduce the side effects and general symptoms of toxicity caused by cadmium and might be useful for preliminary testing of the efficacy of chelating agents in human body. However, these results should be confirmed in different experimental models before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in cadmium toxicity.

  15. Orally administered DTPA penta-ethyl ester for the decorporation of inhaled (241)Am.

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    Sueda, Katsuhiko; Sadgrove, Matthew P; Huckle, James E; Leed, Marina G D; Weber, Waylon M; Doyle-Eisele, Melanie; Guilmette, Raymond A; Jay, Michael

    2014-05-01

    Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [(14) C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared with a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of (241) Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of (241) Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Orally administered DTPA penta-ethyl ester for the decorporation of inhaled 241Am

    Science.gov (United States)

    Sueda, Katsuhiko; Sadgrove, Matthew P.; Huckle, James E.; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Jay, Michael

    2014-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [14C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared to a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of 241Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of 241Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. PMID:24619514

  17. Urinary excretion of orally administered oxalic acid in saccharin and o-phenylphenol-fed NMRI mice.

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    Salminen, E; Salminen, S

    1986-01-01

    Both saccharin and o-phenylphenol have been suggested to be carcinogenic to the urinary bladder in experimental animals, but the mechanism has remained unclear. The aim of this study was to investigate the effects of dietary saccharin and o-phenylphenol on the urinary excretion of dietary oxalic acid. Male NMRI mice were gradually adapted to either 3% o-phenylphenol or 5% saccharin in their diet. Having being adapted to these diets for 1 week or after consuming them for 3 months, the animals were fasted for 6 h and given a 2.5-microCi oral dose of U-14C-oxalic acid. Dosed animals were kept in metabolism cages for 48 h to monitor urinary and fecal excretion of the label. Adaptation to dietary o-phenylphenol appeared to increase the urinary excretion of orally administered U-14C-oxalic acid when food and water were available during urinary and fecal collections. Adaptation to dietary saccharin had little effect on urinary oxalate levels when compared to control animals. These results indicate that changes in urinary oxalate levels should be more carefully studied in connection with potential urinary bladder carcinogens to avoid the possibility of bladder irritation by increased urinary oxalate excretion.

  18. Effect of Orally Administered Glutathione-Montmorillonite Hybrid Systems on Tissue Distribution

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    Miri Baek

    2012-01-01

    Full Text Available An ubiquitous tripeptide, glutathione (GSH, is assigned a role in detoxification, activation of immune system, intermediary metabolism, transport, and protection of cells against free radicals or reactive oxygen species. However, instability of orally administered GSH in gastrointestinal (GI tract leads to low absorption and low bioavailability in tissues. In this study, we attempted to synthesize GSH-montmorillonite (MMT hybrid systems by intercalating GSH into the interlayers of a cationic clay delivery carrier, MMT, to improve GSH bioavailability at the systemic level. Polymer coating of the hybrid with polyvinylacetal diethylaminoacetate (AEA was further performed to obtain better stability. Synthetic condition of both GSH-MMT and AEA-GSH-MMT hybrids was optimized, and then GSH-delivery efficiency was evaluated in various organs after oral administration in normal as well as GSH-deficient mice. The present GSH-MMT hybrids remarkably enhanced GSH concentration in the plasma, heart, kidney, and liver, especially when AEA-GSH-MMT hybrid was administered under GSH-deficient condition. Moreover, both hybrids did not induce acute oral toxicity up to 2000 mg/kg, suggesting their great potential for pharmaceutical application.

  19. Effects of orally administered yeast-derived beta-glucans: a review.

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    Samuelsen, Anne Berit C; Schrezenmeir, Jürgen; Knutsen, Svein H

    2014-01-01

    Yeast-derived beta-glucans (Y-BG) are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. Specific preparations have received Generally Recognized as Safe status and acceptance as novel food ingredients by European Food Safety Authority. In human trials, orally administered Y-BG significantly reduced the incidence of upper respiratory tract infections in individuals susceptible to upper respiratory tract infections, whereas significant differences were not seen in healthy individuals. Increased salivary IgA in healthy individuals, increased IL-10 levels in obese subjects, beneficial changes in immunological parameters in allergic patients, and activated monocytes in cancer patients have been reported following Y-BG intake. The studies were conducted with different doses (7.5-1500 mg/day), using different preparations that vary in their primary structure, molecular weight, and solubility. In animal models, oral Y-BG have reduced the incidence of bacterial infections and levels of stress-induced cytokines and enhanced antineoplastic effects of cytotoxic agents. Protective effects toward drug intoxication and ischemia/reperfusion injury have also been reported. In conclusion, additional studies following good clinical practice principles are needed in which well-defined Y-BG preparations are used and immune markers and disease endpoints are assessed. Since optimal dosing may depend on preparation characteristics, dose-response curves might be assessed to find the optimal dose for a specific preparation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Tolerability assessment of a lectin fraction from Tepary bean seeds (Phaseolus acutifolius orally administered to rats

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    Roberto Ferriz-Martínez

    2015-01-01

    Full Text Available Our previous studies have shown that a lectin rich fraction (TBLF extracted from Tepary bean seeds differentially inhibits cancer cells proliferation in vitro. Before testing the in vivo anticancer effect, the acute and subchronic toxicological assays in rats were conducted, where an oral dose of 50 mg/body weight kg was determined as the NOAEL. This study evaluated the resistance to digestion and complete blood count (CBC after 24 h of the orally administered 50 mg/kg TBLF. The digestion resistance test showed lectins activity retention after 72 h and the CBC study showed a high level of eosinophils, suggesting an allergic-like response. Tolerability was assayed after 6 weeks of treatment by dosing with an intragastric cannula every third day per week. It was observed a transient reduction in food intake and body weight in the first weeks, resulting in body weight gain reduction of 10% respect to the control group at the end of the study. Additionally, organs weight, histopathological analysis and blood markers for nutritional status and for liver, pancreas and renal function were not affected. Our results suggest that 50 mg/kg TBLF administered by oral route, exhibit no toxicity in rats and it was well tolerated. Further studies will focus on long-term studies.

  1. Identification and quantification of metabolites of orally administered naringenin chalcone in rats.

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    Yoshimura, Mineka; Sano, Atsushi; Kamei, Jun-Ichi; Obata, Akio

    2009-07-22

    Naringenin chalcone is the main active component of tomato skin extract, which has an antiallergic activity. In this study, naringenin chalcone was orally administered to rats, and the chemical structures and levels of the major metabolites in the plasma and urine of rats were determined. HPLC analysis indicated the presence of three major metabolites in the urine. LC-MS and NMR analyses tentatively identified these as naringenin chalcone-2'-O-beta-D-glucuronide, naringenin-7-O-beta-D-glucuronide, and naringenin-4'-O-beta-D-glucuronide. Naringenin chalcone-2'-O-beta-D-glucuronide was the only metabolite detected in the plasma, and its peak plasma level was observed 1 h after naringenin chalcone administration. Naringenin chalcone-2'-O-beta-D-glucuronide also inhibited histamine release from rat peritoneal mast cells stimulated with compound 48/80. This activity might contribute to the antiallergic activity of naringenin chalcone in vivo. To the best of the authors' knowledge, this study is the first to report determination of naringenin chalcone metabolites in rat plasma and urine.

  2. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

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    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  3. Orally administered tylosin for the control of pneumonia in neonatal calves.

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    Matsuoka, T; Muenster, O A; Ose, E E; Tonkinson, L

    1980-08-16

    The effectiveness of orally administered tylosin tartrate for the control of naturally occurring pneumonia was determined in 287 neonatal calves. Tylosin tartrate was mixed with reconstituted milk replacer at the time of feeding. Daily doses of 1.0 g (0.5 g BID), 2.0 g (1.0 g BID) and 4.0 g (2.0 g BID) were evaluated for periods ranging from seven to 28 days. Tylosin at the optimum dose of 2.0 g daily reduced mortality to 12 out of 95 (12.6 per cent) compared to 38 out of 89 (42.7 per cent) in the non-medicated control calves. The 1.0 g daily dose did not reduce mortality. The number of calves with moderate to severe lung lesions was also reduced by treatment at 2.0 g daily to 13 out of 95 (13.7 per cent) compared to 45 out of 89 (50.6 per cent) in the control group. All dose levels had a similar effect in reducing the severity of clinical signs indicative of respiratory disease. Tylosin treatment at all dose levels reduced the number of Pasteurella multocida isolations from lung tissue to 15/146 (10.3 per cent) compared to 61/141 (43.3 per cent) for the controls. However, there were no differences between treated and controls in the number of P haemolytica isolations. The frequency of mycoplasma isolations from lung tissue were reduced significantly by tylosin treatment at the 4.0 g and 2.0 g dose levels to 36/93 (38.7 per cent) compared to 61/86 (70.9 per cent) for the control calves.

  4. Application of the yeast-surface-display system for orally administered salmon calcitonin and safety assessment.

    Science.gov (United States)

    Sun, Ping-Nan; Zhang, Xue-Cheng; Chen, Yun-Song; Zang, Xiao-Nan

    2010-01-01

    High manufacturing costs and oral delivery are the constraints in clinical application of calcitonin. We selected surface-displayed Saccharomyces cerevisiae as a low-cost and safe carrier for oral delivery of salmon calcitonin (sCT). The sCT DNA fragment, optimized according to the codon preference of S. cerevisiae, was synthesized and cloned into the plasmid M-pYD1 to yield recombinant yAGA2-sCT, which was induced to express sCT by galactose for 0, 12, and 24 h. sCT expression was detected on the cell surface by indirect immunofluorescence and peaked at 12 h. About 65% recombinants expressed sCT on flow cytometry. The in vivo and in vitro activity of recombinant sCT was determined by detecting bioactivity of antiosteoclastic absorption on bone wafers and orally administering yAGA2-sCT to Wistar rats, respectively. For safety assessment of yAGA2-sCT, we observed abnormalities, morbidity, and mortality and determined body weight, serum chemistry parameters, hematological parameters, and organ weight. In vitro bioactivity of the recombinant sCT was similar to that of commercial sCT, Miacalcic; oral administration of 5 g/kg yAGA2-sCT induced a long-term hypocalcemic effect in Wistar rats and no adverse effects. This study demonstrates that yAGA2-sCT anchoring sCT protein on a S. cerevisiae surface has potential for low-cost and safe oral delivery of sCT.

  5. Orally administered bisphenol a in rainbow trout (Oncorhynchus mykiss): estrogenicity, metabolism, and retention.

    Science.gov (United States)

    Bjerregaard, Poul; Andersen, Sidsel B; Pedersen, Knud L; Pedersen, Søren N; Korsgaard, Bodil

    2007-09-01

    The estrogenic effect of orally administered bisphenol A (BPA) was investigated in a rainbow trout (Oncorhynchus mykiss) test system. Bisphenol A was administered orally to sexually immature rainbow trout every second day for up to 12 d in doses between 1.8 and 258 mg/kg every second day (/2d). Plasma vitellogenin was measured before and during the exposures, and the concentrations of BPA in plasma, liver, and muscle and the plasma concentrations of BPA glucuronic acid (BPAGA) were determined at the end of the experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 24 mg BPA/kg/2d; the most sensitive fish responded to 9.3 mg/kg/2d. At day 12, the 10, 50, and 90% effective doses for increase in vitellogenin synthesis were 13, 19, and 25 mg/kg/2d, respectively. Bisphenol A could be detected in liver, muscle, and plasma at the end of the exposure, generally in increasing concentrations with increasing doses; liver concentrations generally were higher than muscle concentrations. Four to five hours after the last feeding of doses between 3.6 and 24 mg BPA/kg, plasma BPA concentrations ranged between 400 and 1,200 nM, whereas BPAGA concentrations were between 2- and 10-fold higher. The difference between BPA and BPAGA concentrations increased with increasing BPA dose. Bisphenol A showed little tendency to bioaccumulate in rainbow trout; less than 1% of the total amount of BPA administered orally at doses between 1.8 and 258 mg/ kg/2d over the 10- or 12-d experimental period was retained in muscle and liver at 5 or 24 h after the end of the experiments.

  6. Effectiveness and safety of orally administered immunotherapy for food allergies: a systematic review and meta-analysis.

    Science.gov (United States)

    Nurmatov, Ulugbek; Devereux, Graham; Worth, Allison; Healy, Laura; Sheikh, Aziz

    2014-01-14

    The aim of using oral and sublingual immunotherapy with food allergies is to enable the safe consumption of foods containing these allergens in patients with food allergies. In the present study, a systematic review of intervention studies was undertaken; this involved the searching of eleven international databases for controlled clinical trials. We identified 1152 potentially relevant papers, from which we selected twenty-two reports of twenty-one eligible trials (i.e. eighteen randomised controlled trials and three controlled clinical trials). The meta-analysis revealed a substantially lower risk of reactions to the relevant food allergen in those receiving orally administered immunotherapy (risk ratios (RR) 0·21, 95 % CI 0·12, 0·38). The meta-analysis of immunological data demonstrated that skin prick test responses to the relevant food allergen significantly decreased with immunotherapy (mean difference - 2·96 mm, 95 % CI - 4·48, - 1·45), while allergen-specific IgG4 levels increased by an average of 19·9 (95 % CI 17·1, 22·6) μg/ml. Sensitivity analyses excluding studies at the highest risk of bias and subgroup analyses in relation to specific food allergens and treatment approaches generated comparable summary estimates of effectiveness and immunological changes. Pooling of the safety data revealed an increased risk of local (i.e. minor oropharyngeal/gastrointestinal) adverse reactions with immunotherapy (RR 1·47, 95 % CI 1·11, 1·95); there was a non-significant increased average risk of systemic adverse reactions with immunotherapy (RR 1·08, 95 % CI 0·97, 1·19). There is strong evidence that orally administered immunotherapy can induce immunomodulatory changes and thereby promote desensitisation to a range of foods. However, given the paucity of evidence on longer-term safety, effectiveness and cost-effectiveness, orally administered immunotherapy should not be used outside experimental conditions presently.

  7. Effect of Orally Administered Enterococcus faecium EF1 on Intestinal Cytokines and Chemokines Production of Suckling Piglets

    Directory of Open Access Journals (Sweden)

    Yi Huang§, Ya-li Li, Qin Huang, Zhi-wen Cui, Dong-you Yu, Imran Rashid Rajput, Cai-hong Hu and Wei-fen Li*

    2012-01-01

    Full Text Available The objective of this study was to determine the effect of orally administered Enterococcus faecium EF1 on intestinal cytokines and chemokines production in piglets. Twenty-four newborn piglets were randomly divided into two groups. The treatment group (T1, orally administered sterilized (110 ºC for 30 min skim milk 10% (2 ml/piglet/day with addition of viable E. faecium EF1 (5~6×108 cfu/ml on 1st, 3rd and 5th day after birth. The control group (T0, were fed the same volume of sterilized skim milk without addition of probiotics. Feeding trial was conducted for 25 days of suckling age. At the end of trail six piglets were randomly selected from each group to collect the samples of jejunum and ileum mucosa to observe the cytokines and chemokines production. The results showed that concentrations of IL-10 and TGF-β1 significantly increased in T1 group. Whereas, production of IL-1β, IL-6, IL-12, IFN-γ and IL-8 decreased in T1 compared to T0. Levels of TNF-α were increased in jejunal mucosa, while decreased in ileal mucosa comparatively in T1 group. Our findings revealed that oral administration of E. faecium EF1 induced a strong anti-inflammatory response in the small intestine. These immunomodulatory effects of this bacterium might contribute to maintenance of immune homeostasis in the intestine of piglets.

  8. Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats.

    Science.gov (United States)

    Musabayane, C T; Munjeri, O; Bwititi, P; Osim, E E

    2000-01-01

    We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.

  9. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.

    Science.gov (United States)

    Zgair, Atheer; Wong, Jonathan Cm; Lee, Jong Bong; Mistry, Jatin; Sivak, Olena; Wasan, Kishor M; Hennig, Ivo M; Barrett, David A; Constantinescu, Cris S; Fischer, Peter M; Gershkovich, Pavel

    2016-01-01

    There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines.

  10. Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs.

    Science.gov (United States)

    Bueno, L; Gue, M; Fargeas, M J; Alvinerie, M; Junien, J L; Fioramonti, J

    1989-04-01

    The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor.

  11. Extraction of Glycyrrhizic Acid and Glabridin from Licorice

    Directory of Open Access Journals (Sweden)

    Kyung Ho Row

    2008-04-01

    Full Text Available The extraction and separation conditions of glycyrrhizic acid and glabridin from licorice were investigated. By changing the different extraction solvents, procedures, times and temperature, the optimum extraction condition was established: the used of ethanol/water (30:70, v/v as an extraction solvent, and 60 min dipping time under 50°C. The extracts of licorice were separated and determined by reversed-phase high performance liquid chromatography with a methanol/water (70:30, v/v, containing 1% acetic acid as the mobile phase. Under the optimum extraction condition, 2.39 mg/g of glycyrrhizic acid and 0.92 mg/g of glabridin were extracted from Chinese licorice and the recoveries were 89.7% and 72.5% respectively.

  12. Extraction of Glycyrrhizic Acid and Glabridin from Licorice

    Science.gov (United States)

    Tian, Minglei; Yan, Hongyuan; Row, Kyung Ho

    2008-01-01

    The extraction and separation conditions of glycyrrhizic acid and glabridin from licorice were investigated. By changing the different extraction solvents, procedures, times and temperature, the optimum extraction condition was established: the used of ethanol/water (30:70, v/v) as an extraction solvent, and 60 min dipping time under 50°C. The extracts of licorice were separated and determined by reversed-phase high performance liquid chromatography with a methanol/water (70:30, v/v, containing 1% acetic acid) as the mobile phase. Under the optimum extraction condition, 2.39 mg/g of glycyrrhizic acid and 0.92 mg/g of glabridin were extracted from Chinese licorice and the recoveries were 89.7% and 72.5% respectively. PMID:19325770

  13. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

    Science.gov (United States)

    Jasion, Victoria S; Burnett, Bruce P

    2015-03-07

    Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

  14. A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease

    DEFF Research Database (Denmark)

    Keshav, Satish; Vaňásek, Tomáš; Niv, Yaron;

    2013-01-01

    CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 pat...... this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease....

  15. Efficacy of orally administered powdered aloe juice (Aloe ferox against ticks on cattle and ticks and fleas on dogs

    Directory of Open Access Journals (Sweden)

    J.J. Fourie

    2005-06-01

    Full Text Available The efficacy of orally administered powdered aloe juice (Aloe ferox was evaluated against ticks on cattle and against ticks and fleas on dogs. Twelve calves were each infested over a 25-day period with approximately 4000 larvae of Rhipicephalus (Boophilus decoloratus and allocated to 3 groups of 4 calves each. Three days after the last larval infestation and daily for 22 days thereafter, the calves in 1 group were fed 5 mg / kg body weight and those in another 25 mg / kg body weight of powdered aloe juice incorporated in game maintenance pellets, while the animals in the 3rd group received only pellets. Detached female ticks were collected daily and counted and the weights and the fertility of groups of 50 engorged female ticks collected from the animals were ascertained. The powdered aloe juice in the game maintenance pellets had no effect on the tick burdens of the calves or on the fertility of the ticks. Six dogs, in each of 2 groups, were treated daily for 15 consecutive days, commencing on Day -5 before the 1st tick infestation, with either 0.39 g or 0.74 g of powdered aloe juice, administered orally in gelatin capsules, while a 3rd group of 6 dogs served as untreated controls. All the dogs were challenged with Haemaphysalis leachi on Days 0 and +7, and with Ctenocephalides felis on Days+1and +8, and efficacy assessments were made 1 day after flea and 2 days after tick challenge, respectively. Treatment was not effective against ticks or fleas on the dogs.

  16. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  17. Bioavailability of orally administered rhGM-CSF: a single-dose, randomized, open-label, two-period crossover trial.

    Directory of Open Access Journals (Sweden)

    Wenping Zhang

    Full Text Available BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF. METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg and subcutaneously injected with rhGM-CSF (3.75 microg/kg respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of

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

    Directory of Open Access Journals (Sweden)

    Jian-yuan Li

    2014-01-01

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

  19. Correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis.

    Science.gov (United States)

    Liu, Wenlan; Sun, Zhirong; Qu, Jixu; Yang, Chunning; Zhang, Xiaomin; Wei, Xinxin

    2017-09-01

    The aim of the present study was to investigate the correlation between root respiration and the levels of biomass and glycyrrhizic acid in Glycyrrhiza uralensis. Root respiration was determined using a biological oxygen analyzer. Respiration-related enzymes including glucose-6-phosphate dehydrogenase plus 6-phosphogluconate dehydrogenase, phosphohexose isomerase and succinate dehydrogenase, and respiratory pathways were evaluated. Biomass was determined by a drying-weighing method. In addition, the percentage of glycyrrhizic acid was detected using high-performance liquid chromatography. The association between root respiration and the levels of biomass and glycyrrhizic acid was investigated. The glycolysis pathway (EMP), tricarboxylic acid cycle (TCA) and pentose phosphate (PPP) pathway acted concurrently in the roots of G. uralensis. Grey correlation analysis showed that TCA had the strongest correlation (correlation coefficient, 0.8003) with biomass. Starch and acetyl coenzyme A had the closest association with above-ground biomass, while soluble sugar correlated less strongly with above-ground biomass. Grey correlation analysis between biochemical pathways and the intermediates showed that pyruvic acid had the strongest correlation with EMP, while acetyl coenzyme A correlated most strongly with TCA. Among the intermediates and pathways, pyruvic acid and EMP exhibited the greatest correlation with glycyrrhizic acid, while acetyl coenzyme A and TCA correlated with glycyrrhizic acid less closely. The results of this study may aid the cultivation of G. uralensis. However, these results require verification in further studies.

  20. Diamagnetism and Strucure of Nitric Acid-Treated Bulk Polyethylene

    OpenAIRE

    Ania, F.; Baltá Calleja, F. J.; Cagiao, M.E.

    1982-01-01

    An alternative procedure to examine the nature of the end product of nitric-acid-treated bulk polyethylene involving the measurement of the diamagnetic susceptibility is reported. This simple non-destructive method complements previous results obtained by means of IR spectroscopy. Thus after selectively removing the surface layer of the polyethylene lamellae with nitric acid (t > 50h) the diamagnetic susceptibility substantially decreases to values wich are consistent with tilted paraff...

  1. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Lili eGao

    2015-10-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  2. Aggregation property of glycyrrhizic acid and its interaction with cyclodextrins analyzed by dynamic light scattering, isothermal titration calorimetry, and NMR.

    Science.gov (United States)

    Izutani, Yusuke; Kanaori, Kenji; Oda, Masayuki

    2014-06-17

    The structural properties of glycyrrhizic acid, a sweet-tasting constituent of Glycyrrhiza glabra, and its interaction with cyclodextrins were analyzed using dynamic light scattering, isothermal titration calorimetry, and NMR. The dynamic light scattering and NMR studies showed that glycyrrhizic acid forms a water-soluble aggregate that disperses upon the addition of γ-cyclodextrin. The high sweetness of glycyrrhizic acid can be closely correlated with this aggregation, because the multimers of glycyrrhizic acid can simultaneously bind to the sweet taste receptors on the human tongue. The isothermal titration calorimetry experiments demonstrated that γ-cyclodextrin binds to glycyrrhizic acid more strongly than β-cyclodextrin, however, both reactions are accompanied by a favorable change in binding entropy. Considering the large negative change in heat capacity that is observed during the binding of γ-cyclodextrin, the main driving force for the binding is hydrophobic interactions with dehydration, which is typical for inclusion complex. NMR experiments showed that γ-cyclodextrin interacts with the central part of the aglycone moiety, not the glucuronic acid moieties, resulting in high binding affinity. It should also be noted that the two distinct complexes of glycyrrhizic acid with γ-cyclodextrin would exist in aqueous solution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Interaction of aconitine with bovine serum albumin and effect of atropine sulphate and glycyrrhizic acid on the binding

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yun, E-mail: hy9317536@126.com [Pharmaceutical College, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang City, Hebei Province 050017 (China); Cui Lijian [Traditional Chinese Medical College, Hebei Medical University, Shijiazhuang 050091 (China); Wang Jianming; Huo Kun; Chen Chen; Zhan Wenhong; Wang Yongli [Pharmaceutical College, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang City, Hebei Province 050017 (China)

    2012-02-15

    The interaction of aconitine with bovine serum albumin (BSA) and effect of atropine sulphate and glycyrrhizic acid on binding constant, binding sites, and conformation were studied in an aqueous buffer solution (pH 7.40) by ultraviolet absorption and fluorescence spectroscopy. The study results show that aconitine quenched the endogenous fluorescence of BSA via a dynamic quenching procedure. Predominant intermolecular forces between aconitine and BSA were hydrophobic interactions, which stabilized the complex of aconitine-BSA. The distance between the donor and acceptor was 2.62 nm. The conformation of BSA was investigated by synchronous fluorescence techniques, indicating that the microenvironment around tryptophan (Trp) residues was changed. Furthermore, with the addition of atropine sulphate or glycyrrhizic acid, binding constant and the number of binding sites of aconitine to BSA were decreased, and the conformation had no change, which provide an important theoretical support for aconitine detoxification by atropine sulphate and glycyrrhizic acid. - Highlights: Black-Right-Pointing-Pointer Effect of atropine or glycyrrhizic acid on aconitine-BSA binding. Black-Right-Pointing-Pointer UV-vis absorption and fluorescence spectroscopic techniques used. Black-Right-Pointing-Pointer Aconitine quenched BSA fluorescence via dynamic quenching with r=2.62 nm. Black-Right-Pointing-Pointer Atropine sulphate and glycyrrhizic acid decreased K{sub A} and n of aconitine-BSA. Black-Right-Pointing-Pointer Support for aconitine detoxification by atropine and glycyrrhizic acid.

  4. Fecal Excretion of Orally Administered Collagen-Like Peptides in Rats: Contribution of the Triple-Helical Conformation to Their Stability.

    Science.gov (United States)

    Koide, Takaki; Yamamoto, Naoyuki; Taira, Kazuma B; Yasui, Hiroyuki

    2016-01-01

    Orally ingested peptides are generally digested in the gastrointestinal (GI) tract and absorbed in the form of oligopeptides. We previously reported that intravenously administered collagen-like triple-helical peptides circulated in the bloodstream and were excreted in their intact forms in urine nearly quantitatively. In the present study, we investigated the fates of orally administered collagen-like peptides in rats. (Pro-Hyp-Gly)10 (Hyp: 4-hydroxyproline), which formed a stable triple-helical structure, was stable in the GI tract, and 72.3±13.0% of the peptide was excreted in the feces. Its recovery ratio was similar to that of all-D-(Pro-Pro-Gly)10 (75.1±15.7%), the indigestible control. In contrast, (Pro-Hyp-Gly)5 and (Pro-Pro-Gly)10, the random coil conformations of which were dominant at body temperature, were not detected in fecal samples, indicating that they were digested by proteases. The high stability of the triple-helical conformation in mammalian bodies suggests the potential use of collagen-like peptides as novel scaffolds of peptide drugs.

  5. Intestinal interleukin-10 mobilization as a contributor to the anti-arthritis effect of orally administered madecassoside: a unique action mode of saponin compounds with poor bioavailability.

    Science.gov (United States)

    Wang, Ting; Wei, Zhifeng; Dou, Yannong; Yang, Yan; Leng, Dandan; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-03-01

    Madecassoside, a triterpenoid saponin present in Centella asiatica herbs with extremely low bioavailability, possesses excellent anti-rheumatoid arthritis property after oral administration. Such a disconnection between poor pharmacokinetic property and undoubted bioactivity also exists in many other herbal medicines. However, there is no reasonable explanation for this phenomenon to date. Here we showed that orally administered madecassoside displayed marked therapeutic effect on collagen-induced arthritis (CIA) in rats, which was accompanied by a systemic downregulation of inflammatory cytokines and an upregulation of anti-inflammatory cytokine IL-10. In vitro assays demonstrated that neither madecassoside nor its main metabolite madecassic acid could directly interfere with the secretion of inflammatory cytokines and IL-10. Intraperitoneal injection of madecassoside or madecassic acid was absent of significant effects on CIA progression, which further excluded the possibility of systemic action and highlighted the indispensable role of intestinal tracts. Notably, madecassoside could dramatically enhance the secretion of IL-10 from the small intestine of CIA rats probably through increasing the number of Foxp3(+) T lymphocytes in the lamina propria. In conclusion, madecassoside displays anti-arthritis property not by absorption into blood or by its metabolite, but through an intestine-dependent manner. The action can be mediated by, at least partially, the mobilization of IL-10 that originates from small intestines.

  6. Orally administered lactoperoxidase ameliorates dextran sulfate sodium-induced colitis in mice by up-regulating colonic interleukin-10 and maintaining peripheral regulatory T cells.

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    Shin, Kouichirou; Horigome, Ayako; Yamauchi, Koji; Yaeshima, Tomoko; Iwatsuki, Keiji

    2009-11-01

    We previously demonstrated orally administered bovine lactoperoxidase (LPO) ameliorated dextran sulfate sodium-induced colitis in mice. Here, we examine the mechanism of action of LPO. Three days after colitis induction, expression of interferon-gamma mRNA in colonic tissue was significantly decreased in mice administered LPO; while mRNA expression of interleukin (IL)-10 and regulatory T cell (Treg) marker, Foxp3, were significantly increased. The proportion of CD4+CD25+ Tregs in peripheral CD4+ T cells was also significantly elevated when LPO was administered. Nine days after colitis induction, the severity of colitis symptoms, including body weight loss and colon shortening, was reduced and expression of IL-10 mRNA was increased in mice administered LPO. The proportion of CD4+CD25+ Tregs in peripheral leukocytes was also significantly elevated when LPO was administered. These results suggest LPO ameliorates colitis by up-regulating colonic anti-inflammatory cytokines and maintaining peripheral regulatory T cells.

  7. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

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    Jenneke Leentjens

    Full Text Available RATIONALE: To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use. METHODS: We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity. RESULTS: β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan. CONCLUSION: The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01727895.

  8. Orally administered fructose increases the numbers of peripheral lymphocytes reduced by exposure of mice to gamma or SPE-like proton radiation

    Science.gov (United States)

    Romero-Weaver, A. L.; Ni, J.; Lin, L.; Kennedy, A. R.

    2014-07-01

    Exposure of the whole body or a major portion of the body to ionizing radiation can result in Acute Radiation Sickness (ARS), which can cause symptoms that range from mild to severe, and include death. One of the syndromes that can occur during ARS is the hematopoietic syndrome, which is characterized by a reduction in bone marrow cells as well as the number of circulating blood cells. Doses capable of causing this syndrome can result from conventional radiation therapy and accidental exposure to ionizing radiation. It is of concern that this syndrome could also occur during space exploration class missions in which astronauts could be exposed to significant doses of solar particle event (SPE) radiation. Of particular concern is the reduction of lymphocytes and granulocytes, which are major components of the immune system. A significant reduction in their numbers can compromise the immune system, causing a higher risk for the development of infections which could jeopardize the success of the mission. Although there are no specific countermeasures utilized for the ARS resulting from exposure to space radiation(s), granulocyte colony-stimulating factor (G-CSF) has been proposed as a countermeasure for the low number of neutrophils caused by SPE radiation, but so far no countermeasure exists for a reduced number of circulating lymphocytes. The present study demonstrates that orally administered fructose significantly increases the number of peripheral lymphocytes reduced by exposure of mice to 2 Gy of gamma- or SPE-like proton radiation, making it a potential countermeasure for this biological end-point.

  9. Time-and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid

    Institute of Scientific and Technical Information of China (English)

    Gang Cheng; Feng An; Mei-Juan Zou; Jin Sun; Xiu-Hua Hao; Yun-Xia He

    2004-01-01

    AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively.METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit[] L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied.RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium,but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets,5-ASA release was significantly governed by pH. Moreover,the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit[] L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release.CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

  10. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial.

    Science.gov (United States)

    Kasper, Siegfried; Gastpar, Markus; Müller, Walter E; Volz, Hans-Peter; Möller, Hans-Jürgen; Dienel, Angelika; Schläfke, Sandra

    2010-09-01

    This study was performed to investigate the anxiolytic efficacy of silexan, a new oral lavender oil capsule preparation, in comparison to placebo in primary care. In 27 general and psychiatric practices 221 adults suffering from anxiety disorder not otherwise specified (Diagnostic and Statistical Manual of Mental disorders-IV 300.00 or International Statistical Classification of Diseases and Related Health Problems, Tenth revision F41.9) were randomized to 80 mg/day of a defined, orally administered preparation from Lavandula species or placebo for 10 weeks with visits every 2 weeks. A Hamilton Anxiety Scale (HAMA) total score >or=18 and a total score >5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The primary outcome measures were HAMA and PSQI total score decrease between baseline and week 10. Secondary efficacy measures included the Clinical Global Impressions scale, the Zung Self-rating Anxiety Scale, and the SF-36 Health Survey Questionnaire. Patients treated with silexan showed a total score decrease by 16.0+/-8.3 points (mean+/-SD, 59.3%) for the HAMA and by 5.5+/-4.4 points (44.7%) for the PSQI compared to 9.5+/-9.1 (35.4%) and 3.8+/-4.1 points (30.9%) in the placebo group (Poil preparation had a significant beneficial influence on quality and duration of sleep and improved general mental and physical health without causing any unwanted sedative or other drug specific effects. Lavandula oil preparation silexan is both efficacious and safe for the relief of anxiety disorder not otherwise specified. It has a clinically meaningful anxiolytic effect and alleviates anxiety related disturbed sleep.

  11. Glycyrrhizic acid prevents enteritis through reduction of NF‑κB p65 and p38MAPK expression in rat.

    Science.gov (United States)

    Wang, Yi-Ming; Du, Guo-Qiang

    2016-04-01

    Glycyrrhizic acid has a variety of biological properties, including a protective function in the liver, and anti‑inflammatory, anti‑ulcer, anti‑anaphylaxis, anti‑oxidant, immunoregulatory, antiviral and anticancer activities. The efficacy of glycyrrhizic acid can be increased when combined with other medicines. In the present study, the potential protective effects of glycyrrhizic acid against enteritis in rats, and its role in regulating anti‑inflammation, anti‑oxidation, angiogenic and apoptotic mechanisms were investigated using enzyme‑linked immunosorbent and bicinchoninic acid assays, and reverse transcription‑quantitative polymerase chain reaction and western blotting analyses. Adult male Sprague‑Dawley rats were injected with 20 mg/kg methotrexate (MTX) to establish enteritis. Additionally, rats with MTX‑induced enteritis were peritoneally injected with 200 mg glycyrrhizic acid for 9 weeks. The current study demonstrated that glycyrrhizic acid could alleviate MTX‑induced increases of tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 levels, and raise IL‑10 levels, in rats with enteritis. Treatment with glycyrrhizic acid significantly reduced D‑lactate and intercellular adhesion molecule‑1 gene expression (Penteritis. Pretreatment with glycyrrhizic acid significantly suppressed the promotion of p38 mitogen‑activated protein kinase (p38MAPK), nuclear factor‑κB p65 (NF‑κB p65) protein expression, interferon‑γ protein concentration, and caspase‑3 and cycloxygenase‑2 activity in MTX‑induced enteritis (Penteritis by reducing NF‑κB p65 and p38MAPK expression levels, which may inform future therapeutic strategies for the treatment of enteritis.

  12. Enhancement of anti-inflammatory activity of glycyrrhizic acid by encapsulation in chitosan-katira gum nanoparticles.

    Science.gov (United States)

    Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

    2016-08-01

    Efforts were made to improve the bioavailability and efficacy of Glycyrrhizic acid, a triterpentine saponin obtained from Glycyrrhiza glabra, having several pharmacological properties, by its encapsulation in biocompatible biopolymeric nanoparticles. Polycationic chitosan and polyanionic gum katira were used to prepare nanoparticles by ionic complexation method. Glycyrrhizic acid was loaded into the nanoparticles and was then examined for change in its in vivo anti-inflammatory activity against carrageenan-induced rat hind paw inflammation. The effects of concentrations of glycyrrhizic acid, chitosan and katira gum, upon particle size and encapsulation efficiency of glycyrrhizic acid were studied with the help of response surface methodology employing 3-factor, 3-level central composite experimental design. Particle size and encapsulation efficiency of optimized nanoparticulate formulation were 175.8nm and 84.77%, respectively. Particles were observed in transmission electron microscopy to be spherical in shape and 80nm in size. FTIR analysis indicated electrostatic interactions between carboxyl groups of ammonium glycyrrhizinate and amino groups of chitosan. In vitro drug release studies indicated that glycyrrhizic acid was released from the nanoparticles following zero-order kinetics and that there was a sustained release of the drug with 90.71% of it being released over a 12h period, and that the mechanism of release of glycyrrhizic acid from the nanoparticles was a combination of diffusion and erosion of the polymer matrix. In-vivo anti inflammatory efficacy of glycyrrhizic acid clearly improved upon encapsulation in chitosan-katira gum nanoparticles, by overcoming the limited bioavailability of its other forms.

  13. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C

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    Villena Julio

    2012-09-01

    Full Text Available Abstract Background Some studies have shown that probiotics, including Lactobacillus rhamnosus CRL1505, had the potential to beneficially modulate the outcome of certain bacterial and viral respiratory infections. However, these studies did not determine the mechanism(s by which probiotics contribute to host defense against respiratory viruses. Results In this work we demonstrated that orally administered Lactobacillus rhamnosus CRL1505 (Lr1505 was able to increase the levels of IFN-γ, IL-10 and IL-6 in the respiratory tract and the number of lung CD3+CD4+IFN-γ+ T cells. To mimic the pro-inflammatory and physiopathological consecuences of RNA viral infections in the lung, we used an experimental model of lung inflammation based on the administration of the artificial viral pathogen-associated molecular pattern poly(I:C. Nasal administration of poly(I:C to mice induced a marked impairment of lung function that was accompanied by the production of pro-inflammatory mediators and inflammatory cell recruitment into the airways. The preventive administration of Lr1505 reduced lung injuries and the production of TNF-α, IL-6, IL-8 and MCP-1 in the respiratory tract after the challenge with poly(I:C. Moreover, Lr1505 induced a significant increase in lung and serum IL-10. We also observed that Lr1505 was able to increase respiratory IFN-γ levels and the number of lung CD3+CD4+IFN-γ+ T cells after poly(I:C challenge. Moreover, higher numbers of both CD103+ and CD11bhigh dendritic cells and increased expression of MHC-II, IL-12 and IFN-γ in these cell populations were found in lungs of Lr1505-treated mice. Therefore, Lr1505 treatment would beneficially regulate the balance between pro-inflammatory mediators and IL-10, allowing an effective inflammatory response against infection and avoiding tissue damage. Conclusions Results showed that Lr1505 would induce a mobilization of cells from intestine and changes in cytokine profile that would be able to

  14. Absorptive constituents and their metabolites in drug-containing urine samples from Wuzhishan miniature pigs orally administered with Buyang Huanwu decoction.

    Science.gov (United States)

    Yang, Dong-Hui; Ren, Xiang-Liang; Xu, Feng; Ma, Xiao-Qing; Liu, Guang-Xue; Li, Cang-Hai; Li, Chen; Cai, Shao-Qing

    2014-01-01

    Buyang Huanwu decoction (BYHWD), a famous traditional Chinese medicine prescription for the treatment of cerebrovascular diseases, is composed of seven commonly used Chinese herbs--Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Chuanxiong Rhizoma, Carthami Flos, Persicae Semen and Pheretima. To determine the main absorptive constituents and the metabolites of BYHWD in vivo, urine samples from Wuzhishan (WZS) miniature pigs orally administered with BYHWD (13.6 g crude drugs/kg) were collected to investigate the characteristic compounds. By comparing the high-performance liquid chromatography of a drug-containing urine sample with that of a drug-free sample, 17 characteristic compounds were isolated from the methanol extract of a drug-containing urine sample by column chromatography. Their structures, including 11 isoflavanoids, 2 pterocarpanoids and 4 isoflavonoids, were identified by spectroscopic means. Of the 17 compounds, 8 (1-8) were new compounds with the following structures: 3S-7,3',4'-trihydroxyisoflavan-3'-O-β-D-glucuronide (1), 3S-7,3',4'-trihydroxyisoflavan-4'-O-β-D-glucuronide (2), 3S-7,2',4'-trihydroxyisoflavan-2'-O-β-D-glucuronide (3), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-2'-O-β-D-glucuronide (4), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-2'-O-β-D-glucuronide-6"-methyl ester (5), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-β-D-glucuronide-6"-methyl ester (6), 3R-7,2',3'-trihydroxy-4'-methoxyisoflavan-3'-O-β-D-glucuronide-6"-methyl ester (7), and 3S-7,4',5'-trihydroxy-2',3'-dimethoxyisoflavan-5'-O-β-D-glucuronide (8). Based on the possible relationship and metabolic pathways of the 17 compounds in vivo, 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan (isomucronulatol, 11), 6aR,11aR-3-hydroxy-9,10-dimethoxypterocarpan (methylnissolin, astrapterocarpan, 13), 7,3'-dihydroxy-4'-methoxyisoflavone (calycosin, 16) and 7-hydroxy-4'-methoxyisoflavone (formononetin, 17) were thought to be the most important absorptive original

  15. Effects of SiC nanoparticles orally administered in a rat model: Biodistribution, toxicity and elemental composition changes in feces and organs

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Omar, E-mail: omar.lozanogarcia@fundp.ac.be [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Laloy, Julie; Alpan, Lütfiye [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Mejia, Jorge [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Research Centre for the Physics of Matter and Radiation (PMR-LARN), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Rolin, Stéphanie [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Toussaint, Olivier [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Laboratory of Biochemistry and Cellular Biology (URBC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); Dogné, Jean-Michel [Namur Nanosafety Center (NNC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur - FUNDP, Rue de Bruxelles 61, B-5000 Namur (Belgium); Department of Pharmacy, NAMEDIC, Namur Thrombosis and Hemostasis Center (NTHC), University of Namur (FUNDP), Rue de Bruxelles 61, B-5000 Namur (Belgium); and others

    2012-10-15

    Background: Silicon carbide (SiC) presents noteworthy properties as a material such as high hardness, thermal stability, and photoluminescent properties as a nanocrystal. However, there are very few studies in regard to the toxicological potential of SiC NPs. Objectives: To study the toxicity and biodistribution of silicon carbide (SiC) nanoparticles in an in vivo rat model after acute (24 h) and subacute (28 days) oral administrations. The acute doses were 0.5, 5, 50, 300 and 600 mg·kg{sup −1}, while the subacute doses were 0.5 and 50 mg·kg{sup −1}. Results: SiC biodistribution and elemental composition of feces and organs (liver, kidneys, and spleen) have been studied by Particle-Induced X-ray Emission (PIXE). SiC and other elements in feces excretion increased by the end of the subacute assessment. SiC did not accumulate in organs but some elemental composition modifications were observed after the acute assessment. Histopathological sections from organs (stomach, intestines, liver, and kidneys) indicate the absence of damage at all applied doses, in both assessments. A decrease in the concentration of urea in blood was found in the 50 mg·kg{sup −1} group from the subacute assessment. No alterations in the urine parameters (sodium, potassium, osmolarity) were found. Conclusion: This is the first study that assesses the toxicity, biodistribution, and composition changes in feces and organs of SiC nanoparticles in an in vivo rat model. SiC was excreted mostly in feces and low traces were retrieved in urine, indicating that SiC can cross the intestinal barrier. No sign of toxicity was however found after oral administration. -- Highlights: ► SiC nanoparticles were orally administered to rats in acute and subacute doses. ► SiC was found in low traces in urine. It is mostly excreted in feces within 5 days. ► SiC excretion rate, feces and organ elemental composition change with time. ► No morphological alteration were found on GI tract, liver, kidneys

  16. Orally administered fatty acids enhance anorectic potential but do not activate central fatty acid sensing in Senegalese sole post-larvae.

    Science.gov (United States)

    Velasco, Cristina; Bonacic, Kruno; Soengas, José L; Morais, Sofia

    2017-02-15

    Studies in fish have reported the presence and function of fatty acid (FA)-sensing systems comparable in many aspects to those known in mammals. Such studies were carried out in juvenile and adult fish, but the presence of FA-sensing systems and control of food intake have never been evaluated in early life stages, despite the importance of establishing when appetite regulation becomes functional in larval fish. In this study, we aimed to elucidate the possible effects of different specific FAs on neural FA-sensing systems and neuropeptides involved in the control of food intake in Senegalese sole post-larvae. To achieve this, we orally administered post-larvae with different solutions containing pure FA - oleate (OA), linoleate (LA), α-linolenate (ALA) or eicosapentaenoate (EPA) - and evaluated changes in mRNA abundance of neuropeptides involved in the control of food intake and of transcripts related to putative FA-sensing systems, 3 and 6 h post-administration. The changes in neuropeptide gene expression were relatively consistent with the activation of anorectic pathways (enhanced cart4 and pomcb) and a decrease in orexigenic factors (npy) following intake of FA. Even though there were a few differences depending on the nature of the FA, the observed changes appear to suggest the existence of a putative anorectic response in post-larvae fish to the ingestion of all four tested FAs. However, changes in neuropeptides cannot be explained by the integration of metabolic information regarding FAs in circulation through FA-sensing mechanisms in the brain. Only the reduction in mRNA levels of the FA metabolism gene acc in OA-treated (6 h), ALA-treated (3 h) and EPA-treated (3 and 6 h) post-larvae could be indicative of the presence of a FA-sensing system, but most genes either were not significantly regulated (fat/cd36-lmp2, acly, kir6.x, srebp1c) or were affected in a way that was inconsistent with FA-sensing mechanisms (fat/cd36-pg4l, fas, cpt1.1, cpt1

  17. Pharmacokinetic Effects of Cinnamic Acid, Amygdalin, Glycyrrhizic Acid and Liquiritin on Ephedra Alkaloids in Rats.

    Science.gov (United States)

    Tang, Yinghong; Zheng, Mengkai; Chen, Yu-Lin; Chen, Jianzhen; He, Yu

    2017-06-01

    Ephedra alkaloids, including ephedrine (EP), pseudoephedrine (PEP) and methylephedrine (MEP), are sympathomimetic compounds with known toxicities but many Ephedra (Ephedrae herba) preparations, such as Ephedra decoction, have been clinically applied for centuries. In order to explore the possible detoxification mechanism of Ephedra alkaloids, four representative compounds in Ephedra decoction (cinnamic acid, amygdalin, glycyrrhizic acid and liquiritin) were studied for their pharmacokinetic effects on Ephedra alkaloids in Sprague-Dawley rats. Animals were randomly divided into six groups, with six rats in each. Rats were treated orally with EP-PEP-MEP (20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP) and different combinations of cinnamic acid (3.03 mg/kg), amygdalin (56.97 mg/kg), glycyrrhizic acid (12.42 mg/kg), liquiritin (3.79 mg/kg) with EP-PEP-MEP, and 20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP + 3.03 mg/kg cinnamic acid + 56.97 mg/kg amygdalin + 12.42 mg/kg glycyrrhizic acid + 3.79 mg/kg liquiritin. Blood samples (0.5 mL) were taken from the orbital sinus venous plexus into heparinized tubes at 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min (6 rats per time point in each group) following single administration. The concentrations of Ephedra alkaloids in rat plasma were determined using a validated high performance liquid chromatography method. Area under the concentration-time curve from 0 to 360 min (AUC0-t ) of EP, PEP and MEP were 666.99, 650.76 and 632.37 µg·min/mL, respectively. Maximum plasma concentration (C max) of EP, PEP and MEP were 4.15, 4.08 and 3.59 μg/mL, respectively. Mean residence time (MRT) of EP, PEP and MEP were 197.00, 173.97 and 183.87 min, respectively, when the rats were treated with EP-PEP-MEP. Cinnamic acid increased the AUC0-t of EP while decreased C max of EP, amygdalin and glycyrrhizic acid increased C max and AUC0-t of EP and PEP, while liquiritin decreased AUC0-t of EP and PEP. The

  18. Enrichment of the Glycyrrhizic Acid from Licorice Roots (Glycyrrhiza glabra L. by Isoelectric Focused Adsorptive Bubble Chromatography

    Directory of Open Access Journals (Sweden)

    Eyyüp Karaoğul

    2016-01-01

    Full Text Available The main aim of this study was to enrich glycyrrhizic acid ammonium salt known as one of the main compounds of licorice roots (Glycyrrhiza glabra L. by isoelectric focused adsorptive bubble separation technique with different foaming agents. In the experiments, four bubble separation parameters were used with β-lactoglobulin, albumin bovine, and starch (soluble preferred as foaming agents and without additives. The enrichment of glycyrrhizic acid ammonium salt into the foam was influenced by different additive substances. The results showed that highest enrichment values were obtained from β-lactoglobulin as much as 368.3 times. The lowest enrichment values (5.9 times were determined for the application without additive. After enrichment, each experiment of glycyrrhizic acid ammonium salt confirmed that these substances could be quantitatively enriched into the collection vessel with isoelectric focused adsorptive bubble separation technique. The transfer of glycyrrhizic acid ammonium salt into the foam from standard solution in the presence of additive was more efficient than aqueous licorice extract.

  19. Simultaneous determination of 12, 13-dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture by high performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    Zhi-Sheng Xie; Xin-Jun Xu; Chun-Yan Xie; Jie-Yun Huang; Mei Yang; Rui-Ming Li; Xiao Chen

    2011-01-01

    A reversed phase high performance liquid chromatography (HPLC) method was established for the simultaneous determination of 12, 13-dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture. A Grace Apollo Cl8 column (250 mm × 4.6 mm, 5 μm) was used as the stationary phase and the mobile phase was composed of acetonitrile and aqueous phosphoric acid (0.2%, v/v). Gradient elution was carried out at the flow rate of 1.0 mL/min and the column temperature was 30 ℃. An ultraviolet (UV) detector was used with a selected wavelength of 240 nm. Calibration curves were linear within the concentration range of 4.6-45.75 μg/mL for 12, 13-dihydroxyeuparin (r〉0.9999) and 106.9-1068.9μg/mL for glycyrrhizic acid (r〉0.9999), respectively. Recoveries were 102.18% for 12, 13-dihydroxyeuparin and 101.17% for glycyrrhizic acid. The method developed could be applied to the simultaneous determination of 12, 13- dihydroxyeuparin and glycyrrhizic acid in Yanyanfang mixture.

  20. In Vitro Co-Delivery Evaluation of Novel Pegylated Nano-Liposomal Herbal Drugs of Silibinin and Glycyrrhizic Acid (Nano-Phytosome to Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ochi Mohammad Mahdi

    2016-07-01

    Full Text Available Objective This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma (HCC cell line (HepG2. Materials and Methods In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude. Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine (DPPC, cholesterol (CHOL, and methoxy-polyethylene glycol 2000 (PEG2000–derived distearoyl phosphatidylethanolamine (mPEG2000-DSPE. We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin (25% w/v and glycyrrhizic acid (75% w/v on HepG2 and fibroblast cell lines over a 48-hour period. Results Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency (EE for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results of in vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration (IC50 for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 µg/ml and free silibinin with glycyrrhizic acid was 485.45 µg/ml on the HepG2 cell line. Conclusion This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line.

  1. Modulation of genotoxicity of oxidative mutagens by glycyrrhizic acid from Glycyrrhiza glabra L.

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    Prabhjit Kaur

    2012-01-01

    Full Text Available Background: The chemopreventive effects of certain phytoconstituents can be exploited for their use as functional foods, dietary supplements and even as drugs. The natural compounds, acting as anti-genotoxic and free radical scavenging compounds, may serve as potent chemopreventive agents. These can inhibit DNA modulatory activities of mutagens and help preventing pathological processes. Objectives: Present study on Glycyrrhiza glabra L., a promising medicinal plant, widely used in traditional medicine, focused on the bioassay-guided fractionation of its extracts for the isolation of certain phytochemicals with anti-genotoxic potential against oxidative mutagens. Materials and Methods: The methanol extract of Glycyrrhiza glabra rhizomes was subjected to column chromatography, and isolated fraction was evaluated for its anti-genotoxic and antioxidant potential using SOS chromotest, Comet assay, and DPPH radical scavenging assay. Results: GLG fraction, which was characterized as Glycyrrhizic acid, inhibited the genotoxicity of oxidative mutagens viz., H 2 O 2 and 4NQOquite efficiently. In SOS chromotest, using E.coli PQ37 tester strain, it inhibited induction factor induced by H 2 O 2 and 4NQO by 75.54% and 71.69% at the concentration of 121.46 μM,respectively. In Comet assay, it reduced the tail moment induced by H 2 O 2 and 4NQO by 70.21% and 69.04%, respectively, at the same concentration in human blood lymphocytes. The isolated fraction also exhibited DPPH free radical scavenging activity and was able to scavenge 85.95% radicals at a concentration of 120 μM. Conclusion: Glycyrrhizic acid is a potential modulator of genotoxins as well as efficient scavenger of free radicals.

  2. Physicochemical and structural properties of glycerin gel prepared using glycyrrhizic acid diethyl ester.

    Science.gov (United States)

    Koga, Kenjiro; Kimura, Toshiyuki; Sakai, Kenichi; Kushida, Hiroshi; Yoshikawa, Nobuji

    2014-01-01

    Glycyrrhizic acid diethyl ester (GZ-DE) was developed as a prodrug of glycyrrhizic acid (GZ), a hepatitis therapeutic drug. We fortuitously found that GZ-DE gels with glycerin selectively while searching for a safe solvent with which to dissolve GZ-DE. Based on this gelation, the aim of this study was to investigate the preparation of the gel and study the rheology, physicochemical and structural properties of the glycerin gel by differential scanning calorimeter (DSC), capillary electrophoresis (CEP), nuclear magnetic resonance (NMR), and small angle X-ray scattering (SAXS). The glycerin gel was prepared by the addition of at least 2.0% w/w GZ-DE. This gel did not flow at room temperature. After mixing glycerin and GZ-DE, a gel was formed after 2 days at 25°C or 3 h at 60°C. Glycerin gel containing 2.4% w/w GZ-DE provided the following results: 1) The glycerin gel exhibited creep at a constant stress of less than 10 Pa, but it is a fragile gel, showing Newtonian flow at 10 Pa stress. 2) Dynamic viscoelastic measurements showed that the elastic modulus (G') exceeds the viscous modulus (G''), indicating that glycerin gel has solid-like properties. 3) DSC showed a significant difference between the glass transition temperature of glycerin and glycerin gel. 4) CEP did not reveal a new compound in the glycerin gel. 5) NMR confirmed that glycerin gel is a physical gel. 6) SAXS measurements revealed that the glycerin gel has an oval-shaped basic frame (119 nm long and 65 nm wide).

  3. Effect of acid treated carbon nanotubes on mechanical, rheological and thermal properties of polystyrene nanocomposites

    KAUST Repository

    Amr, Issam Thaher

    2011-09-01

    In this work, multiwall carbon nanotubes (CNT) were functionalized by acid treatment and characterized using Fourier Transform Infrared Spectroscopy (FTIR) and thermogravimetric analysis (TGA). Polystyrene/CNT composites of both the untreated and acid treated carbon nanotubes were prepared by thermal bulk polymerization without any initiator at different loadings of CNT. The tensile tests showed that the addition of 0.5 wt.% of acid treated CNT results in 22% increase in Young\\'s modulus. The DSC measurements showed a decrease in glass transition temperature (Tg) of PS in the composites. The rheological studies at 190 °C showed that the addition of untreated CNT increases the viscoelastic behavior of the PS matrix, while the acid treated CNT acts as plasticizer. Thermogravimetric analysis indicated that the incorporation of CNT into PS enhanced the thermal properties of the matrix polymer. © 2011 Elsevier Ltd. All rights reserved.

  4. Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances when used as a flavouring for all animal species

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP

    2015-01-01

    Full Text Available Glycyrrhizic acid is extracted from the dried and ground rhizome and root portions of the perennial leguminous plant Glycyrrhiza glabra L., native to southern Europe and Central Asia, or other species of the genus Glycyrrhiza. It is currently listed in the register of flavouring substances, allowing its use in food without restriction. Glycyrrhyzic acid ammoniated is safe at the concentration of 1 mg/kg complete feed for all species, except chickens for fattening and laying hens. For these two categories, a safe concentration of 0.3 mg/kg complete feed applies. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP cannot conclude on the safety of the additive used in water for drinking. The FEEDAP Panel considers that the use of glycyrrhizic acid ammoniated in animal nutrition would not measurably increase consumer exposure. In the absence of data on user safety, the FEEDAP Panel considers it prudent to treat glycyrrhizic acid ammoniated as an irritant to skin, eyes and respiratory tract and as a skin sensitiser. The use of glycyrrhizic acid ammoniated in animal feeds would not pose a risk to the environment. As glycyrrhizic acid ammoniated is used in food as a flavouring, no further demonstration of efficacy is necessary.

  5. Orally Administered Bioadherent Sustained Release Microencapsulated Vaccines

    Science.gov (United States)

    1996-09-01

    microspheres consist of bovine serum albumin (BSA) and recombinant vitelline protein B (vpB) from the liver fluke Fasciola hepatica which is a known...from the liver fluke Fasciola hepatica ." Biochemistry 26, 7819-7825. 10. Waite, J.H., Rice-Ficht, A.C. (1992) "Eggshell precursor proteins of Fasciola ...precursor proteins of Fasciola hepatica : I. Structure and expression of vitelline protein B." Mol. Bioch. Parasitol. 54, 127-143. 12. Yapel, A.F. (1985

  6. Explication of Definitional Description and Empirical Use of Fraction of Orally Administered Drugs Absorbed From the Intestine (Fa) and Intestinal Availability (Fg): Effect of P-glycoprotein and CYP3A on Fa and Fg.

    Science.gov (United States)

    Tanaka, Yuta; Kitamura, Yoshiaki; Maeda, Kazuya; Sugiyama, Yuichi

    2016-02-01

    Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and Fa and Fg are often used without careful definition. In this review, Fa and Fg are mathematically described based on their definitions under the linear kinetics of metabolism and transport. Even considering with different models, intestinal metabolic enzymes such as cytochrome P450 3A affected both Fa and Fg, whereas apical efflux transporters including P-glycoprotein had no influence on Fg at least under the linear condition. To determine whether Fa and Fg calculated using different clinical methods are identical, empirical Fa and Fg were mathematically described based on "feces method" and "grapefruit juice method" and compared with their definitions. Fa and Fg obtained by the feces method corresponded with their definitions whereas the grapefruit juice method provided smaller Fa and larger Fg particularly for dual substrates of P-glycoprotein and cytochrome P450 3A with low membrane permeability. Our analyses suggest that the definitions and calculation methods of Fa and Fg should be considered when we intend to separately determine these values.

  7. Removal Cu(II ions from water using sulphuric acid treated Lagenaria vulgaris Shell (Cucurbitaceae

    Directory of Open Access Journals (Sweden)

    Ljupković, R.B.

    2011-09-01

    Full Text Available Removal of Cu(II ions from water solutions by sulphuric acid treated Lagenaria vulgaris shell (ccLVB was studied. Batch experiments were done by shaking a fixed mass of biosorbent (1.0 g with 250 cm3 of 50.0 mg dm–3 Cu(II solutions, at pH ranged from 2 up to 6. Metal concentration in the filtrates as well as in the initial solution was determined by flame atomic absorption spectrometry. Results show that efficiency of Cu(II ions uptake by sulphuric acid treated Lagenaria vulgaris shell is significantly greater than raw Lagenaria vulgaris biosorbent. In addition, there is no significant effect of initial pH of solution on Cu(II ions uptake by ccLVB and obtained biosorbent can be applied in a wide range of pH.

  8. [Simultaneous determination of stevioside, rebaudioside A and glycyrrhizic acid in foods by HPLC].

    Science.gov (United States)

    Sakamaki, Narue; Matsumoto, Hiroko; Hagino, Kayo; Nakazato, Mitsuo; Yasuda, Kazuo

    2004-04-01

    A method for the simultaneous determination of stevioside (Stev), rebaudioside A (RebA) and glycyrrhizic acid (GA) in foods was developed. These sweeteners were extracted from foods, except for dried fishes and shellfishes, by dialysis against Tris-HCl buffer (pH 9.0). Dried fishes and shellfishes were extracted with Tris-HCl buffer--methanol (2:8). The extracts were cleaned up with an Oasis MAX cartridge. The cartridge was washed with 0.05 mol/L sodium acetate (pH 4.0)--methanol (19:1), and the three sweeteners were eluted with 0.1 mol/L phosphoric acid--acetonitrile (1:1). Stev, RebA and GA in the eluate were chromatographed on a Develosil RPAQUEOUS-AR-5 (4.6 mm i.d. x 250 mm) column with 0.02 mol/L phosphoric acid-acetonitrile--methanol (90:55:5) as a mobile phase and monitored at 210 nm for Stev and RebA, and at 254 nm for GA. The recoveries of Stev, RebA and GA from 8 kinds of foods spiked at the level of 0.1 g/kg were 81.7-101%, 81.5-100% and 78.6-95.0%, respectively. The determination limits were 0.01 g/kg in samples.

  9. Preparation of Glycyrrhetinic Acid Monoglucuronide by Selective Hydrolysis of Glycyrrhizic Acid via Biotransformation

    Institute of Scientific and Technical Information of China (English)

    LU Li; MA Bai-ping; ZHAO Yang; YU He-shui; HUANG Hong-zhi; KANG Li-ping; CAO Man; CUI Jiang-ming; YU Li-yan; SONG Xin-bo

    2012-01-01

    Objective To search for the microorganisms which have the high selectivity of hydrolyzing glycyrrhizic acid(GL)into 18β-glycyrrhetinic acid-3-O-β-D-glucuronide(GAMG)without glycyrrhetinic acid(GA)byproduct.Methods GL was biotransformed by Aspergillus sp.,the products were separated by chromatography on reverse phase C18 column and semi-preparative HPLC,and their structures were elucidated on the basis of HR-ESI-MS,1D NMR(1H-NMR,13C-NMR,and NOESY)and 2D NMR(1H-1H COSY,HSQC,and HMBC)spectral analyses.Results Aspergillus sp.could partially hydrolyze GL into GAMG(3),along with two minor byproducts,3-O-β-D-glucurono-pyranosyl-18β-liquiritic acid(1)and 3-O-β-D-glucuronopyranosyl-24-hydroxy-18β-glycyrrhetinic acid(2).Conclusion Aspergillus sp.has the high selectivity of hydrolyzing GL into GAMG without GA byproduct and the yield of GAMG is about 60%.The complete assignments of 1H-NMR and 13C-NMR data for compounds 1 and 2 are reported for the first time.

  10. Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism.

    Science.gov (United States)

    Singh, Kailash; Zaw, Aung Moe; Sekar, Revathi; Palak, Ahuja; Allam, Ahmed A; Ajarem, Jamaan; Chow, Billy K C

    2016-09-27

    Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2 adrenergic receptor remains constant during the risk of heart failure. Beta blockers-the antagonistic molecules for beta-adrenergic receptors, function by slowing the heart rate, which thereby allows the left ventricle to fill completely during tachycardia incidents and hence helps in blood pumping capacity of heart and reducing the risk of heart failure. In the present study, we investigate the potential of glycyrrhizic acid (GA) as a possible principal drug molecule for cardiac arrhythmias owing to its ability to induce reduction in the heart rate and blood pressure. We use in vitro and in silico approach to study GA's effect on beta adrenergic receptor along with an in vivo study to examine its effect on heart rate and blood pressure. Additionally, we explore GA's proficiency in eliciting an increase in the plasma levels of vasoactive intestinal peptide, which by dilating the blood vessel consequently, can be a crucial aid during the occurrence of a potential heart attack. Therefore, we propose GA as a potential principal drug molecule via its potential in modulating heart rate and blood pressure.

  11. Effects of Glycyrrhizic Acid on Productive and Immune Parameters of Broilers

    Directory of Open Access Journals (Sweden)

    CL Ocampo

    Full Text Available ABSTRACT Considering that glycyrrhizic acid (GRA has been shown to have in-vitro and in-vivo antiviral activity against a wide range of viruses as well as immunostimulating activity, a trial to evaluate its effects on the performance and the immune response against Newcastle disease of broiler chickens was carried out. The study was performed with one-day-old Ross x Ross broiler chickens. GRA was added to the drinking water throughout the 49-d production cycle at a dose of 0.03%. Sample size of the trial was established in a pilot assay. Results showed that broiler chickens treated with GRA presented better weight gain, final body weight, feed conversion ratio, and lower mortality rate than the non-treated controls. In addition, GRA-treated birds presented higher antibody titers against Newcastle disease virus and more efficient cellular immune response, as demonstrated by the late-hypersensitivity response test. Blood lymphocyte and thrombocyte counts also increased in this group. The histopathological examination of the bursa, spleen, and thymus revealed that only the thymus of the GRA-treated group had a clearly defined increase in cortex thickness on day 49. The bursa showed a higher number of lymphoid lesions in CG on days 21 and 49 compared with the GRA group. These results suggest that GRA has growth promotion properties, which are possibly linked to immune-based effects.

  12. Efficacy of Albendazole Orally Administered at Different Dosages against Trichinella spiralis Encapsulated Larvae in Mice%口服阿苯达唑抗小鼠旋毛虫成囊期幼虫的效果观察

    Institute of Scientific and Technical Information of China (English)

    李润花; 裴彦江; 李起超; 霍将; 丁宇; 殷国荣

    2012-01-01

    Objective To evaluate the efficacy of albendazole (ABZ) orally administered at different dosages against Trichinella spirails encapsulated larvae in striated muscle in mice. Methods A total of 72 BALB/c mice were divided equally into 9 groups. Each mouse was infected orally with 50 T. Spiralis encapsulated larvae. At the 29th day after infection, albendazole was each orally administered to the mice of the 8 groups with doses of 50, 100, 150, 200, 250, 300, 350, and 400mg/(kg·d), respectively, once a day at fixed time for 6d. The control group was untreated. Mice were sacrificed at the 7lh day post administration. The encapsulated larvae in diaphragmatic muscle, jugomaxillary muscle and gastrocnemius muscle were examined with pellet method. The encapsulated larva that the capsule was complete and the larva inside curled naturally with clear structure was considered survived. The therapeutic effect was estimated on the average quantity of total, survival and dead encapsulated larvae per gram muscle, total worm reduction and survival worm reduction. Results The total worm burden and survival worms showed a decreasing trend and the numbers of dead worms increased in diaphragmatic muscle, jugomaxillary muscle and gastrocnemius muscle when the dosage of albendazole were 50-250 mg/(kg·d), but the number of larvae in the muscles remained similar when the dosage of albendazole was greater than 250mg/kg·d. Compared with the control group, the total and survival worms in the muscles in 200mg/(kg·d) and the greater dose groups decreased significantly (P<0.01). In 250 mg/(kg·d) group the total worm reduction in jugomaxillary muscle, diaphragmatic muscle and gastrocnemius muscle were 50.00%, 62.62% and 57.48%, and the survival worm reduction were 79.96%, 83.25% and 80.56%, respectively. Conclusion Orally administered to mice for 6d, albendazole at 250mg/(kg·d) is a suitable dose against encapsulated larva stage of T. Spiralis in muscle.%目的 观察口服不同剂量阿

  13. Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice.

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    Roberta Vitali

    Full Text Available High mobility group box-1 (HMGB1 is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation.This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG is a good strategy to reduce intestinal inflammation.Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS; a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses.DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG.HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation.

  14. Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice

    Science.gov (United States)

    Vitali, Roberta; Palone, Francesca; Cucchiara, Salvatore; Negroni, Anna; Cavone, Leonardo; Costanzo, Manuela; Aloi, Marina; Dilillo, Anna; Stronati, Laura

    2013-01-01

    Background High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation. Aim This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG) is a good strategy to reduce intestinal inflammation. Methods Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS); a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses. Results DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG. Conclusions HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation. PMID:23840500

  15. Effect of glycyrrhizic acid on titanium dioxide nanoparticles-induced hepatotoxicity in rats.

    Science.gov (United States)

    Orazizadeh, Mahmoud; Fakhredini, Fereshtesadat; Mansouri, Esrafil; Khorsandi, Layasadat

    2014-09-05

    Many recent studies demonstrate that most nanoparticles (NPs) have an adverse or toxic action on liver. The aim of this study was to investigate the hepatoprotective effect of glycyrrhizic acid (GA) against hepatic injury induced by titanium dioxide nanoparticles (NTiO2) in rats. Thirty-two Wistar rats were randomly divided into 4 groups. NTiO2-intoxicated rats received 300 mg/kg of NTiO2 for 14 days by gavage method. Protection group pretreated with GA for 7 days before NTiO2 administration. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected as biomarkers in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were evaluated for oxidative stress in hepatic injury. Light microscopy for histopathological studies and TUNEL assay was also done. Administration of NTiO2 induced a significant elevation in plasma AST, ALT and ALP. In the liver, NTiO2 increased oxidative stress through the increase in lipid peroxidation and decrease in SOD and GPx enzymes. Histopathological studies showed that treatment with NTiO2 caused liver damage including centrilobular necrosis, which was accompanied by congestion and accumulation of inflammatory cells. Apoptotic index was also significantly increased in this group. Pretreatment of GA significantly decreased ALT, AST and ALP, attenuated the histopathology of hepatic injury, decreased apoptotic index, ameliorated oxidative stress in hepatic tissue, and increased the activities of SOD and GPx. These findings indicate that GA effectively protects against NTiO2-induced hepatotoxicity. GA has a potent protective effect against the NPs induced hepatotoxicity and might be clinically useful.

  16. Recent research progress in pharmacological effects of glycyrrhizic acid%甘草酸药理作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    韩瑶聃; 王彬; 王政雨; 张亚弢; 杨凌云; 周金培; 张惠斌

    2012-01-01

    Glycyrrhizic acid, the main water-soluble constituent extracted from the roots of the Chinese herb Glycyrrhiza glabra, has been used for several thousands of year in traditional Chinese medicine. Both glycyrrhizic acid and its aglycone glycyrrhtic acid (GA) have been proven to be useful for various therapeutic purposes. Glycyrrhizic acid is used as a flavoring agent in some candies, pharmaceuticals, and tobacco products and is known for its anti-inflammatory, anti-ulcer, anti-allergic, anti-oxidant, immunomodulatory, anti-viral, anti-tumor and liver-protecting activities. In addition, glycyrrhizic acid has synergistic effect with other drugs. This paper reviewed the recent research progress in pharmacological effects of glycyrrhizic acid.%甘草的使用已有几千年历史,现在在世界各地广泛应用.甘草酸是中药甘草根部提取物中的重要成分之一,含有2分子葡萄糖醛酸和1分子甘草次酸,具有水溶性.甘草酸在临床上得到了广泛应用,甚至食品中也有使用.甘草酸有多种生物活性,例如抗炎、抗溃疡、抗过敏、抗氧化、免疫调节、抗病毒、抗癌和保肝等.此外与其他药物联用,甘草酸可起增效作用.本文综述了甘草酸的药理作用.

  17. Adsorption of Crystal violet on raw and acid-treated montmorillonite, K10, in aqueous suspension.

    Science.gov (United States)

    Sarma, Gautam Kumar; Sen Gupta, Susmita; Bhattacharyya, Krishna G

    2016-04-15

    Crystal violet is used as a dye in cotton and silk textiles, paints and printing ink. The dye is hazardous and exposure to it may cause permanent injury to the cornea and conjunctiva including permanent blindness, and in severe cases, may lead to respiratory and kidney failure. The present work describes removal of Crystal violet from aqueous solution by adsorption on raw and acid-treated montmorillonite, K10. The clay mineral was treated with 0.25 and 0.50 M sulfuric acid and the resulting materials were characterized by XRD, zeta potential, SEM, FTIR, cation exchange capacity, BET surface area and pore volume measurements. The influences of pH, interaction time, adsorbent amount, and temperature on adsorption were monitored and explained on the basis of physico-chemical characteristics of the materials. Basic pH generally favors adsorption but considerable removal was possible even under neutral conditions. Adsorption was very rapid and equilibrium could be attained in 180 min. The kinetics conformed to second order model. Langmuir monolayer adsorption capacity of raw montmorillonite K10 was 370.37 mg g(-1) whereas 0.25 M and 0.50 M acid treated montmorillonite K10 had capacities of 384.62 and 400.0 mg g(-1) respectively at 303 K. Adsorption was exothermic and decreased in the temperature range of 293-323 K. Thermodynamically, the process was spontaneous with Gibbs energy decreasing with rise in temperature. The results suggest that montmorillonite K10 and its acid treated forms would be suitable for removing Crystal violet from aqueous solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Effect of the application of acid treated biosolids on marigold (Tagetes erecta) development.

    Science.gov (United States)

    Díaz-Avelar, J; Barrios, J A; Jiménez, B

    2004-01-01

    The use of biosolids for land restoration and crop production is a potential solution to improve food production worldwide. However, the microbial content usually restricts its application in crops that are consumed uncooked. An alternative practice is their use in floriculture. In this study, the effects of acid treated sludge on the development of marigold (Tagetes erecta) plants were evaluated under green house conditions. Biosolids were applied at the agronomic rate (AR) based on nitrogen requirements of the marigold. In addition, higher rates (10 and 20xAR) were applied to study their effect on the plants. Biosolids were mixed with tepetate (hard volcanic indurate layers). Due to its origin, tepetate lacks nutrients and organic matter to adequately support plant development. The best treatment for marigold development was 10xAR, as plants reached an average height of 107 cm, with a growing speed of 1.01 cm/d, which is 20 times more than the control. Plants that received no biosolids produced 0.25 buds and 0.5 flowers per plant. In contrast, AR and 10xAR showed a production that ranged from 2 to 29 buds/plant and 4 to 15 flowers/plant, respectively. These results indicate the viability of reusing acid treated biosolids to improve marigold development.

  19. Differences in oxygen reduction catalysis of platinised acid treated Showa Denko carbon nanofibres

    DEFF Research Database (Denmark)

    Veltzé, Sune; Yli-Rantala, Elina; Borghei, Maryam;

    2011-01-01

    forms of the ECSA degradation: By agglomeration of the platinum crystallites, Rietveld ripening or indirectly by corrosion of the carbon support. Graphitised carbon nanostructures like carbon nanotubes (CNTs), carbon nanofibres (CNFs), etc. are proposed as carbon support substitutes to avoid carbon......The use of carbon as support material for platinum nano-crystallites in polymer electrolyte fuel cells (PEFC) is a common method for increasing the electrochemical specific surface area (ECSA) of platinum. During fuel cell operation, the conditions that catalysts are subjected to lead to various...... corrosion, as the nanostructures are thermally and chemically more durable. The presented work describes the effects on surface defect of acid treated Showa Denko vapour grown carbon fibres (VGCF®/VGCF-H®). A selection of carbon fibres have been platinised and the differences of the oxygen reduction...

  20. Adsorption of Pb(II Ions on Sulfuric Acid Treated Leucaena leucocephala Leaf Powder

    Directory of Open Access Journals (Sweden)

    Mansur Noor Fhadzilah

    2015-01-01

    Full Text Available Sulfuric acid treated Petai belalang (Leucaena leucocephala leaf powder (SLLP was used as an adsorbent for Pb(II ions removal. The experimental adsorption parameters investigated include pH, dosage and initial Pb(II concentration. Pb(II removal was more favored at a higher adsorbent dosage, pH and temperature. Adsorption kinetics conformed to the pseudo-second order model while Langmuir isotherm model recorded the value of maximum adsorption capacity (qmax of 222 mg/g. The major functional groups involved in the adsorption process were identified as hydroxyl, amino and ether as revealed by the FTIR analysis. The prepared adsorbent demonstrated a potential application for efficient removal of Pb(II ions from industrial wastewater.

  1. Enhanced high temperature thermoelectric response of sulphuric acid treated conducting polymer thin films

    KAUST Repository

    Sarath Kumar, S. R.

    2015-11-24

    We report the high temperature thermoelectric properties of solution processed pristine and sulphuric acid treated poly(3, 4-ethylenedioxythiophene):poly(4-styrenesulfonate) (or PEDOT:PSS) films. The acid treatment is shown to simultaneously enhance the electrical conductivity and Seebeck coefficient of the metal-like films, resulting in a five-fold increase in thermoelectric power factor (0.052 W/m. K ) at 460 K, compared to the pristine film. By using atomic force micrographs, Raman and impedance spectra and using a series heterogeneous model for electrical conductivity, we demonstrate that acid treatment results in the removal of PSS from the films, leading to the quenching of accumulated charge-induced energy barriers that prevent hopping conduction. The continuous removal of PSS with duration of acid treatment also alters the local band structure of PEDOT:PSS, resulting in simultaneous enhancement in Seebeck coefficient.

  2. Adsorption of chloridazon from aqueous solution on heat and acid treated sepiolites.

    Science.gov (United States)

    González-Pradas, E; Socías-Viciana, M; Ureña-Amate, M D; Cantos-Molina, A; Villafranca-Sánchez, M

    2005-05-01

    The adsorption of chloridazon on heat treated sepiolite samples at 110 degrees C (S-110), 200 degrees C (S-200), 400 degrees C (S-400), 600 degrees C (S-600) and acid treated samples with H2SO4 solutions of two different concentrations (0.25 and 1.0M) (S-0.25 and S-1.0, respectively) from pure water at 25 degrees C has been studied by using batch experiments. In addition, column experiments were carried out with the natural (S-110) and 600 degrees C (S-600) heat treated samples, using a 10.30 mg l-1 aqueous solution of chloridazon. The adsorption experimental data points have been fitted to the Freundlich equation in order to calculate the adsorption capacities (Kf) of the samples; Kf values range from 2.89 mg kg-1 for the S-1.0 sample up to 164 mg kg-1 for the S-600 sample; so, the heat treatment given to the sepiolite greatly increases its adsorption capacity for the herbicide chloridazon whereas the acid treatment produces a clear decrease in the amount of chloridazon adsorbed. The removal efficiency (R) has also been calculated; R values ranging from 5.08% for S-1.0 up to 60.9% for S-600. The batch experiments showed that the strongest heat treatment is more effective than the natural and acid treated sepiolite in relation to adsorption of chloridazon. The column experiments also showed that 600 degrees C heat treated sepiolite might be reasonably used in removing chloridazon from water. Thus, as this type of clay is relatively plentiful, these activated samples might be reasonably used in order to remove chloridazon from water.

  3. Nitric Acid-Treated Carbon Fibers with Enhanced Hydrophilicity for Candida tropicalis Immobilization in Xylitol Fermentation

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    Le Wang

    2016-03-01

    Full Text Available Nitric acid (HNO3-treated carbon fiber (CF rich in hydrophilic groups was applied as a cell-immobilized carrier for xylitol fermentation. Using scanning electron microscopy, we characterized the morphology of the HNO3-treated CF. Additionally, we evaluated the immobilized efficiency (IE of Candida tropicalis and xylitol fermentation yield by investigating the surface properties of nitric acid treated CF, specifically, the acidic group content, zero charge point, degree of moisture and contact angle. We found that adhesion is the major mechanism for cell immobilization and that it is greatly affected by the hydrophilic–hydrophilic surface properties. In our experiments, we found 3 hto be the optimal time for treating CF with nitric acid, resulting in an improved IE of Candida tropicalis of 0.98 g∙g−1 and the highest xylitol yield and volumetric productivity (70.13% and 1.22 g∙L−1∙h−1, respectively. The HNO3-treated CF represents a promising method for preparing biocompatible biocarriers for multi-batch fermentation.

  4. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    Science.gov (United States)

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

  5. Removal of Pb(II) ions from aqueous solutions by sulphuric acid-treated wheat bran.

    Science.gov (United States)

    Ozer, A

    2007-03-22

    Sulphuric acid-treated wheat bran (STWB) was used as an adsorbent to remove Pb(II) ions from aqueous solution. It was observed that the adsorption yield of Pb(II) ions was found to be pH dependent. The equilibrium time for the process was determined as 2h. STWB gave the highest adsorption yield at around pH 6.0. At this pH, adsorption percentage for an initial Pb(II) ions concentration of 100mg/L was found to be 82.8 at 25 degrees C for contact time of 2h. The equilibrium data obtained at different temperatures fitted to the non-linear form of Langmuir, Freundlich and Redlich-Peterson and linear form of Langmuir and Freundlich models. Isotherm constants were calculated and compared for the models used. The maximum adsorption capacity (q(max)) which was obtained linear form of Langmuir model increased from 55.56 to 79.37mg/g with increasing temperature from 25 to 60 degrees C. Similar trend was observed for other isotherm constants related to the adsorption capacity. Linear form of Langmuir isotherm data was evaluated to determine the thermodynamic parameters for the process. Thermodynamic parameters show that adsorption process of Pb(II) ions is an endothermic and more effective process at high temperatures. The pseudo nth order kinetic model was successfully applied to the kinetic data and the order (n) of adsorption reaction was calculated at the range from 1.711 to 1.929. The values of k(ad) were found to be 5.82x10(-4) and 21.81x10(-4)(min(-1))(mg/g)(1-n) at 25 and 60 degrees C, respectively. Activation energy was determined as 29.65kJ/mol for the process. This suggest that the adsorption Pb(II) ions by STWB is chemically controlled.

  6. Cloning and characterization of the gene encoding β-amyrin synthase in the glycyrrhizic acid biosynthetic pathway in Glycyrrhiza uralensis

    Directory of Open Access Journals (Sweden)

    Honghao Chen

    2013-12-01

    Full Text Available Glycyrrhiza uralensis is considered to be one of the most important herbs in traditional Chinese medicine due to its numerous pharmacological effects particularly its ability to relieve cough and act as a mucolytic. Based on previous research, these effects are mediated by a number of active ingredients, especially glycyrrhizic acid (GA. In the present study, a gene encoding β-amyrin synthase (β-AS involved in GA biosynthesis in G. uralensis has been cloned and expressed in Saccharomyces cerevisiae. The cloned enzyme showed similar activity to native enzymes isolated from other Glycyrrhiza species to catalyze the conversion of 2,3-oxidosqualene into β-amyrin. In fact the β-AS gene is particularly important in the GA biosynthetic pathway in G. uralensis. The complete sequence of the enzyme was determined and a phylogenetic tree based on the β-AS gene of G. uralensis and 20 other species was created. This showed that Glycyrrhiza glabra had the closest kinship with G. uralensis. The results of this work will be useful in determining how to improve the efficacy of G. uralensis by improving its GA content and in exploring the biosynthesis of GA in vitro.

  7. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  8. The effects of glycyrrhizic acid and glabridin in the regulation of CXCL5 inflammation gene on acceleration of wound healing

    Institute of Scientific and Technical Information of China (English)

    Hong Yung Yip; Melissa Su Wei Poh; Yoke Yin Chia

    2016-01-01

    Objective: To evaluate the anti-inflammatory property of both glycyrrhizic acid(GA)and glabridin in reducing inflammation to accelerate wound regeneration on 3T3-L1 and NIH-3T3 fibroblast cell lines.Methods: Cell proliferation and viability assay(MTT assay), scratch wound healing assays,and quantitative real-time PCR were conducted to investigate the effects on cell proliferation,cell migration, and expression of CXC chemokine ligand 5 inflammation gene respectively.Results: Results showed that at a low concentration of 1 × 10-8mol/L, glabridin down regulated cell proliferation in NIH-3T3 significantly, suggesting its involvement in ERK1/2 signaling pathway. GA and glabridin significantly accelerated cell migration through wound healing in both 3T3-L1 and NIH-3T3 and significantly down regulated the expression of CXC chemokine ligand 5 in 3T3-L1 at concentration 1 × 10-8mol/L,indicating the possible involvement of nuclear factor-k B and cyclooxygenase 2 transcriptions modulation.Conclusions: Both GA and glabridin can serve as potential treatment for chronic inflammatory disease, and glabridin as an oncogenic inhibitor due to its anti-proliferative property.

  9. Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in human dermal fibroblasts.

    Science.gov (United States)

    Afnan, Quadri; Adil, Mushtaq Dar; Nissar-Ul, Ashraf; Rafiq, Ahmad Rather; Amir, Hussian Faridi; Kaiser, Peerzada; Gupta, Vijay Kumar; Vishwakarma, Ram; Tasduq, Sheikh Abdullah

    2012-05-15

    Glycyrrhizic acid (GA), a triterpenoid saponin glycoside from the roots and rhizomes of licorice is used in traditional and modern medicine for the treatment of numerous medical conditions including skin diseases and beauty care product. In the present study, we investigated the effect of GA against ultraviolet B (UVB) irradiation-induced photoaging in human dermal fibroblasts (HDFs) and its possible mechanism of action. HDFs were subjected to photoaging by sub-toxic dose of UVB (10 mj/cm(2)) irradiation. Cell viability, matrix metalloproteinase 1 (MMP1), pro-collagen 1, cellular and nuclear morphology, cell cycle, intracellular reactive oxygen species (ROS), caspase 3 and hyaluronidase inhibition assays were performed. Western blotting was used to evaluate the expression of NF-kappa B (NF-κB) and cytochrome-C proteins. GA treatment significantly inhibited photoaging. It achieved this by reducing ROS, NF-κB, cytochrome c, caspase 3 levels and inhibiting hyaluronidase enzyme. The main mechanism seems to be, most likely by blocking MMP1 activation by modulating NF-κB signaling. These findings may be useful for development of natural and safe photoprotective agents against UVB irradiation. Copyright © 2012 Elsevier GmbH. All rights reserved.

  10. Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

    Science.gov (United States)

    Kim, Ji-Sun; Cheon, Soyoung; Kim, Seung Woo; Kim, Boram; Kim, Heejaung; Park, Ki Duk; Kim, Sung-Min

    2016-09-16

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. SELF-CLEANING GLASS BASED ON ACID-TREATED TiO2 FILMS WITH PALMITIC ACID AS MODEL POLLUTANT

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    Nurul Hidayat Aprilita

    2010-06-01

    Full Text Available Preparation and characterization of self-cleaning glass based on acid-treated TiO2 films as well as evaluation on their self-cleaning properties have been carried out. Palmitic acid photodegradation was used as model pollutant. Acid-treated TiO2 powders were deposited on glass surface by using spraying technique. The XRD results showed that acid-treated TiO2 film exhibited decreased anatase crystalline size. The corresponding SEM images showed porous surface morphology. Layer densification was observed as the film thickness increased. TiO2 photocatalytic activity increased as the length of UV radiation increased. Best results were obtained at experimental condition of 35 hours UV radiation time. It is also observed that the thickness of TiO2 layers influenced the efficiency of palmitic acid photodegradation. The film with 1.661 µm thick TiO2 layers and 6.933 mg weight (0.7164 mg/cm2 could degrade 97.54 % mg palmitic acid/cm2 thin film.   Keywords: TiO2 films, acid treatment, self-cleaning glass

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

    Science.gov (United States)

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

    2012-08-01

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

  13. Isolation of an Glycyrrhizic Acid-producing Andophytic Fungus from Licorice and Analysis of Metabolites%一株产甘草酸内生真菌的分离及代谢产物分析

    Institute of Scientific and Technical Information of China (English)

    王红霞; 李雅丽

    2011-01-01

    采用组织块法从采自内蒙古鄂尔多斯市的甘草根部分离纯化内生真菌,经液体发酵培养,抽提发酵粗产物,以甘草酸为标准品采用LC-MS法和HPLC法对这些真菌的代谢产物进行筛选,获得1株产甘草酸的内生菌,通过形态学研究初步确定该菌株为镰孢霉属.%A strain of glycyrrhizic acid-producing endophytic fungi was obtained from the rats of licorice in Erdos city of the Inner Mongolia autonomous region by tissue culture method. Then the purified endophytic fungal strains were fermented. The glycyrrhizic acid in the fungal extract was extract and confirmed by HPLC and LC-MS by comparison with glycyrrhizic acid standard. The strain B12 that was found as the glycyrrhizic acid-producing andophytic fungus was grouped into Fusarium based on the morphological traits.

  14. UPLC-MS/MS determination of ephedrine, methylephedrine, amygdalin and glycyrrhizic acid in Beagle plasma and its application to a pharmacokinetic study after oral administration of Ma Huang Tang.

    Science.gov (United States)

    Yan, Tianhua; Fu, Qiang; Wang, Jing; Ma, Shiping

    2015-02-01

    An ultra performance liquid chromatography-mass spectrometric (UPLC-MS) method was developed to investigate the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of Ma Huang Tang (MHT) in Beagles. Beagle plasma samples were pretreated using liquid-liquid extraction, and chromatographic separation was performed on a C18 column using a linear gradient of water-formic acid mixture (0.1%). The pharmacokinetic parameters of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid from MHT in Beagles were quantitatively determined by UPLC with tandem mass detector. The qualitative detection of the four compounds was accomplished by selected ion monitoring in negative/positive ion modes electrospray ionization-mass spectrometry (ESI-MS). Detection was based on multiple reaction monitoring with the precursor-to-product ion transitions m/z 166.096-116.983 (ephedrine), m/z 179.034-146.087 (methylephedrine), m/z 456.351-323.074 (amygdalin), and m/z 821.606-351.062 (glycyrrhizic acid). The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression, and stability were within the acceptable ranges. The method described was successfully applied to reveal the pharmacokinetic properties of ephedrine, methylephedrine, amygdalin, and glycyrrhizic acid after oral gavage of MHT in Beagles. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Glycyrrhetic acid, but not glycyrrhizic acid, strengthened entecavir activity by promoting its subcellular distribution in the liver via efflux inhibition.

    Science.gov (United States)

    Chen, Qianying; Chen, Hongzhu; Wang, Wenjie; Liu, Jiali; Liu, Wenyue; Ni, Ping; Sang, Guowei; Wang, Guangji; Zhou, Fang; Zhang, Jingwei

    2017-08-30

    Entecavir (ETV) is a superior nucleoside analogue used to treat hepatitis B virus (HBV) infection. Although its advantages over other agents include low viral resistance and the elicitation of a sharp decrease in HBV DNA, adverse effects such as hepatic steatosis, hepatic damage and lactic acidosis have also been reported. Glycyrrhizin has long been used as hepato-protective medicine. The clinical combination of ETV plus glycyrrhizin in China displays better therapeutic effects and lower rates of liver damage. However, there is little evidence explaining the probable synergistic mechanism that exists between these two drugs from a pharmacokinetics view. Here, alterations in the plasma pharmacokinetics, tissue distribution, subcellular distribution, and in vitro and in vivo antiviral activity of ETV after combination with glycyrrhizic acid (GL) were analysed to determine the synergistic mechanisms of these two drugs. Specific efflux transporter membrane vesicles were also used to elucidate their interactions. The primary active GL metabolite, glycyrrhetic acid (GA), did not affect the plasma pharmacokinetics of ETV but promoted its accumulation in hepatocytes, increasing its distribution in the cytoplasm and nucleus and augmenting the antiviral efficiency of ETV. These synergistic actions were primarily due to the inhibitory effect of GA on MRP4 and BCRP, which transport ETV out of hepatocytes. In conclusion, GA interacted with ETV at cellular and subcellular levels in the liver through MRP4 and BCRP inhibition, which enhanced the antiviral activity of ETV. Our results partially explain the synergistic mechanism of ETV and GL from a pharmacokinetics view, providing more data to support the use of these compounds together in clinical HBV treatment. Copyright © 2017. Published by Elsevier B.V.

  16. Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: structure-activity relationships.

    Science.gov (United States)

    Lin, Jung-Chung; Cherng, Jaw-Ming; Hung, Man-Shan; Baltina, Lidia A; Baltina, Lia; Kondratenko, Rimma

    2008-07-01

    Glycyrrhizic acid (18beta-GL or GL) is a herbal drug with a broad spectrum of antiviral activities and pharmacological effects and multiple sites of action. Previously we showed that GL inhibits Epstein-Barr virus (EBV) infection in vitro by interfering with an early step of the EBV replication cycle (possibly attachment/penetration). Here we tested the effects of 15 GL derivatives against EBV infection by scoring the numbers of cell expressing viral antigens and quantifying EBV DNA copy numbers in superinfected Raji cells. The derivatives were made either by transformation of GL on carboxyl and hydroxyl groups or by conjugation of amino acid residues into the carbohydrate part. We identified seven compounds active against EBV and all showed dose-dependent inhibition as determined by both assays. Among these active compounds, the introduction of amino acid residues into the GL carbohydrate part enhanced the antiviral activity in three of the seven active compounds. However, when Glu(OH)-OMe was substituted by Glu(OMe)-OMe, its antiviral activity was completely abolished. Introduction of potassium or ammonium salt to GL reduced the antiviral activity with no significant effect on cytotoxicity. The alpha-isomer (18alpha-GL) of 18beta-GL was as potent as the beta-form, but its sodium salt lost antiviral activity. The metabolic product of GL, 18beta-glycyrrhetinic acid (18beta-GA or GA), was 7.5-fold more active against EBV than its parental compound GL but, concomitantly, exhibited increased cytotoxicity resulting in a decreased therapeutic index.

  17. Modulation expression of tumor necrosis factor α in the radiation-induced lung injury by glycyrrhizic acid

    Directory of Open Access Journals (Sweden)

    Soheila Refahi

    2015-01-01

    Full Text Available To evaluate the ability of glycyrrhizic acid (GLA to reduce the tumor necrosis factor α (TNF-α, release on messenger ribonucleic acid (mRNA and protein production in the lungs using GLA in response to irradiation were studied. The animals were divided into four groups: No treatment (NT group, GLA treatment only (GLA group, irradiation only (XRT group, and GLA treatment plus irradiation (GLA/XRT group. Rats were killed at different time points. Real-time reverse transcriptase polymerase chain reaction (RT-PCR was used to evaluate the mRNA expression of TNF-α in the lungs (compared with non-irradiated lungs. An enzyme-linked immunosorbant assay (ELISA assay was used to measure the TNF-α protein level. The TNF-α mRNA expression in the lungs of the XRT rats was clearly higher at all-time points compared to the NT rats. The TNF-α mRNA expression in the lungs of the GLA/XRT rats was lower at all-time points compared to the XRT rats. Release of the TNF-α on protein level in the lungs of the XRT rats increased at all-time points compared to the NT rats. In contrast to the XRT rats, the lungs of the GLA/XRT rats revealed a reduction on TNF-α protein level at 6 h after irradiation. This study has clearly showed the immediate down-regulation of the TNF-α mRNA and protein production in the lungs using GLA in response to irradiation.

  18. Biosorption of hexavalent chromium by raw and acid-treated green alga Oedogonium hatei from aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, V.K. [Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667 (India)], E-mail: vinodfcy@iitr.ernet.in; Rastogi, A. [Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667 (India)

    2009-04-15

    The hexavalent chromium, Cr(VI), biosorption by raw and acid-treated Oedogonium hatei were studied from aqueous solutions. Batch experiments were conducted to determine the biosorption properties of the biomass. The optimum conditions of biosorption were found to be: a biomass dose of 0.8 g/L, contact time of 110 min, pH and temperature 2.0 and 318 K respectively. Both Langmuir and Freundlich isotherm equations could fit the equilibrium data. Under the optimal conditions, the biosorption capacities of the raw and acid-treated algae were 31 and 35.2 mg Cr(VI) per g of dry adsorbent, respectively. Thermodynamic parameters showed that the adsorption of Cr(VI) onto algal biomass was feasible, spontaneous and endothermic under studied conditions. The pseudo-first-order kinetic model adequately describe the kinetic data in comparison to second-order model and the process involving rate-controlling step is much complex involving both boundary layer and intra-particle diffusion processes. The physical and chemical properties of the biosorbent were determined and the nature of biomass-metal ions interactions were evaluated by FTIR analysis, which showed the participation of -COOH, -OH and -NH{sub 2} groups in the biosorption process. Biosorbents could be regenerated using 0.1 M NaOH solution, with up to 75% recovery. Thus, the biomass used in this work proved to be effective materials for the treatment of chromium bearing aqueous solutions.

  19. Biosorption of hexavalent chromium by raw and acid-treated green alga Oedogonium hatei from aqueous solutions.

    Science.gov (United States)

    Gupta, V K; Rastogi, A

    2009-04-15

    The hexavalent chromium, Cr(VI), biosorption by raw and acid-treated Oedogonium hatei were studied from aqueous solutions. Batch experiments were conducted to determine the biosorption properties of the biomass. The optimum conditions of biosorption were found to be: a biomass dose of 0.8 g/L, contact time of 110 min, pH and temperature 2.0 and 318 K respectively. Both Langmuir and Freundlich isotherm equations could fit the equilibrium data. Under the optimal conditions, the biosorption capacities of the raw and acid-treated algae were 31 and 35.2 mg Cr(VI) per g of dry adsorbent, respectively. Thermodynamic parameters showed that the adsorption of Cr(VI) onto algal biomass was feasible, spontaneous and endothermic under studied conditions. The pseudo-first-order kinetic model adequately describe the kinetic data in comparison to second-order model and the process involving rate-controlling step is much complex involving both boundary layer and intra-particle diffusion processes. The physical and chemical properties of the biosorbent were determined and the nature of biomass-metal ions interactions were evaluated by FTIR analysis, which showed the participation of -COOH, -OH and -NH(2) groups in the biosorption process. Biosorbents could be regenerated using 0.1 M NaOH solution, with up to 75% recovery. Thus, the biomass used in this work proved to be effective materials for the treatment of chromium bearing aqueous solutions.

  20. 大孔吸附树脂纯化甘草提取物中甘草酸的研究%Macroporous Adsorption Resin Purification of Glycyrrhizic Acid in Glycyrrhiza Extract Research

    Institute of Scientific and Technical Information of China (English)

    丁利营; 李红艳

    2014-01-01

    Objective To study the best macroporous resin purification process for Glycyrrhizic acid from glycyrrhiza glabra. Methods Glycyrrhizic acid content in macroporous resin purification as the investigation index, select the best macroporous resin from 24 kinds of macroporous resins for Glycyrrhizic acid from liquorice extract, and determine the optimum process conditions for this purification. Results AB-8 macroporous adsorption resin has the best purification ef ect for glycyrrhizic acid, and the optimum process conditions:liquorice extract concentration is 0.11mg/ml, diameter/height is 1:8, liquorice extract volume is 2 times of the resin, the rates of using liquorice extract and elution both are 2bv/h, remove impurities with 30%&50%ETOH, and accumulate glycyrrhizic acid by using 80%ETOH. After purification, the purity of the product is 60.74%, the yield rate is 3.29%, the transfer rate is 76.72%. Conclusion Using AB-8 macroporous adsorption resin can purify glycyrrhizic acid very wel .%目的研究光果甘草中甘草酸的最佳大孔树脂纯化工艺。方法以大孔吸附树脂纯化物中甘草酸的含量为考察指标,从24种大孔吸附树脂中筛选出纯化甘草粗提物中甘草酸的最佳大孔吸附树脂,并确定纯化甘草酸的最佳工艺条件。结果 AB-8大孔吸附树脂纯化甘草酸效果最佳,最佳工艺条件院上柱液浓度为0.11mg/mL,径高比为1:8,上样体积为所用树脂2BV,上样速度与洗脱速度均为2BV/h,用30%、50%的乙醇除杂,用80%乙醇富集甘草酸。纯化后产品纯度为60.74%,收率为3.29%,转移率为76.33%。结论采用AB-8大孔吸附树脂可较好地纯化甘草酸。

  1. Esterification of levulinic acid to n-butyl levulinate over heteropolyacid supported on acid-treated clay

    Institute of Scientific and Technical Information of China (English)

    S.Dharne; V.V.Bokade

    2011-01-01

    Levulinic acid has been identified as a promising green, biomass-derived platform chemical, n-Butyl levulinate is used as an important intermediate having diverse applications.The present work focuses on the synthesis of n-butyl levulinate by esterification of levulinic acid with n-butanol using heteropolyacid (HPA) supported on acid-treated clay montmorillonite (K10).20% (w/w) dodecatungestophosphoric acid (DTPA) supported on K10 was found to be the most efficient catalyst with 97% levulinic acid conversion and 100% selectivity towards n-butyl levulinate.Effects of various process parameters were studied to examine the efficacy of 20% (w/w) DTPA/K10 for optimization of the activity.

  2. Thorium(IV) removal from aqueous medium by citric acid treated mangrove endophytic fungus Fusarium sp. #ZZF51.

    Science.gov (United States)

    Yang, S K; Tan, N; Yan, X M; Chen, F; Long, W; Lin, Y C

    2013-09-15

    Thorium(IV) biosorption is investigated by citric acid treated mangrove endophytic fungus Fussarium sp. #ZZF51 (CA-ZZF51) from South China Sea. The biosorption process was optimized at pH 4.5, equilibrium time 90 min, initial thorium(IV) concentration 50 mg L(-1) and adsorbent dose 0.6 g L(-1) with 90.87% of removal efficiency and 75.47 mg g(-1) of adsorption capacity, which is obviously greater than that (11.35 mg g(-1)) of the untreated fungus Fussarium sp. #ZZF51 for thorium(IV) biosorption under the condition of optimization. The experimental data are analyzed by using isotherm and kinetic models. Kinetic data follow the pseudo-second-order model and equilibrium data agree very well with the Langmuir model. In addition, FTIR analysis indicates that hydroxyl, amino, and carbonyl groups act as the important roles in the adsorption process.

  3. A comparison of orally administered misoprostol and membrane ...

    African Journals Online (AJOL)

    Post-term pregnancy is fairly common in obstetric practice and is the most ... MS involves digital separation of the fetal membranes from the lower ... term.10,11 This method causes an increase in local PG production,12,13 which results in ...

  4. Therapeutic effect of orally administered microencapsulated oxaliplatin for colorectal cancer.

    Science.gov (United States)

    Urbanska, Aleksandra M; Karagiannis, Emmanouil D; Guajardo, Gonzalo; Langer, Robert S; Anderson, Daniel G

    2012-06-01

    Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality.

  5. Absorption and distribution of orally administered jojoba wax in mice.

    Science.gov (United States)

    Yaron, A; Samoiloff, V; Benzioni, A

    1982-03-01

    The liquid wax obtained from the seeds of the arid-land shrub jojoba (Simmondsia chinensis) is finding increasing use in skin treatment preparations. The fate of this wax upon reaching the digestive tract was studied. 14C-Labeled wax was administered intragastrically to mice, and the distribution of the label in the body was determined as a function of time. Most of the wax was excreted, but a small amount was absorbed, as was indicated by the distribution of label in the internal organs and the epididymal fat. The label was incorporated into the body lipids and was found to diminish with time.

  6. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  7. Biodegradable Bioadherent Microcapsules for Orally Administered Sustained Release Vaccines

    Science.gov (United States)

    1997-05-01

    Fasciola hepatica which is a known bioadhesive’’. The encapsulation method is the classical, well described water in oil technique for the preparation of...immunization, Vaccine 12 (1994) 387-340. 6. Waite, J.H., Rice-Ficht, A.C., Presclerotized eggshell protein from the liver fluke Fasciola hepatica ...Biochemistry 26 (1987) 7819-7825. 7. Waite, J.H., Rice-Ficht, A.C., Eggshell precursor proteins of Fasciola hepatica : II. Microheterogeneity in vitelline

  8. Penetration of orally administered prulifloxacin into human prostate tissue.

    Science.gov (United States)

    Giberti, Claudio; Gallo, Fabrizio; Rosignoli, Maria T; Ruggieri, Alessandro; Barattè, Simona; Picollo, Rossella; Dionisio, Paolo

    2009-01-01

    Prulifloxacin, a fluoroquinolone antibacterial agent, may be a useful addition to the antimicrobial armamentarium against prostatitis once the ability of its active metabolite, ulifloxacin, to penetrate prostatic tissue has been determined. This study set out to evaluate ulifloxacin penetration into the prostate following administration of the oral fluoroquinolone prodrug prulifloxacin in patients undergoing transurethral resection of the prostate (TURP). This was a phase I, randomized, open-label, single-centre study involving 20 male Caucasian patients (mean age 63.1 years) requiring TURP for treatment of benign prostatic hyperplasia. Sixteen patients were randomized to receive prulifloxacin; the other four patients were not treated (controls) in order to validate the bioanalytical method. Patients in the active treatment groups were randomized to receive one or three once-daily doses of prulifloxacin 600 mg, with the last administration 3 hours prior to surgery. Central/transitional and peripheral zone prostatic tissue samples were obtained from the 6 o'clock and 9 o'clock positions in the prostate, and blood samples were collected concurrently. Ulifloxacin concentrations were determined in the tissue samples and plasma using liquid chromatography-tandem mass spectrometry. Safety was also assessed. Prostatic tissue concentrations of ulifloxacin always exceeded those in plasma. Mean ulifloxacin concentrations measured in samples collected from the 6 o'clock central/transitional zone of the prostate were higher in patients who received prulifloxacin for 3 days than in those who received a single dose. Mean prostatic tissue/plasma ulifloxacin concentration ratios after single and repeated prulifloxacin administration ranged from 3.8 to 7.1 and from 3.9 to 9.5, respectively. The highest mean ratio was found in the 6 o'clock central/transitional zone after repeated dosing. Prostatic levels of ulifloxacin were above the minimum inhibitory concentrations for the most common causative pathogens of bacterial prostatitis. No treatment-related toxicities were reported. These findings confirm the ability of prulifloxacin to penetrate prostatic tissues, indicating high exposure of the target tissue to ulifloxacin and, therefore, a potential therapeutic role for prulifloxacin in the treatment of bacterial prostatic infections.

  9. Antinociceptive effects of Cremophor EL orally administered to mice

    Directory of Open Access Journals (Sweden)

    Z. Tabarelli

    2003-01-01

    Full Text Available Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight or saline (0.9% NaCl, 10 ml/kg body weight. CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL.

  10. 复方甘草酸苷片联合米诺地尔溶液治疗斑秃疗效观察%Compound glycyrrhizic acid joint of minoxidil topical solution treatment bald spot observe clinical curative effect

    Institute of Scientific and Technical Information of China (English)

    俞莺; 袁波

    2012-01-01

    Objective To observe the compound glycyrrhizic acid joint of minoxidil with those minoxidil treatment bald spot curative effect controls. Methods 104 patients were randomly divided into the bald spot with the control group, the control group use minoxidil, based on the experimental group in the control group add compound glycyrrhizic acid piece of treatment. Results the recovery rate and efficient were significantly higher than those in control group (P< 0.01). Conclusion Compound glycyrrhizic acid treatment bald spot effective and safe.%目的:观察复方甘草酸苷片联合米诺地尔与单用米诺地尔治疗斑秃的疗效.方法:将104例斑秃患者随机分为治疗组与对照组:对照组单用米诺地尔,治疗组在对照组基础上加用复方甘草酸苷片治疗.结果:治疗组痊愈率与有效率均显著高于对照组(P<0.01).结论:复方甘草酸苷片联合米诺地尔治疗斑秃安全、有效,可推广应用.

  11. Two Step Enzymatic Hydrolysis and Fermentation Strategy for Conversion of Acid Treated Hydrolysate of Corn Cob to Ethanol

    Directory of Open Access Journals (Sweden)

    *Geetanjali Swaroop Wakade

    2015-03-01

    Full Text Available For economic production of ethanol from corncobs, it is very crucial that lignocellulosic fractions containing glucose and xylose are simultaneously fermented to ethanol in a single operation i.e. cofermentation. Cofermentation of mixed acid treated corn cob hydrolysate containing mixed sugars at low concentration (<50 g L -1 using Pichia stipitis showed 92.35% ethanol fermentation efficiency. However cofermentation of corn cob hydrolysate comprising sugar above 50 g L-1 showed only 46.71% ethanol fermentation efficiency. Therefore a two step enzymatic hydrolysis and fermentation strategy was designed for cofermentation of corn cob hydrolysate containing high concentration of sugars which resulted in 86.74% enzymatic hydrolysis efficiency and 75.32% ethanol fermentation efficiency. Using two step hydrolysis and fermentation, there was 1.1 fold improvement in the enzymatic hydrolysis efficiency. Final ethanol concentration, ethanol yield and volumetric productivity were improved by 1.7, 1.66 and 2.6 fold respectively as compared to single step hydrolysis and fermentation process.

  12. Carbon Dioxide Sorption Isotherm Study on Pristine and Acid-Treated Olivine and Its Application in the Vacuum Swing Adsorption Process

    Directory of Open Access Journals (Sweden)

    Jiajie Li

    2015-05-01

    Full Text Available This paper investigates the potential of pristine and acid-treated olivine as a substrate for CO2 capture using a vacuum swing adsorption (VSA process from the gas-solid phase. The experiments tested the isotherm of pure CO2 adsorption with partial pressure from 10−5 to 1 bar at ambient temperature. The CO2 adsorption capacity and actual expected working capacity (EWC curves of pristine and acid-treated olivine were determined. Isotherm studies predict that physisorption dominates chemisorptions at ambient temperatures. The adsorption capacity enhances with the increase of specific surface area, pore volume, and the appearance of Mg complexed on the mineral’s surface. Actual EWC studies showed that acid-treated olivine is an adsorbent choice for the VSA process, due to enhanced CO2 adsorption capacities compared to olivine and the potential for 100% recovery of CO2 during the regeneration process. Pristine olivine is not suitable for the VSA process because of bad regenerability, but it can be used in capturing and sequestering dilute CO2 in process streams. Our research reveals excellent viability for the application of VSA in the area of CO2 capture using pristine olivine and acid-treated olivine.

  13. Effects of temperature on adsorption and oxidative degradation of bisphenol A in an acid-treated iron-amended granular activated carbon

    Science.gov (United States)

    The present study suggests a combined adsorption and Fenton oxidation using an acid treated Fe-amended granular activated carbon (Fe-GAC) for effective removal of bisphenol A in water. When the Fe-GAC adsorbs and is saturated with BPA in water, Fenton oxidation of BPA occurs in ...

  14. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Eu Chia

    2010-07-01

    Full Text Available Abstract Background The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL, an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR. Glycyrrhizic acid (GA, a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state. Results Oral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR (p Conclusion In conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

  15. ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, D. [School of Life Sciences, Jilin University, Changchun (China); The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun (China); Guo, T.Q. [School of Life Sciences, Jilin University, Changchun (China); Wang, Z.Y. [State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun (China); Lu, J.H.; Liu, D.P.; Meng, Q.F.; Xie, J. [School of Life Sciences, Jilin University, Changchun (China); Zhang, X.L. [Faculty of ScienceNational University of Singapore (Singapore); Liu, Y. [School of Life Sciences, Jilin University, Changchun (China); Teng, L.S. [School of Life Sciences, Jilin University, Changchun (China); The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun (China)

    2014-07-25

    The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

  16. Glycyrrhizic Acid Can Attenuate Metabolic Deviations Caused by a High-Sucrose Diet without Causing Water Retention in Male Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hamish Alexander Fernando

    2014-11-01

    Full Text Available Glycyrrhizic acid (GA ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2. We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.

  17. Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ, Lipoprotein Lipase (LPL, Serum Lipid and HOMA-IR in Rats

    Directory of Open Access Journals (Sweden)

    Chia Yoke Yin

    2010-01-01

    Full Text Available Studies on ligand binding potential of glycyrrhizic acid, a potential agonist to PPARγ, displayed encouraging results in amelioration of metabolic syndrome. The regulation of gene cassettes by PPARγ affects glucose homeostasis, lipid, lipoprotein metabolism and adipogenesis. This study was performed to determine the effects of GA on total PPARγ and LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARγ and LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles. Thus, oral administration of 100 mg/kg GA for 24 hours improved insulin sensitivity and lipid profiles and induced upregulation of total PPARγ and LPL expression levels in all studied tissues.

  18. Preparation of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles for hepatocellular carcinoma-targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Zu Y

    2013-03-01

    Full Text Available Yuangang Zu, Li Meng, Xiuhua Zhao, Yunlong Ge, Xinyang Yu, Yin Zhang, Yiping Deng Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, People’s Republic of China Introduction: The livertaxis of glycyrrhizic acid-conjugated bovine serum albumin (GL-BSA has been reported in the literature. Now, in this paper, we describe a novel type of drug-targeted delivery system containing 10-hydroxycamptothecin (HCPT with liver tumor targeting. Methods: First, GL was coupled to BSA then HCPT was encapsulated in GL-BSA by high-pressure homogenization emulsification. In the experimental design, the influencing variables on particle size and drug loading efficiency were determined to be BSA concentration, volume ratio of water to organic phase, and speed and speed duration of homogenization as well as homogenization pressure and the number of times homogenized at certain pressures. Particle size plays an important role in screening optimal conditions of nanoparticles preparation. Characteristics of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles (GL-BSA-HCPT-NPs, such as the drug encapsulation efficiency, drug loading efficiency, and GL-BSA content were studied. In addition, the morphology of the nanoparticles (NPs and weight loss rate were determined and Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy, and thermal analysis performed. Results: The average particle size of the sample NPs prepared under optimal conditions was 157.5 nm and the zeta potential was −22.51 ± 0.78 mV; the drug encapsulation efficiency and drug loading efficiency were 93.7% and 10.9%, respectively. The amount of GL coupling to BSA was 98.26 µg/mg. Through physical property study of the samples, we determined that the HCPT had been successfully wrapped in GL-BSA. In vitro drug-release study showed that the nanoparticles could release the drug slowly and continuously

  19. Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway.

    Science.gov (United States)

    Afnan, Quadri; Kaiser, Peerzada J; Rafiq, Rather A; Nazir, Lone A; Bhushan, Shashi; Bhardwaj, Subhash C; Sandhir, Rajat; Tasduq, Sheikh A

    2016-06-01

    Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B-induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1α, -1β and -6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-κB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA-treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-κB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-κB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Glycyrrhizic acid (GA) inhibits reactive oxygen Species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts.

    Science.gov (United States)

    Farrukh, Mufti Rana; Nissar, Ul-Ashraf; Kaiser, Peerzada J; Afnan, Quadri; Sharma, Praduman R; Bhushan, Shashi; Tasduq, Sheikh A

    2015-07-01

    Previously we have reported that generation of reactive oxygen species is the prime event responsible for calcium mediated activation of PERK-eIF2α-CHOP pathway and apoptosis in UV-B irradiated human skin fibroblasts (Hs68). We have also reported that glycyrrhizic acid (GA) mediates potent photoprotective activity against UV-B - irradiation-induced photodamage in human skin fibroblast. In the present study, we aimed to investigate the role of GA in preventing oxidative stress mediated unfolded protein response (UPR) and mitogen activated protein kinases (MAPK) pathway. Human skin fibroblast (Hs68) cells were exposed to UV-B radiations in lab conditions. Different parameters of UVB induced cellular and molecular changes were analysed using western-blotting, microscopy and flow cytometry. Our results show that GA has strong photoprotective action against UV-B induced cellular damage. It was observed that: (a) Oxidative disturbances and intracellular Ca(2+) imbalance induced by UV-B irradiation was significantly restored by GA treatment; (b) activation of PERK-eIF2α-CHOP and MAPK pathway induced by UV-B was significantly blocked by GA; (c) Loss of mitochondrial membrane potential and apoptosis induced by UV-B were reduced by GA treatment. Based on the above findings we conclude GA has a highly significant ROS quenching activity, thereby blocking the cascade of events including release of calcium from ER and subsequent ER stress, MAPK pathway and cellular demise. GA offers highly potent anti photodamage effect and can be exploited for cosmetic or therapeutic purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.

    Directory of Open Access Journals (Sweden)

    Rehan Khan

    Full Text Available BACKGROUND: Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH-induced precancerous lesions i.e., aberrant crypt foci (ACF and mucin depleted foci (MDF, and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. METHODS: Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks. RESULTS: GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin. CONCLUSION: Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.

  2. Simultaneous determination and assignment of 13 major flavonoids and glycyrrhizic acid in licorices by HPLC-DAD and Orbirap mass spectrometry analyses.

    Science.gov (United States)

    Wei, Shan-Shan; Yang, Min; Chen, Xin; Wang, Qiu-Rong; Cui, Ya-Jun

    2015-03-01

    To determine 13 flavonoids and glycyrrhizic acid in licorice (Glycyrrhiza spp.), several samples from different areas were examined by HPLC-DAD analysis. The analysis was performed on a Zorbax Extend-C18 (250 mm × 4.6 mm, 5 μm) column connected with a Zorbax Extend guard column (20 mm × 4.6 mm, 5 μm). The mobile phase consisted of (A) acetonitrile and (B) 0.026% aqueous H3PO4 (VV) using a gradient elution of 20%-25% A at 0-20 min, 25%-33% A at 20-30 min, 33%-50% A at 30-55 min, 50%-60% A at 55-65 min, and 60% A between 65 min and 80 min, and peaks were detected at 280 nm. The fourteen compounds were assigned by HPLC-Orbitrap MS methods. The regression coefficient for the linear equations for the 14 compounds ranged between 0.9998 and 1. The limits of detection and quantification lay in the range of 0.032-2.461 and 0.154-8.202 μg·mL(1), respectively. The relative recovery rates for the 14 compounds were in the range of 93.90%-106.73% with RSDs being less than 5%. Coefficient variations for intra-day and inter-day precisions were in the range of 0.27%-2.38% and 0.31%-3.51%, respectively. In summary, the validated method was applied to the simultaneous determination of the 14 components in 29 different licorice samples and was proven to be suitable for quality evaluation of licorices and their active fractions.

  3. 甘草酸对马钱子碱毒代动力学影响及解毒机制探讨%Study on the effect of glycyrrhizic acid on toxicokinetics for brucine and the mechanism study of detoxication

    Institute of Scientific and Technical Information of China (English)

    刘艳文; 颜苗; 李焕德; 雷艳青; 方平飞

    2012-01-01

    目的:研究甘草酸对中毒剂量下马钱子碱血浆、脑组织药动学的影响,探讨甘草酸解毒机制.方法:3组小鼠分别连续7d腹腔注射生理盐水、甘草酸溶液和维拉帕米溶液,第8天均腹腔注射马钱子碱溶液.UPLC-MS/MS法测定血浆和脑组织匀浆液中马钱子碱浓度.实时荧光定量PCR技术分析脑组织中P gp编码基因mdrla表达水平.结果:持续给予甘草酸使脑/血浓度比值曲线下面积较对照组减少37.6% (P<0.05),并可诱导小鼠脑组织mdrla mRNA的表达.P-gp抑制剂维拉帕米使脑内AUC0→10h、脑/血浓度比值曲线下面积分别增加了30.7%,32.5% (P<0.05).结论:甘草酸可能通过诱导血脑屏障上P-糖蛋白加速马钱子碱的脑部转运,维拉帕米阻止了马钱子碱从脑部的排出,马钱子碱可能是小鼠血脑屏障上P-gp底物.%OBJECTIVE To investigate the effects of glycyrrhizic acid on the kinetics of metabolism for toxic dosage of brucine in plasma and brain,and explore a new antidotal pathway for brucine-induced toxicity. METHODS Male KM mice were injected intraperitoneally with normal saline, glycyrrhizic acid and verapamil for 7 days, respectively. In the 8th day, each animal was injected intraperitoneally with brucine. UPLC-MS/MS method and real-time fluorescence quantitative RT-PCR methods were used to determinate the brucine's concentration and the expression of mdrla , respectively. RESULTS After treatment with glycyrrhizic acid,the AUC0→10h of brain/plasma concentration ratio decreased 37. 6% compaered to control group(P< 0. 05). The RT-PCR results revealed that continuesly treated with glycyrrhizic acid could induce the expression of mdrla mR-NA in the brain of mice. The AU0→10h. and the AUC0→10h of brain/plasma concentration ratio increased 30. 7% ,32. 5% respectively by verapamil(P<0. 05). CONCLUSION The experiment proved that glycyrrhizic acid may accelerate the elimination of brucine through up-regulate the P

  4. 住院患者甘草酸制剂相关低钾血症主动监测系统的建立%Establishment of an active monitoring system for glycyrrhizic acid preparation related hypokalemia in hospitalized patients

    Institute of Scientific and Technical Information of China (English)

    张帆; 王彦; 陈菲; 贾光伟

    2016-01-01

    Objective To establish an active monitoring system of glycyrrhizic acid preparation related hypokalemia in hospitalized patients. Methods The active monitoring system of glycyrrhizic acid preparation related hypokalemia in hospitalized patients was built based on the hospital information system (HIs),combined with Client/server( C/s)architecture,10g Oracle database,C # language,ODBC technology and DDL trigger. According to the pre-investigation's results,blood potassium <3. 5 mmol/L (A),using potassium supplement drugs(B)and sudden withdrawal(C)were as glycyrrhizic acid preparation related hypokalemia triggers. The trigger program was embedded into the HIs. The electronical medical record,s of all discharged patients from June 1,2014 to May 31,2015 were retrieved by two pharmacists-in-charge. The electronical medical records of the patients who used glycyrrhizic acid preparation were selected for trigger detection. The causality between glycyrrhizic acid preparation and kaliopenia in patients who were trigger detection positive were evaluated. The relevance ratio of ADR was counted, and compared with the actual reporting situation of glycyrrhizic acid preparation related hypokalemia at the same period. Results A total of 1405 cases were detected by the active monitoring system The cases comprised of 778 males and 627 females with age 1 to 94 years. The cases with age≤20, 21-40,41-60 and ≥61 were 86(6. 2%),419(29. 8%),492(35. 0%),and 408(29. 0%), respectively. The top three departments maximum number of cases were breast and thyroid surgery( 319 cases,22. 7%),department of gastroenterology( 192 cases,13. 7%),and department of infectious diseases(172 cases,12. 2%). The top three primary diseases were tumor(425 cases,30. 2%),chronic liver disease(263 cases,18. 7%),and abnormal liver function(239 cases,17. 0%). The top three amount of glycyrrhizic acid preparation were magnesium isoglycyrrhizinate injection ( 742 cases, 52. 8%), compound glycyrrhizin for injection

  5. 微波辅助胶团提取甘草中的甘草酸和甘草甙%Microwave-assisted Micellar Extraction and Determination of Glycyrrhizic Acid and Liquiritin in Licorice Root by HPLC

    Institute of Scientific and Technical Information of China (English)

    孙晨; 谢渝春; 刘会洲

    2007-01-01

    The feasibility of employing non-ionic surfactant (Triton X-100) as an alternative and effective solvent for the microwave-assisted extraction of glycyrrhizic acid (GA) and liquiritin (LQ) from licorice root was studied.The optimal extraction parameters based on the microwave-assisted micellar extraction technique were determined.Under the optimal conditions, i.e. 5% (by volume) Triton X-100, microwave-assisted extraction for 3-5min at 373K, the percentage extraction of active ingredients reached the highest value. The preconcentration factor for GA and LQ (about 13.5) and the extraction efficiency for these two ingredients approached 100% showed the coupling of microwave-assisted extraction and cloud-point extraction could be employed as a new and effective technique for the rapid extraction and preconcentration of pharmacologically active ingredients from medicinal plants such as licorice root without disturbing chromatographic analysis.

  6. Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignment (ACA) to rats.

    Science.gov (United States)

    Xu, Beilei; Li, Pengyue; Zhang, Guijun

    2015-04-15

    An LC-MS/MS method was developed for simultaneous analysis of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine of Gegenqinlian Decoction (GQD) and active components alignment (ACA) in rat plasma using hesperidin as the internal standard (I.S.). Chromatography was performed using a C18 column, with gradient elution with 1% acetic acid-0.001 mol/L ammonium acetate and acetonitrile at 0.2 ml/min. All analytes including I.S. were monitored under positive ionization conditions by selected reaction monitoring with an electrospray ionization source. The optimized mass transition ion-pairs (m/z) for quantitation were 471/297 for puerarin, 471/255 for daidzin, 447/271 for baicalin, 823/453 for glycyrrhizic acid, 419/257 for liquiritin, 336/320 for berberine, 352/336 for palmatine, 338/322 for jateorhizine and 611/303 for hesperidin. The calibration curves were linear over the concentration ranges from 0.15-63.0 to 6.3-6340.0 ng/mL. Intra-day and inter-day precisions (RSD%) were within 15.0%, and accuracy (RE%) ranged from -7.4 to 13.2%. The extraction recoveries were ranged from 60.4 to 93.3%. The proposed method was further applied to compare the pharmacokinetics of all analytes following a single oral administration of GQD and ACA. In conclusion, the eight analytes of GQD and ACA had partly similar pharmacokinetics, which were different from single composition (such as puerarin).

  7. Application of Acidic Treated Pumice as an Adsorbent for the Removal of Azo Dye from Aqueous Solutions:kinetic, Equilibrium and Thermodynamic Studies

    Directory of Open Access Journals (Sweden)

    Saied Bashiri

    2012-11-01

    Full Text Available Colored effluents are one of the important environment pollution sources since they contain unused dye compounds which are toxic and less-biodegradable. In this work removal of Acid Red 14 and Acid Red 18 azo dyes was investigated by acidic treated pumice stone as anefficient adsorbent at various experimental conditions. Removal of dye increased with increase in contact time and initial dye concentration, while decreased for increment in solution temperature and pH. Results of the equilibrium study showed that the removal ofAR14 and AR18 followed Freundlich (r2>0.99 and Langmuir (r2>0.99 isotherm models.Maximum sorption capacities were 3.1 and 29.7 mg/g for AR 14 and AR18, namely significantly higher than those reported in the literature, even for activated carbon. Fitting of experimental data onto kinetic models showed the relevance of the pseudo-second order (r2>0.99 and intra-particle diffusion (r2>0.98 models for AR14 and AR18, respectively. For both dyes, the values of external mass transfer coefficient decreased for increasing initial dye concentrations, showing increasing external mass transfer resistance at solid/liquid layer.Desorption experiments confirmed the relevance of pumice stone for dye removal, since the pH regeneration method showed 86% and 89 % regeneration for AR14 and AR18,respectively.

  8. Application of acidic treated pumice as an adsorbent for the removal of azo dye from aqueous solutions: kinetic, equilibrium and thermodynamic studies

    Directory of Open Access Journals (Sweden)

    Samarghandi Mohammad

    2012-11-01

    Full Text Available Abstract Colored effluents are one of the important environment pollution sources since they contain unused dye compounds which are toxic and less-biodegradable. In this work removal of Acid Red 14 and Acid Red 18 azo dyes was investigated by acidic treated pumice stone as an efficient adsorbent at various experimental conditions. Removal of dye increased with increase in contact time and initial dye concentration, while decreased for increment in solution temperature and pH. Results of the equilibrium study showed that the removal of AR14 and AR18 followed Freundlich (r2>0.99 and Langmuir (r2>0.99 isotherm models. Maximum sorption capacities were 3.1 and 29.7 mg/g for AR 14 and AR18, namely significantly higher than those reported in the literature, even for activated carbon. Fitting of experimental data onto kinetic models showed the relevance of the pseudo-second order (r2>0.99 and intra-particle diffusion (r2>0.98 models for AR14 and AR18, respectively. For both dyes, the values of external mass transfer coefficient decreased for increasing initial dye concentrations, showing increasing external mass transfer resistance at solid/liquid layer. Desorption experiments confirmed the relevance of pumice stone for dye removal, since the pH regeneration method showed 86% and 89% regeneration for AR14 and AR18, respectively.

  9. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. III. AYC aqueous coating onto granules and film formation mechanism of AYC.

    Science.gov (United States)

    Yuasa, Hiroshi; Kaneshige, Junichi; Ozeki, Tetsuya; Kasai, Takahide; Eguchi, Takahiro; Ishiwaki, Naomu

    2002-04-26

    From the viewpoint of effective utilization of natural resources and development of new pharmaceutical materials, acid-treated yeast cell wall (AYC) was prepared via a novel approach involving acidification of brewers' yeast cell wall. AYC aqueous dispersion containing 5% (w/v) AYC and 0.5% (w/v) glycerol was prepared. Subsequently, AYC was coated onto core granules containing acetaminophen (AAP). Spray mist size under various spray conditions and viscosity of the AYC aqueous dispersion at various AYC concentrations were measured. AYC spray mists were optically observed. The surface of AYC cast film and AYC-coated granules were observed with a confocal scanning laser microscope. We attempted to show the utility of AYC as a novel material for granule coating, following the tablet coating in our previous report. In addition, the film formation mechanism of AYC was investigated. A smooth surface of the AYC-coated granules was obtained at a coating ratio of only 5%, which generally requires approximately 15-30% coating against the core granule weight, with no aggregation. These results are attributable to the fact that the granules were coated with a large number of small mists of AYC and the coating progressed efficiently, and the thin film layer of AYC was formed on the granules by mutual tangling of the hydrogel layers of AYC polysaccharides. AAP release from AYC-coated granules was obviously rapid, suggesting the high utility of AYC as a coating material for the rapidly releasing granules.

  10. Graphene nanoplatelets prepared by electric heating Acid-treated graphite in a vacuum chamber and their use as additives in organic semiconductors.

    Science.gov (United States)

    Derry, Cameron; Wu, Yiliang; Gardner, Sandra; Zhu, Shiping

    2014-11-26

    Graphene nanoplatelets (GNPs) were prepared from acid-treated expandable graphite using a novel method of electric heating the graphite in an evaporation chamber under high vacuum, followed by solvent exfoliation. Such prepared graphene nanoplatelets, the eGNPs, were compared to GNPs prepared from two conventional methods: thermal expansion in an isothermal oven followed by solvent exfoliation (oGNPs), and direct solvent exfoliation (sGNPs), using various characterization techniques including UV-vis spectroscopy, scanning electron microscopy, and atomic force microscopy. It was found that the eGNPs were very thin, with a thickness of 4-16 nm, and showed no oxidation. On the other hand, oGNPs exhibited much thicker sheets, upward of 40 nm, and the sGNPs showed a high degree of oxidation. Utilizing the high purity eGNPs as an additive in PQT-12 semiconductor layer has been shown to improve the mobility by a factor of 2 in thin-film transistor devices.

  11. Evaluation of fermentation kinetics of acid-treated corn cob hydrolysate for xylose fermentation in the presence of acetic acid by Pichia stipitis.

    Science.gov (United States)

    Kashid, Mohan; Ghosalkar, Anand

    2017-08-01

    The efficient utilization of lignocellulosic biomass for ethanol production depends on the fermentability of the biomass hydrolysate obtained after pretreatment. In this work we evaluated the kinetics of ethanol production from xylose using Pichia stipitis in acid-treated corn cob hydrolysate. Acetic acid is one of the main inhibitors in corn cob hydrolysate that negatively impacts kinetics of xylose fermentation by P. stipitis. Unstructured kinetic model has been formulated that describes cell mass growth and ethanol production as a function of xylose, oxygen, ethanol, and acetic acid concentration. Kinetic parameters were estimated under different operating conditions affecting xylose fermentation. This is the first report on kinetics of xylose fermentation by P. stipitis which includes inhibition of acetic acid on growth and product formation. In the presence of acetic acid in the hydrolysate, the model accurately predicted reduction in maximum specific growth rate (from 0.23 to 0.15 h(-1)) and increase in ethanol yield per unit biomass (from 3 to 6.2 gg(-1)), which was also observed during experimental trials. Presence of acetic acid in the fermentation led to significant reduction in the cell growth rate, reduction in xylose consumption and ethanol production rate. The developed model accurately described physiological state of P. stipitis during corn cob hydrolysate fermentation. Proposed model can be used to predict the influence of xylose, ethanol, oxygen, and acetic acid concentration on cell growth and ethanol productivity in industrial fermentation.

  12. Simultaneous Extraction of Glabridin and Glycyrrhizic Acid from Glycyrrhiza glabra L.%同时提取光果甘草中光甘草定和甘草酸的工艺研究

    Institute of Scientific and Technical Information of China (English)

    李玉会; 徐德平; 张连富

    2011-01-01

    本文主要对光果甘草中光甘草定、甘草酸两种重要活性成分的同时提取工艺进行了研究.通过单因素试验确定了影响提取的主要因素及适宜水平范围,通过正交试验确定了其最佳提取条件为:用含0.6%氨水的60%乙醇溶液作为提取剂,料液比为1:20(w:v),在75℃条件下提取2 h.最佳提取条件下光甘草定的得率为0.238%±0.002%,甘草酸的得率为5.08%±0.03%.该工艺操作简单,投入一批原料,即可同时提取其中的光甘草定和甘草酸,为实现甘草资源高附加值的综合加工利用奠定了基础.%To study the technology of simultaneous extraction of glabridin and glycyrrhizic acid from Glycyrrhiza glabra L., the single factor experiments were done to determine the influencing factors and the orthogonal tests were done to optimize the extracting condition. The extraction conditions were optimized as follows:60% ethanol containing 0.6% ammonia as extractant,ratio of material to liquid 1:20 (w: v) ,extraction temperature 75 °C ,and duration was 2 h. Under these conditions,the extraction rates of Glabridin and Glycyrrhizic acid were 0.238 ±0.002% and 5.08 ±0.03% respectively. This technology featured simple operation and yielded the two important bioactive compounds at the same time. The research provided a basis for comprehensive development and utilization of Glycyrrhiza re sources with high valued-added.

  13. Equilibrium, kinetic and mass transfer studies and column operations for the removal of arsenic(III) from aqueous solutions using acid treated spent bleaching earth.

    Science.gov (United States)

    Mahramanlioglu, M; Güçlü, K

    2004-09-01

    In the present study, a new adsorbent was produced from spent bleaching earth by H2SO4 impregnation method. The sorption of arsenic(III) by acid treated spent bleaching earth was studied to examine the possibility of utilizing this material in water treatment systems. The effect of time, pH, initial concentration, temperature on the adsorption of arsenic(III) was studied. Maximum adsorption was found to occur at pH 9.0. The adsorption process followed the first order Lagergren equation. Mass transfer coefficients and rate constants of intraparticle diffusion were calculated. The experimental data points were fitted to the Langmuir equation in order to calculate the adsorption capacity (Q0) of the adsorbent and the value of Q0 was found to be 0.46 mmol g(-1). In order to understand the adsorption mechanism, Dubinin-Radushkevich (DR) isotherm was used. The magnitude of E calculated from DR equation was found to be 5.12 kJ mol(-1). The heat of adsorption (deltaH0 = -30367 J mol(-1)) implied that the adsorption was physical exothermic adsorption. The column studies were also carried out to simulate water treatment processes. The capacity values obtained in column studies were found to be greater than the capacity values obtained in batch studies. This result was explained by the difference between batch system and column system. The factors that affect the capacity values of column and batch systems were explained. The effect of other anions on the adsorption of arsenic(III) in the presence of NO3-, SO4(2-), Cl-, Br- was studied. The presence of these anions did not affect the adsorption of arsenic(III) significantly.

  14. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. II: effects of curing on the medicine release from AYC-coated tablets.

    Science.gov (United States)

    Yuasa, H; Kaneshige, J; Ozeki, T; Kasai, T; Eguchi, T; Ishiwaki, N

    2000-11-19

    Acid-treated yeast cell wall (AYC) was newly prepared by acidifying brewers' yeast cell wall. Core tablets containing 3% of acetaminophen (AAP) were coated with the AYC aqueous dispersion containing 5% (w/v) of AYC and 0.35% (w/v) of glycerol. The curing of AYC-coated tablets was performed at various curing periods of time and temperatures. The effects of curing on AAP release from AYC-coated tablets, the weight and thickness of the coated layer of AYC and the water sorption into the AYC-coated tablets were studied. The tensile strength and pore size distribution of the AYC cast film were measured. In the case of 60, 80, or 100 degrees C curing, AAP release from AYC-coated tablets showed a sigmoidal release profile with an initial lag time. The duration of the lag time increased with the increasing curing time and temperature, though the release rate after the lag time hardly changed. At 120 degrees C curing, the release rate after the lag time decreased with the increasing curing time and a sustained release was observed. The weight and thickness of the AYC-coated layer and the water sorption rate into AYC-coated tablets decreased with the increasing curing time and temperature. The tensile strength of the AYC cast film increased with increasing the curing temperature, particularly at 120 degrees C curing. It is considered that the water was evaporated from the AYC-coated layer and the adhesion force between AYC particles increased during curing, making the structure of the AYC-coated layer densely firm. The changes in the duration of lag time and the release rate may be due to changes in the structure of the AYC-coated layer caused by curing. These results show that it is feasible to control the lag time and the release rate of AAP from AYC-coated tablets by varying the curing time and temperature.

  15. On-site cellulase production by Trichoderma reesei 3EMS35 mutant and same vessel saccharification and fermentation of acid treated wheat straw for ethanol production

    Science.gov (United States)

    Khokhar, Zia-ullah; Syed, Qurat-ul-Ain; Wu, Jing; Athar, Muhammad Amin

    2014-01-01

    Bioethanol production from lignocellulosic raw materials involves process steps like pre-treatment, enzymatic hydrolysis, fermentation and distillation. In this study, wheat straw was explored as feedstock for on-site cellulase production by T. reesei 3EMS35 mutant, and as a substrate for second generation bioethanol production from baker yeast. Scanning electron microscopy (SEM) and X-ray diffractography (XRD) of untreated wheat straw (UWS) and acid treated wheat straw (TWS) were done to understand the structural organization and changes in the cellulase accessibility and reactivity. The effect of delignification and structural modification for on-site cellulase enzyme production was comparably studied. The efficiency of crude cellulase enzyme for digestion of UWS and TWS and then production of ethanol from TWS was studied using same-vessel saccharification and fermentation (SVSF) technique, both in shaking flasks as well as in fermenters. Two different methods of operation were tested, i.e. the UWSEnz method, where UWS was used for on-site enzyme production, and TWSEnz method where TWS was applied as substrate for cellullase production. Results obtained showed structural modifications in cellulose of TWS due to delignification, removal of wax and change of crystallinity. UWS was better substrate than TWS for cellulase production due to the fact that lignin did not hinder the enzyme production by fungus but acted as a booster. On-site cellulase enzyme produced by T. reesei 3EMS35 mutant hydrolyzed most of cellulose (91 %) in TWS within first 24 hrs. Shake flasks experiments showed that ethanol titers and yields with UWSEnz were 2.9 times higher compared to those obtained with TWSEnz method respectively. Comparatively, titer of ethanol in shake flask experiments was 10 % higher than this obtained in 3 L fermenter with UWSEnz. Outcomes from this investigation clearly demonstrated the potential of on-site cellulase enzyme production and SVSF for ethanol production

  16. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele;

    2012-01-01

    In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... were found to markedly distribute throughout the brain; this includes a number of BDDCS class 1 drugs shown to be Pgp substrates. This new perspective provides a further interpretation of how Pgp influences the sedative effects of H1-histamine receptor antagonists.......In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo...... outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB...

  17. PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES.

    Science.gov (United States)

    Hyatt, Michael W; Wiederhold, Nathan P; Hope, William W; Stott, Katharine E

    2017-06-01

    Aspergillosis is a common respiratory fungal disease in African penguins ( Spheniscus demersus ) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC0-24) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.

  18. Fate of orally administered radioactive fatty acids in the late-pregnant rat.

    Science.gov (United States)

    López-Luna, Pilar; Ortega-Senovilla, Henar; López-Soldado, Iliana; Herrera, Emilio

    2016-03-01

    To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [(14)C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL increased with time. Fetal plasma radioactivity increased with time, with its highest value at 8.0 h after DHA or LNA administration. DHA initially appeared primarily in the nonesterified fatty acids (NEFA) and PA, OA, LA, and LNA as TAG followed by NEFA; in all cases, there was an increase in PhL at later times. Measurement of fatty acid concentrations allowed calculation of specific (radio)activities, and the ratio (fetal/maternal) of these in the plasmas gave an index of placental transfer activity, which was LNA > LA > DHA = OA > PA. It is proposed that a considerable proportion of most fatty acids transferred through the placenta are released into the fetal circulation in the form of TAG.

  19. Corn oil and milk enhance the absorption of orally administered allyl isothiocyanate in rats.

    Science.gov (United States)

    Ippoushi, Katsunari; Ueda, Hiroshi; Takeuchi, Atsuko

    2013-11-15

    Allyl isothiocyanate, a chief component of mustard oil, exhibits anticancer effects in both cultured cancer cells and animal models. The accumulation of the N-acetylcysteine conjugate of allyl isothiocyanate, the final metabolite of allyl isothiocyanate, in urine was evaluated in rats that were orally coadministered allyl isothiocyanate with fluids (e.g., water, green tea, milk, and 10% ethanol) or corn oil. The N-acetylcysteine conjugate of allyl isothiocyanate content in urine when allyl isothiocyanate (2 or 4μmol) was coadministered with corn oil or milk showed a greater increase (1.4±0.22 or 2.7±0.34μmol or 1.2±0.32 or 2.5±0.36μmol, 1.6- to 1.8-fold or 1.5-fold, respectively) than when allyl isothiocyanate (2 or 4μmol) was coadministered with water (0.78±0.10 or 1.7±0.17μmol). This result demonstrates that corn oil and milk enhance the absorption of allyl isothiocyanate in rats.

  20. Safety evaluation of orally administered afoxolaner in 8-week-old dogs.

    Science.gov (United States)

    Drag, Marlene; Saik, Judith; Harriman, Jay; Larsen, Diane

    2014-04-02

    The safety profile of afoxolaner, a new isoxazoline molecule, was evaluated following the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3× or 5× the maximum exposure dose (6.3mg/kg) in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Treatments were administered at three, one-month dose intervals (Days 0, 28 and 56) followed by three, 2-week dose intervals (Days 84, 98 and 112). The study ended at Day 126. The groups were: Group 1: non-treated control; Group 2: afoxolaner chews administered at a dosage of at least 6.3mg/kg (1×); Group 3: afoxolaner chews administered at a dosage of at least 18.9 mg/kg (3×); and Group 4: afoxolaner chews administered at a dosage of at least 31.5mg/kg (5×). All dogs were examined for general health twice a day beginning on at least Day-14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner plasma concentrations, were performed throughout the study. On Day 126, 2 weeks following the last treatment, all dogs were humanely euthanized prior to the conduction of a full necropsy with tissue collection. No afoxolaner-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically or statistically significant health abnormalities related to the administration of afoxolaner were observed. Vomiting and diarrhea were observed sporadically across all groups including the controls. The kinetics of afoxolaner plasma concentrations was linear following 6 doses of 6.3, 18.9 and 31.5mg/kg and dose proportionality was demonstrated. There were no statistical differences (pafoxolaner was shown to be safe when administered repeatedly in a soft chewable formulation at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.

  1. Assessment of the efficacy of orally administered afoxolaner against Rhipicephalus sanguineus sensu lato.

    Science.gov (United States)

    Kunkle, Bruce; Daly, Sean; Dumont, Pascal; Drag, Marlene; Larsen, Diane

    2014-04-02

    Two studies were conducted to confirm that a single oral dose of the novel insecticide/acaricide afoxolaner is efficacious against existing infestations of Rhipicephalus sanguineus sensu lato in dogs and can control re-infestation for up to 35 days. Each study utilized 16 purpose bred adult dogs using a controlled randomized block design. One or two days prior to treatment, all dogs were infested with 50 unfed adult ticks. On Day 0 one group was treated with an oral chewable formulation of afoxolaner at a dose as close as possible to the minimum dose of 2.5mg/kg. Weekly re-infestations with 50 adult unfed ticks were repeated for five weeks. Forty-eight hours after treatment and after each re-infestation, the number of remaining live ticks on each dog was counted. Treatment with afoxolaner resulted in efficacies of 98.8-100% within 48 h on existing tick infestations, while the efficacy against new tick infestations was >95.7% over five weeks.

  2. Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs.

    Science.gov (United States)

    Drag, M; Saik, J; Harriman, J; Letendre, L; Yoon, S; Larsen, D

    2016-11-27

    The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28-day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14-day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham-dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day -14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment-related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.

  3. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs.

    Science.gov (United States)

    McTier, Tom L; Chubb, Nathan; Curtis, Michael P; Hedges, Laura; Inskeep, Gregory A; Knauer, Christopher S; Menon, Sanjay; Mills, Brian; Pullins, Aleah; Zinser, Erich; Woods, Debra J; Meeus, Patrick

    2016-05-30

    The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11-12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25-5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs.

  4. Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a-/-mice

    Institute of Scientific and Technical Information of China (English)

    Kelley; MK; Haarberg; Meghan; J; Wymore; Brand; Anne-Marie; C; Overstreet; Catherine; C; Hauck; Patricia; A; Murphy; Jesse; M; Hostetter; Amanda; E; Ramer-Tait; Michael; J; Wannemuehler

    2015-01-01

    AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice.

  5. Assessment of vitamin B(12) absorption based on the accumulation of orally administered cyanocobalamin on transcobalamin.

    Science.gov (United States)

    Hardlei, Tore Forsingdal; Mørkbak, Anne Louise; Bor, Mustafa Vakur; Bailey, Lynn B; Hvas, Anne-Mette; Nexo, Ebba

    2010-03-01

    Vitamin B(12), or cobalamin (Cbl), is absorbed in the intestine and transported to the cells bound to transcobalamin (TC). We hypothesize that cyanocobalamin (CNCbl) is absorbed unchanged, thereby allowing measurement of the complex of CNCbl bound to TC (TC-CNCbl) to be used for studying the absorption of the vitamin. TC was immunoprecipitated from serum samples obtained from healthy donors at baseline and at 24 h after oral administration of three 9-microg CNCbl doses over 1 day. Cbl was released by treatment with subtilisin Carlsberg. The different forms of Cbl were isolated by HPLC and subsequently quantified with an ELISA-based Cbl assay. At baseline, the median TC-CNCbl concentration was 1 pmol/L (range, 0-10 pmol/L); the intraindividual variation (SD) was 1.6 pmol/L (n = 31). After CNCbl administration, the TC-CNCbl concentration increased significantly (P = 0.0003, paired t-test), whereas no major changes were observed in any of the other Cbl forms bound to TC (n = 10). Only a moderate additional increase in TC-CNCbl was observed with prolonged (5 days) CNCbl administration (n = 10). We designed an absorption test based on measuring TC-CNCbl at baseline and 24 h after CNCbl intake and established a reference interval for the increase in TC-CNCbl (n = 78). The median absolute increase was 23 pmol/L (range, 6-64 pmol/L), and the relative increase was >3-fold. Our data demonstrate that CNCbl is absorbed unchanged and accumulates on circulating TC. We suggest that measuring TC-CNCbl will improve the assessment of vitamin B(12) absorption.

  6. Modulation of human humoral immune response through orally administered bovine colostrum.

    Science.gov (United States)

    He, F; Tuomola, E; Arvilommi, H; Salminen, S

    2001-08-01

    Eighteen healthy volunteers were randomized into two treatment groups and consumed liquid prepackaged bovine colostrum whey and placebo for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine was given to all subjects to mimic an enteropathogenic infection. The circulating antibody secreting cells and the expression of phagocytosis receptors of the subjects before and after oral immunization were measured with the ELISPOT assay and flow cytometry. All subjects responded well to the vaccine. No significant differences were observed in ELISPOT values for IgA, IgG, IgM, Fcgamma and CR receptor expression on neutrophils and monocytes between the two groups. There was a trend towards greater increase in specific IgA among the subjects receiving their vaccine with bovine colostrum. These results suggest that bovine colostrum may possess some potential to enhance human special immune responses.

  7. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    Science.gov (United States)

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  8. Orally administered novel cyclic pentapeptide P-317 alleviates symptoms of diarrhoea-predominant irritable bowel syndrome.

    Science.gov (United States)

    Zielińska, Marta; Chen, Chunqiu; Mokrowiecka, Anna; Cygankiewicz, Adam I; Zakrzewski, Piotr K; Sałaga, Maciej; Małecka-Panas, Ewa; Wlaź, Piotr; Krajewska, Wanda M; Fichna, Jakub

    2015-02-01

    The aim of our study was to characterize the effect of P-317, a novel cyclic derivative of morphiceptin, on gastrointestinal (GI) motility and abdominal pain in mouse models mimicking symptoms of diarrhoea-predominant irritable bowel syndrome (IBS-D). The effect of P-317 on mouse intestinal motility was characterized in vitro and in vivo in physiological and pathophysiological conditions. The antinociceptive action of P-317 was characterized in the mustard oil-induced abdominal pain model and the writhing test. Locomotor activity and grip-strength tests were used to evaluate the effect of P-317 in the central nervous system (CNS). To translate our study to clinical conditions, the semi-quantitative expression of μ-opioid receptors (MOP) and κ-opioid receptors (KOP) messenger RNA (mRNA) in human colonic samples from IBS-D patients was quantified. In vitro, P-317 (10(-10) -10(-6) M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent, β-funaltrexamine and nor-binaltorphimine-reversible manner. In vivo, P-317 (0.1 mg/kg, i.p. and 1 mg/kg, p.o.) inhibited GI transit, displayed a potent antinociceptive action in abdominal pain tests and did not influence the CNS. P-317 produced a potent analgesic and antidiarrhoeal action in the mouse GI tract after oral administration. Given lower expression of MOP and KOP mRNA in IBS-D patients, P-317 is a promising peptide-based drug candidate for IBS-D therapy. © 2014 Royal Pharmaceutical Society.

  9. Orally administered Lactobacillus strains differentially affect the direction and efficacy of the immune response

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten, J.C.A.M. van; Balk, F.; Heijne den Bak-Glashouwer, M.J.; Leer, R.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    1998-01-01

    In mice, strain dependent cytokine production profiles are induced after oral administration of Lactobacillus. Such a cytokine profile seems to determine the direction and efficacy of the humoral response. In SJL mice lactobacilli are able to enhance or inhibit the development of disease after

  10. Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

    2015-03-01

    Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

  11. Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

    OpenAIRE

    Razavi M; Karimian H; Yeong CH; Fadaeinasab M; Khaing SL; Chung LY; Mohamad Haron DE; Noordin MI

    2016-01-01

    Mahboubeh Razavi,1 Hamed Karimian,1 Chai Hong Yeong,2 Mehran Fadaeinasab,3 Si Lay Khaing,4 Lip Yong Chung,1 Didi Erwandi B Mohamad Haron,5 Mohamed Ibrahim Noordin1,6 1Department of Pharmacy, 2University Malaya Research Imaging Centre and Department of Biomedical Imaging, Faculty of Medicine, 3Center for Natural Product Research and Drug Discovery (CENAR), 4Department of Obstetrics & Gynaecology, 5Shimadzu-UMMC Centre for Xenobiotics Studies, Pharmacology Department, Faculty of Medicin...

  12. Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

    Directory of Open Access Journals (Sweden)

    Razavi M

    2016-12-01

    Full Text Available Mahboubeh Razavi,1 Hamed Karimian,1 Chai Hong Yeong,2 Mehran Fadaeinasab,3 Si Lay Khaing,4 Lip Yong Chung,1 Didi Erwandi B Mohamad Haron,5 Mohamed Ibrahim Noordin1,6 1Department of Pharmacy, 2University Malaya Research Imaging Centre and Department of Biomedical Imaging, Faculty of Medicine, 3Center for Natural Product Research and Drug Discovery (CENAR, 4Department of Obstetrics & Gynaecology, 5Shimadzu-UMMC Centre for Xenobiotics Studies, Pharmacology Department, Faculty of Medicine, University of Malaya, 6Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm, National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Penang, Malayasia Abstract: This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl, using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP:xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP,3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax at which the maximum concentration of metformin HCl in the blood (Cmax was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP,3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.Keywords: drug delivery systems, floating system, gastric retention, sustained release natural polymers, evaluation in vitro and in vivo

  13. Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy.

    Science.gov (United States)

    Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

    2017-01-01

    This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. (153)Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.

  14. The pharmacokinetics of orally administered ivermectin in African elephants (Loxodonta africana): implications for parasite elimination.

    Science.gov (United States)

    Gandolf, A Rae; Lifschitz, A; Stadler, C; Watson, B; Galvanek, L; Ballent, M; Lanusse, C

    2009-03-01

    Loxodonta africana are susceptible to a wide variety of parasites that are often treated with the broad spectrum antiparasitic ivermectin (IVM) based on empirical knowledge. The objectives of this study were to 1) measure plasma IVM levels following administration of 0.1 mg/kg IVM p.o., 2) compare plasma IVM levels following administration with regular versus restricted feed rations, 3) measure IVM excretion in feces, and 4) use these findings to generate dosing recommendations for this species. Using a crossover design, six African elephants were divided into two groups. Ivermectin was administered and typical grain rations were either provided or withheld for 2 hr. Blood and fecal samples were collected for 7 days following drug administration. After a 5-wk washout period, groups were switched and the procedure repeated. Plasma and fecal IVM were analyzed using high-performance liquid chromatography. There was no statistically significant difference detected in the pharmacokinetic data between the fed and fasted groups. Peak plasma concentration, area under the curve, and half-life for plasma ranged between 5.41-8.49 ng/ml, 17.1-20.3 ng x day/ml, and 3.12-4.47 day, respectively. High IVM concentrations were detected in feces. The peak concentration values in feces were between 264-311-fold higher than those obtained in plasma. The comparatively large area under the curve and short time to maximum concentration in feces indicate elimination prior to absorption of much of the drug. Plasma IVM concentrations were low when compared to other species. Based on these findings, administration of 0.2-0.4 mg/kg p.o. should be appropriate for eliminating many types of parasites in elephants, and could minimize development of parasite resistance.

  15. Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus).

    Science.gov (United States)

    Bechert, Ursula; Christensen, J Mark; Nguyen, C; Neelkant, R; Bendas, E

    2008-06-01

    The pharmacokinetic parameters of phenylbutazone were determined in 18 elephants (Loxodonta africana and Elephas maximus) after single-dose oral administration of 2, 3, and 4 mg/kg phenylbutazone, as well as multiple-dose administrations with a 4-wk washout period between trials. After administration of 2 mg/kg phenylbutazone, mean serum concentrations peaked in approximately 7.5 hr at 4.3 +/- 2.02 microg/ml and 9.7 hr at 7.1 +/- 2.36 microg/ml for African and Asian elephants, respectively, while 3 mg/kg dosages resulted in peak serum concentrations of 7.2 +/- 4.06 microg/ml in 8.4 hr and 12.1 +/- 3.13 microg/ml in 14 hr. The harmonic mean half-life was long, ranging between 13 and 15 hr and 39 and 45 hr for African and Asian elephants, respectively. There was evidence of enterohepatic cycling of phenylbutazone in Asian elephants. Significant differences (P < 0.0001) in pharmacokinetic values occurred between African and Asian elephants for clearance (27.9 and 7.6 ml/hr/kg, respectively), terminal half-life (15.0 and 38.7 hr, respectively), and mean residence time (22.5 and 55.5 hr, respectively) using 2-mg/kg dosages as an example. This suggests that different treatment regimens for Asian and African elephants should be used. There were no apparent gender differences in these parameters for either elephant species.

  16. Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus).

    Science.gov (United States)

    Bechert, Ursula; Christensen, J Mark

    2007-06-01

    The pharmacokinetic parameters of S(+) and R(-) ibuprofen were determined in 20 elephants after oral administration of preliminary 4-, 5-, and 6-mg/kg doses of racemic ibuprofen. Following administration of 4 mg/kg ibuprofen, serum concentrations of ibuprofen peaked at 5 hr at 3.9 +/- 2.07 microg/ml R(-) and 10.65 +/- 5.64 microg/ml S(+) (mean +/- SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 +/- 1.39 microg/ml R(-) and 13.77 +/- 3.75 microg/ml S(+) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 +/- 2.17 microg/ml R(-) and 14.82 +/- 9.71 microg/ml S(+) in African elephants, and 5.72 +/- 1.60 microg/ml R(-) and 18.32 +/- 10.35 microg/ml S(+) in Asian elephants. Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.2-2.4 hr R(-) and 4.5-5.1 hr S(+) in African elephants and 2.4-2.9 hr R(-) and 5.9-7.7 hr S(+) in Asian elephants. Serum concentrations of R(-) ibuprofen were undetectable at 24 hr, whereas S(+) ibuprofen decreased to below 5 microg/ml 24 hr postadministration in all elephants. The volume of distribution was estimated to be between 322 and 356 ml/kg R(-) and 133 and 173 ml/kg S(+) in Asian elephants and 360-431 ml/kg R(-) and 179-207 ml/kg S(+) in African elephants. Steady-state serum concentrations of ibuprofen ranged from 2.2 to 10.5 microg/ml R(-) and 5.5 to 32.0 microg/ml S(+) (mean: 5.17 +/- 0.7 R(-) and 13.95 +/- 0.9 S(+) microg/ml in African elephants and 5.0 +/- 1.09 microg/ml R(-) and 14.1 +/- 2.8 microg/ml S(+) in Asian elephants). Racemic ibuprofen administered at 6 mg/kg/12 hr for Asian elephants and at 7 mg/kg/12 hr for African elephants results in therapeutic serum concentrations of this antiinflammatory agent.

  17. Orally administered whole egg demonstrates antidepressant-like effects in the forced swimming test on rats.

    Science.gov (United States)

    Nagasawa, Mao; Otsuka, Tsuyoshi; Ogino, Yumi; Yoshida, Junki; Tomonaga, Shozo; Yasuo, Shinobu; Furuse, Mitsuhiro

    2014-08-01

    Several studies have reported that vegetarian diets are associated with a higher prevalence of major depression. Therefore, we hypothesised that the consumption of animal products, especially eggs, may have positive effects on mental health, especially on major depression, because a previous study reported that egg consumption produces numerous beneficial effects in humans. The purpose of the present study was to evaluate the effects of chronic whole-egg treatment on depression-like behaviours in Wistar rats, a control strain, and Wistar Kyoto rats, an animal model of depression. In both the rats, either whole-egg solution (5 ml/kg) or distilled water (5 ml/kg) was orally administrated for 35 days. During these periods, the open-field test (OFT) was conducted on the 21st day, and a forced swimming test (FST) was enforced on the 27th and 28th days. On the 36th day, the plasma and brain were collected. Chronic whole-egg treatment did not affect line crossing in the OFT, whereas it reduced the total duration of immobility in the FST on both strains. Furthermore, interestingly, the results indicated the possibility that whole-egg treatment elevated the incorporation of tryptophan into the brain, and the tryptophan concentration in the prefrontal cortex was actually increased by the treatment. This study demonstrated that whole-egg treatment exerts an antidepressant-like effect in the FST. It is suggested that whole egg may be an excellent food for preventing and alleviating the conditions of major depression.

  18. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for

  19. MRI of colorectal cancer liver metastases: comparison of orally administered manganese with intravenously administered gadobenate dimeglumine

    Energy Technology Data Exchange (ETDEWEB)

    Brismar, Torkel B.; Kartalis, Nikolaos; Albiin, Nils [Karolinska Institutet, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden); Kylander, Christian [Karolinska Institutet, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden)

    2012-03-15

    To compare the sensitivity of MRI to detect colorectal cancer liver metastases (CRLM) after ingestion of manganese-based contrast agent (CMC-001) with that of a comprehensive intravenous gadobenate dimeglumine protocol, and to assess the safety and acceptability of oral manganese. 20 patients suspected of having 1-6 CRLM were included prospectively in this randomised cross-over study. Liver MRI was performed with a one-week interval at 1.5 T and included T1-w VIBE and T2-HASTE, before and after administration of 1.6 g CMC-001 or 0.1 mmol/kg gadobenate dimeglumine. The metastasis-to-liver signal intensity (SI) ratio was calculated. Standard of reference was histopathology after surgery, or combination of other imaging studies and/or follow up. Adverse events (AE) and clinicolaboratory tests were monitored. Of 44 metastases, 41 were detected after CMC-001 (93%) and 42 after gadobenate dimeglumine (95%). Fifteen false-positive lesions were found after CMC-001 and 2 after gadobenate dimeglumine. The metastasis-to-liver SI ratio was significantly higher after CMC-001 than after gadobenate dimeglumine (0.51 and 0.21 respectively, P < 0.0001). More AE occurred after manganese compared to gadobenate dimeglumine. CMC-001 is as sensitive as an extensive intravenous gadobenate dimeglumine protocol in detecting CRLM. It was relatively well tolerated but had higher rates of gastrointestinal AE. (orig.)

  20. Triple Recycling Processes Impact Systemic and Local Bioavailability of Orally Administered Flavonoids.

    Science.gov (United States)

    Dai, Peimin; Zhu, Lijun; Luo, Feifei; Lu, Linlin; Li, Qiang; Wang, Liping; Wang, Ying; Wang, Xinchun; Hu, Ming; Liu, Zhongqiu

    2015-05-01

    Triple recycling (i.e., enterohepatic, enteric and local recycling) plays a central role in governing the disposition of phenolics such as flavonoids, resulting in low systemic bioavailability but higher gut bioavailability and longer than expected apparent half-life. The present study aims to investigate the coexistence of these recycling schemes using model bioactive flavonoid tilianin and a four-site perfused rat intestinal model in the presence or absence of a lactase phlorizin hydrolase (LPH) inhibitor gluconolactone and/or a glucuronidase inhibitor saccharolactone. The result showed that tilianin could be metabolized into tilianin glucuronide, acacetin, and acacetin glucuronide, which are excreted into the bile and luminal perfusate (highest in the duodenum and lowest in the colon). Gluconolactone (20 mM) significantly reduced the absorption of tilianin and the enteric and biliary excretion of acacetin glucuronide. Saccharolactone (0.1 mM) alone or in combination of gluconolactone also remarkably reduced the biliary and intestinal excretion of acacetin glucuronide. Acacetin glucuronides from bile or perfusate were rapidly hydrolyzed by bacterial β-glucuronidases to acacetin, enabling enterohepatic and enteric recycling. Moreover, saccharolactone-sensitive tilianin disposition and glucuronide deconjugation, which was more active in the small intestine than the colon, points to the small intestinal origin of the deconjugation enzyme and supports the presence of local recycling scheme. In conclusion, our studies have demonstrated triple recycling of a bioactive phenolic (i.e., a model flavonoid), and this recycling may have an impact on the site and duration of polyphenols pharmacokinetics in vivo.

  1. Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer.

    Science.gov (United States)

    Marshall, J L; Wellstein, A; Rae, J; DeLap, R J; Phipps, K; Hanfelt, J; Yunmbam, M K; Sun, J X; Duchin, K L; Hawkins, M J

    1997-12-01

    Tumor angiogenesis is critically important to tumor growth and metastasis. We have shown that pentosan polysulfate (PPS) is an effective inhibitor of heparin-binding growth factors in vitro and can effectively inhibit the establishment and growth of tumors in nude mice. Following completion of our Phase I trial of s.c. administered PPS, we performed a Phase I trial of p.o. administered PPS in patients with advanced cancer to determine the maximum tolerated dose (MTD) and toxicity profile and to search for any evidence for biological activity in vivo. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m2. Patients were monitored at least every 2 weeks with physical exams and weekly with hematological, chemistry, stool hemoccult, and coagulation blood studies, and serum and urine samples for PPS and basic fibroblastic growth factor (bFGF) levels were also taken. The PPS dose was escalated in an attempt to reach the MTD. Eight additional patients were enrolled at the highest dose to further characterize the toxicity profile and biological in vivo effects of PPS. A total of 21 patients were enrolled in the three cohorts of doses 180 (n = 4), 270 (n = 3), and 400 (n = 14) mg/m2. The most severe toxicities seen were grade 3 proctitis and grade 4 diarrhea; however, 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels. There were no objective responses, although three patients had prolonged stabilization of previously progressing disease. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration. Serum and urine bFGF levels failed to show a consistent, interpretable pattern; however the data suggested an inverse relationship between PPS and bFGF levels in vivo. A MTD could not be determined using the daily t.i.d. dosing schedule due to the development of grade 3/4 GI toxicity (proctitis) at all dose levels studied. PPS, administered p.o. at doses of 400 mg/m2 t.i.d., did not cause significant systemic toxicity, but most patients developed moderate-to-severe GI toxicity within 1-2 months. The cause of the GI toxicity was unclear, but it was readily reversible upon cessation of the agent. The suggestion of an inverse relationship between PPS and bFGF supports further study of PPS as an antiangiogenic agent. The tested doses and schedule cannot be recommended for further study. Subsequent murine experiments showed PPS to be more effective as an anticancer agent when it is given intermittently. We propose a study of PPS given on a weekly schedule in further clinical trials.

  2. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  3. Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose

    NARCIS (Netherlands)

    Brouwer, DAJ; van Beek, J; Ferwerda, H; Brugman, AM; van der Klis, FRM; Muskiet, FAJ

    1998-01-01

    We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 mu g cholecalciferol/d for 14 d and were subsequently studied for a further 88 d

  4. Estimation of parameters for the elimination of an orally administered test substance with unknown absorption.

    Science.gov (United States)

    Vogt, Josef A; Denzer, Christian

    2013-04-01

    Assessment of the elimination of an oral test dose based on plasma concentration values requires correction for the effect of gastric release and absorption. Irregular uptake processes should be described 'model independently', which requires estimation of a large number of absorption parameters. To limit the associated computational effort a new approach is developed with a reduced number of unknown parameters. A marginalized and regularized absorption approach (MRA) is defined, which uses for the uptake just one parameter to control rigidity of the uptake curve. For validation, elimination and absorption were reproduced using published IVIVC data and a synthetic data set for comparison with approaches using a 'model-free'--staircase function or mechanistic models to describe absorption. MRA performed almost as accurate as well specified mechanistic models, which gave the best reproduction. MRA demonstrated a 50fold increase in computational efficiency compared to other approaches. The absorption estimated for the IVIVC study demonstrated an in vivo-in vitro correlation comparable to published values. The newly developed MRA approach can be used to efficiently and accurately estimate elimination and absorption with a restricted number of adaptive parameters and with automatic adjustment of the complexity of the uptake.

  5. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    OpenAIRE

    Chun-Yan Yeung; Wai-Tao Chan; Chun-Bin Jiang; Mei-Lien Cheng; Chia-Yuan Liu; Szu-Wen Chang; Jen-Shiu Chiang Chiau; Hung-Chang Lee

    2015-01-01

    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orall...

  6. Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

    Science.gov (United States)

    Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

    2017-01-01

    This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region. PMID:28031701

  7. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmun

  8. Orally administered S-1 suppresses circulating endothelial cell counts in metastatic breast cancer patients.

    OpenAIRE

    2013-01-01

    [Background]S-1 is an oral cytotoxic preparation that contains tegafur. Gamma-butyrolactone (GBL) is a metabolite of tegafur that is known to suppress vascular endothelial growth factor (VEGF)-mediated angiogenic activity. The aim of this study was to determine the change in circulating endothelial cell (CEC) counts, GBL levels, and angiogenesis-related factors during S-1 administration in metastatic breast cancer (MBC) patients. [Methods]Patients with HER2-negative MBC were eligible. S-1 was...

  9. 5-Caffeoylquinic acid and caffeic acid orally administered suppresses P-selectin expression on mouse platelets

    Science.gov (United States)

    Caffeic acid and 5-caffeoylquinic acid are a naturally occurring phenolic acid and its ester found in human diets. In this paper, potential effects of caffeic acid and 5-caffeoylquinic acid found in coffee and other plant sources on platelet activation were studied via investigating P-selectin expre...

  10. Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease

    Science.gov (United States)

    Si, Xiao-Ying; Merlin, Didier; Xiao, Bo

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic relapsing disease in gastrointestinal tract. Conventional medications lack the efficacy to offer complete remission in IBD therapy, and usually associate with serious side effects. Recent studies indicated that nanoparticle-based nanotherapeutics may offer precise and safe alternative to conventional medications via enhanced targeting, sustained drug release, and decreased adverse effects. Here, we reviewed orally cell-specific nanotherapeutics developed in recent years. In addition, the various obstacles for oral drug delivery are also reviewed in this manuscript. Orally administrated cell-specific nanotherapeutics is expected to become a novel therapeutic approach for IBD treatment. PMID:27678353

  11. Effectiveness of orally administered cupric oxide needles in alleviating hypocupraemia in sheep and cattle.

    Science.gov (United States)

    Suttle, N F

    1981-05-09

    The oral administration of a small dose of cupric oxide "needles" (CuOn), providing 0.5 g copper, to hypocupraemic ewes maintained on a copper-deficient diet alleviated hypocupraemia for 111 days when the diet was supplemented with molybdenum and sulphate and for 301 days when the diet was not supplemented. The same amount of copper given as cupric sulphate was approximately half as effective. The administration of a large dose of CuOn, providing 40 g copper, to hypocupraemic steers and heifers alleviated hypocupraemia for not less than 41 days, at which time a substantial reserve of copper (428 mg) remained in the liver. The absorbability of copper in CuOn was estimated to be 8.3 per cent and 3.8 per cent (depending on diet) for sheep. It was calculated that enough absorbable copper could be provided in a single dose to meet the net copper requirements of ewes for several years. This new form of copper therapy demands a totally different approach from that associated with parenteral copper usage.

  12. Bioavailability of ketoprofen from orally administered ketoprofen-dextran ester prodrugs in the pig

    DEFF Research Database (Denmark)

    Larsen, C.; Jensen, Bodil Hamborg; Olesen, H. P.

    1991-01-01

    The bioavailability of ketoprofen after oral administration of aqueous solutions of various ketoprofen-dextran ester prodrugs in pigs was assessed. Conjugates derived from dextran fractions in the molecular weight range 10,000-500,000 were employed. Compared to the administration of an oral......-dextran esters. Thus, the present study adds support to a more versatile application of the dextran ester prodrug approach to providing selective colon delivery of drugs possessing a carboxylic acid functional group....

  13. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmun

  14. Assessment of the effects of orally administered ferrous sulfate on Oncopeltus fasciatus (Heteroptera: Lygaeidae).

    Science.gov (United States)

    Ferrero, Amparo; Torreblanca, Amparo; Garcerá, María Dolores

    2017-03-01

    Iron is an essential nutrient needed for multiple biological processes, but it is also an effective pro-oxidant in its reduced form. Environmental sources of iron toxic species include reduced soils from rice plantations, polluted natural areas from metal industry waste, or iron oxides used in soil bioremediation. Few studies have been conducted to assess the toxicity of iron species in insects. The present work aims to assess the oxidative stress effects of ferrous sulfate administered in drinking water after acute exposure (96 h) to adults of the insect model Oncopeltus fasciatus (Dallas). Mortality was higher in exposed groups and significantly associated with iron treatment (OR [95% CI]; 11.8 [6.1-22.7]). Higher levels of body iron content were found in insects exposed to ferrous sulfate, with an increase of 5-6 times with respect to controls. Catalase activity and lipid peroxidation (TBARS content), but not glutathione S-transferase activity, were significantly higher in exposed insects and significantly correlated with body iron content (Pearson coefficient of 0.68 and 0.74, respectively) and between them (0.78). The present work demonstrates that, despite the disruption in water and food intake caused by iron administration, this metal is accumulated by insect causing lipid peroxidation and eliciting an antioxidant response mediated by catalase.

  15. Antiosteoporotic effect of orally administered yolk-derived peptides on bone mass in women.

    Science.gov (United States)

    Abdou, Adham M; Watabe, Kazuya; Yamane, Tetsuro; Isono, Tadayuki; Okamura, Yoshitaka; Kawahito, Seiji; Takeshima, Kazuhito; Masuda, Kazuyuki; Kim, Mujo

    2014-05-01

    The main objective of this study was to verify the effect of oral intake of a yolk-derived peptide preparation (HYP) obtained by enzymatic hydrolysis of yolk water-soluble protein on bone markers and bone density in 65 perimenopausal women with an average age of 47.6 ± 5.2 years. Subjects were divided into three groups, and then enrolled in a 6-month, randomized, double-blind clinical trial. Bone formation and resorption markers were measured at 0, 3, and 6 months, while bone mineral density (BMD) in the lumbar spines was measured at 0 and 6 months. Although the bone formation marker levels showed the similarity changes among the groups, bone resorption markers in the test HYP group were significantly decreased after 3 and 6 months in comparison to other groups (P < 0.05). After 6 months, BMD in the test HYP group maintained at healthy numerical values whereas BMD values were decreased in other groups. Hence HYP would be an antiosteoporotic agent originated from natural food to maintain bone health, especially for women.

  16. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model

    Science.gov (United States)

    Jiang, Chun-Bin; Cheng, Mei-Lien; Liu, Chia-Yuan; Chang, Szu-Wen; Chiang Chiau, Jen-Shiu; Lee, Hung-Chang

    2015-01-01

    Background and Aims Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model. Methods Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation. Results Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (Pprobiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (Pprobiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future. PMID:26406888

  17. 变换波长高效液相色谱法测定八味檀香散中丁香酚和甘草酸的含量%Determination of Eugenol and Glycyrrhizic Acid in Bawei Tanxiang San by HPLC

    Institute of Scientific and Technical Information of China (English)

    薛克昌; 王杰松; 史宁; 谭生建; 吴久鸿

    2011-01-01

    目的 建立高效液相色谱法同时测定八味檀香散中丁香酚和甘草酸含量的方法.方法 采用Agilent ZORBAX Eclipse SB-C18(4.6 mm × 150 mm,μm)色谱柱.流动相为乙腈-5%乙腈(含3%冰醋酸)(27:73);流速1 mL·min-1,检测波长程序:0~17.0 min为280 nm,17.0~30 min为250 nm.结果 丁香酚和甘草酸保留时间分别约为15和21 min,与各自相邻峰的分离度均大于1.5.以峰面积对进样质量浓度(μg·mL-1)线性回归,丁香酚回归方程:Y=0.106 4p-1.338,r=0.999 9,线性范围77.76~777.6μg·mL-1.甘草酸回归方程:Y=0.133 9p-0.222 0,r=0.999 9,线性范围14.40~144.0 μg·mL-1.丁香酚和甘草酸的回收率分别为99.0%和97.3%、RSD分别为1.5%和1.8%.结论 本法操作简便,测定结果准确,重复性好,可用于八味檀香散中丁香酚和甘草酸的含量测定.%OBJECTIVE To establish a HPLC quantitative method for the determination of eugenol and glycyrrhizic acid in Bawei Tanxiang San simultaneously. METHODS The separation was performed on an Agilent ZORBAX Eclipse SB-C18 column(4. 6 mm ×150 mm,5 μm) with the mobile phase consisting of acetonitrile -5% acetonitrile( include 3% glacialacetic acid)(27:73 ). The flow rate was 1 mL · min -1 and the detection wavelength was at 280 nm(0 ~17.0 min) , 250 nm(17.1 ~30 min). RESULTS The retention time of eugenol and glycyrrhizic acid was about 15 min and 21 ain respectively. The resolution was more than 1.5. The regressive equation for eugenol was Y = 0. 106 4ρ - 1. 338 ( r = 0. 999 9 ), and the linear range was 77. 76 - 777. 6 μg · mL - 1, glycyrrhizic acid was Y = 0. 133 9p - 0. 222 0 ( r = 0. 999 9 ), and the linear range was 14. 40 ~ 144. 0 μg · mL - 1. The average recoveries of eugenol and glycyrrhizic acid were 99. 0% and 97. 3%, RSDs were 1.5% and 1.8%, respectively. CONCLUSION This method is simple,time-saving and accurate. It can be used for routine analysis of eugenol and glycyrrhizic acid in Bawei Tanxiang San.

  18. Studies on the effect of acid treated TiO{sub 2} on the electrical and tensile properties of hexanoyl chitosan-polystyrene-LiCF{sub 3}SO{sub 3} composite polymer electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Hanif, Nur Shazlinda Muhammad; Shahril, Nur Syuhada Mohd; Azmar, Amisha; Winie, Tan [Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam (Malaysia)

    2015-08-28

    Composite polymer electrolytes (CPEs) comprised of hexanoyl chitosan:polystyrene (90:10) blend, lithium triflouromethanesulfonate (LiCF{sub 3}SO{sub 3}) salt and titanium oxide (TiO{sub 2}) filler were prepared by solution casting technique. The TiO{sub 2} fillers were treated with 2% sulphuric acid (H{sub 2}SO{sub 4}) aqueous solution. The effect of acid treated TiO{sub 2} on the electrical and tensile properties of the electrolytes were investigated. Acid treated TiO{sub 2} decreased the electrolyte conductivity. Both the dielectric constant and dielectric loss decrease with increasing frequency and increases with increasing temperature. Relaxation times for ionic carriers were extracted from the loss tangent maximum peak at various temperatures. A distribution of relaxation time implied the non-Debye response. At all frequencies, ac conductivity increases with increasing temperature. An enhancement in the Young’s modulus was observed with the addition of TiO{sub 2}. The Young’s modulus increases with increasing TiO{sub 2} content. This is discussed using the percolation concept.

  19. Kinetics and Thermodynamics of Adsorption Glycyrrhizic Acid Triammonium Salt on NKA Macroporous Resin%NKA大孔吸附树脂对甘酸三铵盐吸附的动力学和热力学研究

    Institute of Scientific and Technical Information of China (English)

    何秀娟; 洪成林; 齐誉; 乔秀文; 但建明

    2013-01-01

    By static adsorption experiments,this paper studied the kinetics and adsorption thermodynamic characteristics of NKA macroporous resin in the process of adsorbing glycyrrhizic acid triammonium salt(GATS),and provided theoretical support for GATS macroporous adsorption resin separation and purification.Ultraviolet and visible spectrophotometry was used to detect the adsorptive kinetics curve and the adsorption equilibrium curve at different tenperatures.The adsorption kinetics behavior was well described by the pseudo-second-order kinetice equation.The thermodynamics behavior was correlated with Langmuir equation.In GATS adsorption process of NKA macroporous resin,enthalpy change ΔH and entropy change ΔS were positive,free energy change ΔG were negative,and adsorption activation energy was 36.01 kJ/mol when temperatures were in the range of 293~313 K.It is indicated that the adsorption was a spontaneous and endothermic process,the process of adsorption was mainly physical adsorption.%本文通过静态吸附实验,研究了NKA大孔吸附树脂吸附甘草酸三铵盐过程的吸附动力学和吸附热力学特征,以期为甘草酸大孔吸附树脂分离提纯提供理论支持.实验采用紫外可见分光光度法测定了吸附动力学曲线和不同温度时的吸附等温线,用拟二级动力学方程很好地描述了吸附动力学过程,使用Langmuir方程较好地拟合了等温吸附热力学过程.实验结果显示:NKA大孔吸附树脂对甘草酸三铵盐吸附焓变ΔH吸附和熵变ΔS吸附为正值,自由能变△G为负值,吸附活化能为Ea =36.01 kJ/mol;该吸附过程是自发的吸热过程,属于物理吸附范畴.

  20. Dynamic Changes of Ephedrine Hydrochloride, Pseudoephedrine Hydrochloride, Amygdalin and Glycyrrhizic Acid in Different Compatibility of San-Ao Decoction%三拗汤不同配伍煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸动态规律变化

    Institute of Scientific and Technical Information of China (English)

    张金花; 刘陶世; 程建明; 陈冬冬; 钱海峰

    2015-01-01

    目的:研究三拗汤在不同配伍煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸的动态规律变化.方法:采用高效液相色谱法(HPLC)同时测定三拗汤煎液中盐酸麻黄碱、盐酸伪麻黄碱、苦杏仁苷和甘草酸的转移率,选用Kromasil C18(4.6 mm×250 mm,5μm)色谱柱,以流动相甲醇-0.1%磷酸进行梯度洗脱,流速为1 mL·min-1,柱温30℃,进样量10μL.其中盐酸麻黄碱、盐酸伪麻黄碱和苦杏仁苷在208 nm波长下检测,甘草酸铵在250 nm波长下检测.结果:麻黄碱转移率在合煎液中大于分煎液,伪麻黄碱转移率在麻黄与苦杏仁配伍中最高,苦杏仁苷转移率在麻黄与苦杏仁配伍中最高,甘草酸转移率在合煎液中大于分煎液.结论:中药复方在煎煮过程中存在动态规律变化,应根据其变化有针对性提高药物的有效性和稳定性.%This paper was aimed to study the dynamic changes of San-Ao(SA) decoction in different compatibility of ephedrine hydrochloride,pseudoephedrine hydrochloride,amygdalin and glycyrrhizic acid.HPLC was used to simultaneously determinate the transfer rate of SA decoction of ephedrine hydrochloride,pseudoephedrine hydrochloride,amygdalin and glycyrrhizic acid.Kromasil C18 (4.6 mm×250 mm,5μm) column was selected with methanol and 0.1% phosphoric acid as a mobile phase to gradient.The flow rate was 1 mL·min-1.The column temperature was 30℃.The injection volume was 10μL.Ephedrine hydrochloride,pseudoephedrine hydrochloride and amygdalin were detected at the wavelength of 208 nm.The glycyrrhizic acid was detected at the wavelength of 250 nm.The results showed that the transfer rate of ephedrine hydrochloride in decoction was more than that of the single preparation.The transfer rate of pseudoephedrine hydrochloride was the highest in the combination of ephedra and bitter almond.The transfer rate of amygdalin was the highest in the combination of ephedra and bitter almond.The transfer rate of

  1. Comparison of alkaline phosphatase activity of MC3T3-E1 cells cultured on different Ti surfaces: modified sandblasted with large grit and acid-etched (MSLA), laser-treated, and laser and acid-treated Ti surfaces

    Science.gov (United States)

    Li, Lin-Jie; Kim, So-Nam

    2016-01-01

    PURPOSE In this study, the aim of this study was to evaluate the effect of implant surface treatment on cell differentiation of osteoblast cells. For this purpose, three surfaces were compared: (1) a modified SLA (MSLA: sand-blasted with large grit, acid-etched, and immersed in 0.9% NaCl), (2) a laser treatment (LT: laser treatment) titanium surface and (3) a laser and acid-treated (LAT: laser treatment, acid-etched) titanium surface. MATERIALS AND METHODS The MSLA surfaces were considered as the control group, and LT and LAT surfaces as test groups. Alkaline phosphatase expression (ALP) was used to quantify osteoblastic differentiation of MC3T3-E1 cell. Surface roughness was evaluated by a contact profilometer (URFPAK-SV; Mitutoyo, Kawasaki, Japan) and characterized by two parameters: mean roughness (Ra) and maximum peak-to-valley height (Rt). RESULTS Scanning electron microscope revealed that MSLA (control group) surface was not as rough as LT, LAT surface (test groups). Alkaline phosphatase expression, the measure of osteoblastic differentiation, and total ALP expression by surface-adherent cells were found to be highest at 21 days for all three surfaces tested (P.05). CONCLUSION This study suggested that MSLA and LAT surfaces exhibited more favorable environment for osteoblast differentiation when compared with LT surface, the results that are important for implant surface modification studies. PMID:27350860

  2. Cationic Ring Opening Polymerization of Octamethylcyclotetrasiloxane Initiated by Acid Treated Bentonite%酸白土催化体系开环八甲基环四硅氧烷的研究及机理探讨

    Institute of Scientific and Technical Information of China (English)

    陈碧; 詹晓力; 易玲敏; 陈丰秋

    2007-01-01

    Cationic ring opening polymerization of octamethylcyclotetrasiloxane (D4) initiated by acid treated bentonite was investigated. The experimental conditions were chosen on the basis of preliminary experiments.Higher temperature was found beneficial for the reaction process while stirring intensity beyond a certain level showed no obvious effect on the reaction rate. Polymers were characterized by Fourier transform infrared, proton nuclear magnetic resonance (1H-NMR) and gel permeation chromotography. The width of molecular mass distribution was found ranging between 1.2 and 1.4, which is extraordinarily narrow compared with that of cationic polymerizations reported elsewhere (>1.9). The results were believed due to the absence of free proton and counter ion which simplifies the polymerization process and the huge steric hindrance provided by bentonite particles which keeps the propagation of polysiloxane onto the surface of bentonite particles in a much more regular way. A feasible mechanism is proposed and seems to be supported well by experiments. Additionally, from the results of α,ω-dihydrogen terminated polysiloxanes prepared, the possibility of applying this potential environmentally friendly heterogeneous catalyst in industrial polymerization of cyclosiloxanes is anticipated.

  3. Effect of Compound Ammonium Glycyrrhizic S combined with Leigongtengduogan tablets in the treatment of eosinophil increases caused by chronic eczema%复方甘草酸单胺S联合雷公藤多甙治疗慢性湿疹引起嗜酸性粒细胞增多疗效观察

    Institute of Scientific and Technical Information of China (English)

    韩雪松; 岳致丰; 周向昭

    2011-01-01

    Objective To explore the effect of Compound Ammonium Glycyrrhizic S combined with Leigongtengduogan tablets in the treatment of eosinophil increases caused by chronic eczema. Methods The ECKMAN COULTER LH750 ANALYZER from the United States was used in analyzing the data. Patients were divided into treatment group with 30 patients applied with Compound Ammonium Glycyrrhizic S combined with Leigongtengduogan tablets and the control group with 30 patients applied with the Citirizine Dihydrochloride Capsules combined with Ketotifen Fumarate Tablets. Before and after the treatment, the blood of eosinophil, self - perceived symptoms, and skin damage changes were recorded and compared. Results After 4- week treatment,the recovery and efficiency rate of the eosinophils decline index in the treatment group were 43.33 %and 96.66 % respectively, which were significantly higher than those in the control group, 3.33 %and 30.00 %. The recovery and efficiency rate of TSS decline index in the treatment group were 37.67 % and 93.34 %, which were significantly higher than those in the control group, 6.67 % and 26.67 %. It is statistically different (P < 0.01). Conclusion Compound Ammonium Glycyrrhizic S combined with Leigongtengduogan tablets can effectively promote eosinophil count drops. Clinical symptoms and physical signs significantly improve.%目的 观察复方甘草酸单胺S联合雷公藤多甙治疗慢性湿疹引起嗜酸性粒细胞增多的临床疗效.方法 采用5分类血细胞分析仪分别对治疗组30例(应用复方甘草酸单胺S联合雷公藤多甙)和对照组30例(应用盐酸西替利嗪胶囊联合富马酸酮替芬)在治疗前后对外周血嗜酸粒细胞计数进行测定,同时记录自觉症状和皮损情况的改善,并对比分析.结果 治疗4周后,治疗组嗜酸性粒细胞下降指数的痊愈率及有效率分别为43.33%、96.66%,明显高于对照组的3.33%、30.00%;治疗组TSS下降指数的痊

  4. 18α、18β-甘草酸及其不同配比物对CCl4肝损伤大鼠的影响%Influence of 18α-,18β-Glycyrrhizic Acids and their Different Proportions on CCl4 Hepatotoxicity in Rats

    Institute of Scientific and Technical Information of China (English)

    茹仁萍; 尤琳雅; 陈晓瑾

    2011-01-01

    Objective: To study the protective function and select the optimal formulation of 18α-, 18β -glycyrrhizic acid and their different proportions against CCl4induced hepatotoxicity in rats. Methods:Healthy SD male rats, weighting (200 ± 20) g, 10 per group were randomized into 7 groups: control group, CCl4 - injured group, 18α - glycyrrhizic acid group, 18β - glycyrrhizic acid group and their proportions of 4∶ 6, 3∶ 7, 2∶ 8 groups. 6% CCl4 was given to rats by intraperitoneal (ip) injection, with the exception of control group. The rats were killed 24 h and 48h after CCl4 injury respectively. Serum alanine amiotransferase (ALT) ,aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities were determined; the liver and spleen weights of each rat as well as superoxide dismutase (SOD) activity in the liver homogenate were also detected. The liver pathological examination was also judged. Results :The acute CCl4 - injured model was successfully established due to increased serum enzyme level, swollen liver, atrophied spleen, decreased SOD activity and change in liver pathological examination Among the five formulations, the 3∶7 group did best in inhibiting the increases of serum ALT, AST and liver index, preventing the decreases of spleen index and SOD activity, and alleviating the lesion in liver cell obviously. Conclusion: In all, the formulation of 3∶ 7 showed the most potent liver protection against CCl4 - induced hepatotoxicity.%目的:研究不同配比的18α、18β-甘草酸(GL)对四氯化碳(CCl4)肝损伤大鼠的保护作用,探讨临床应用合理比例.方法取健康雄性SD大鼠(200±20)g 70只,随机分为7组,即正常组、CCl4肝损伤组、18α-GL、18β-GL和3个不同配比组(α:β比例分别为4:6、3:7和2:8).采用腹腔注射CCl4复制大鼠急性肝损伤模型.分别于24h和48h后摘眼球取血,测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)活性,同时测定肝脾重量,

  5. 甘草酸对酸性环境中变异链球菌生长影响的体外研究%Effect of glycyrrhizic acid on growth of Streptococcus mutans under acid environment in vitro

    Institute of Scientific and Technical Information of China (English)

    张凌楠; 何永红; 张菲菲; 田婷玉; 宋伟; 万呼春

    2012-01-01

    目的 研究酸性环境中甘草酸对体外培养变异链球菌生长的影响.方法 在pH 7.0、pH 5.5和pH 4.0环境中培养变异链球菌,同时在培养基中加入3种浓度(0.78、1.57、3.13 mg·mL-1)的甘草酸,37℃下厌氧培养24h后,测定各组的菌落计数和菌悬液吸光度值,分别以阴性对照组和pH 7.0组细菌生存率为对照,计算各组细菌的生存率.结果 以阴性对照组为对照,0.78、1.57和3.13 mg·mL-1甘草酸组在pH 5.5环境时细菌生存率为60.96%、60.27%和45.58%,在pH 4.0时细菌生存率为68.75%、53.12%和45.83%.以pH 7.0组为对照,0.78、1.57和3.13 mg·mL-1甘草酸组在pH 5.5和pH 4.0时细菌生存率分别为52.25%和39.05%、74.39%和43.11%、86.38%和55.30%.结论 在酸性环境中,甘草酸能够抑制体外变异链球菌的生长,环境酸度降低可使甘草酸的抑菌作用增强.%Objective To investigate the antibacterial activity of glycyrrhizic acid (GA) against Streptococcus mutans (S. mutans) under acidic environment in vitro. Methods Working culture were prepared by inoculation of S. mutans into TPY broth followed by static incubation under anaerobic condition at 37 ℃ for 24 h. TPY broth was supplemented with three kinds density of GA(0.78, 1.57, 3.13mg·mL-1), whose acidity was regulated to pH7.0, pH5.5 and pH4.0. And the group of pH 7.0 was used as negative control. The growth of S. mutans was measured by A600 of bacteria suspension and counting colony forming unit (CFU). In addition, the survival rate of S. mutans was calculated. Results In pH5.5 groups, the survival rates of 0.78, 1.57 and 3.13 mg·mL-1 GA groups were 60.96%, 60.27% and 45.58%, respectively, and in pH4.0 groups, the survival rates were 68.75%, 53.12% and 45.83%. In 0.78, 1.57 and 3.13 mg·mL-1 GA groups, the survival rates of pH5.5 and pH4.0 were 52.25% and 39.05%, 74.39% and 43.11%, 86.38% and 55.30%, respectively. Conclusion GA could inhibit the growth of S. mutans under

  6. 18α-甘草酸固体脂质纳米粒抗大鼠急性肝损伤作用研究%Protective Effect of 18a-Glycyrrhizic Acid Solid Lipid Nanoparticles on Acute Liver Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    王维; 潘旭旺; 邵益丹; 席建军; 庄让笑

    2014-01-01

    目的 研究18α-甘草酸固体脂质纳米粒(18α-glycyrrhizic acid solid lipid nanoparticles,18α-GL-SLN)的抗大鼠急性肝损伤作用.方法 用CC14致大鼠急性肝损伤,以生化指标和病理变化评价18α-GL-SLN的抗肝损伤作用.结果 与模型组比较,18α-GL-SLN各剂量组和18α-GL组ALT、AST、TBil、γ-GT、ALP水平明显降低,差异有统计学意义(P<0.05),提示对大鼠急性肝损伤均有一定的治疗作用,尤其是18α-GL-SLN中、高剂量组,效果优于18α-GL组(P<0.05);病理切片显示各给药组肝组织损伤明显减轻.结论 18α-GL-SLN有抗CC14致大鼠急性肝损伤作用,并且其作用优于18α-GL.

  7. Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents.

    Science.gov (United States)

    Mrđanović, Jasminka; Jungić, Saša; Šolajić, Slavica; Bogdanović, Višnja; Jurišić, Vladimir

    2012-08-01

    The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p<0.05; MN, p<0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p<0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se contributed to the decreasing of genome damages in workers handling the cytostatics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions

    NARCIS (Netherlands)

    Blanquet, S.; Zeijdner, E.; Beyssac, E.; Meunier, J.-P.; Denis, S.; Havenaar, R.; Alric, M.

    2004-01-01

    Purpose. The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. Methods. Two mode

  9. Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine.

    Science.gov (United States)

    Fennell, Timothy R; Mortensen, Ninell P; Black, Sherry R; Snyder, Rodney W; Levine, Keith E; Poitras, Eric; Harrington, James M; Wingard, Christopher J; Holland, Nathan A; Pathmasiri, Wimal; Sumner, Susan C J

    2017-05-01

    Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg(-1) ) or by gavage (p.o.) (10 mg kg(-1) ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (μg Ag g(-1) tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Effects of Orally Administered Lactoferrin and Lactoperoxidase-Containing Tablets on Clinical and Bacteriological Profiles in Chronic Periodontitis Patients

    Directory of Open Access Journals (Sweden)

    Eiju Shimizu

    2011-01-01

    Full Text Available This study was undertaken to evaluate the effect of oral administration of lactoferrin (LF and lactoperoxidase-(LPO-containing tablet on periodontal condition. Seventy-two individuals with chronic periodontitis were randomly assigned to take either bovine LF and LPO-containing tablets (test group, n=37 or control tablets (control group, n=35 every day for 12 weeks. Periodontal parameters and levels of subgingival plaque bacteria, human and bovine LF, and endotoxin in gingival crevicular fluid (GCF were evaluated at baseline, 1 week, 4 weeks, and 12 weeks. Significant differences were observed in GCF levels of bovine LF between the test and control groups throughout the study (P<.05. However, clinical and bacteriological parameter values proved comparable between the two groups at 1 week to 12 weeks. Therefore, the effect of oral administration of LF and LPO-containing tablets might be weak on periodontal and bacteriological profile in this study.

  11. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    Science.gov (United States)

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

  12. Attenuation of obesity-induced inflammation in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Science.gov (United States)

    Hirose, Shouhei; Asano, Krisana; Nakane, Akio

    2017-03-11

    Obesity is associated with chronic inflammation of adipose tissue and causes development of type 2 diabetes. M1 macrophage population was increased in adipose tissue of obese mouse. M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in various mouse inflammatory diseases. In this study, we examined the effect of PG on type 2 diabetes using high-fat-diet (HFD) induced obese mouse model. Oral PG administration enhanced the population of small adipocytes (area less than 1000 μm(2)) without body and tissue weight gain. In addition, PG administration suppressed mRNA expression of TNF-α, IL-6 and CXCL2 in adipose tissue. The proportion of M1 macrophages was decreased by PG administration. In addition, PG administration suppressed hyperglycemia after intraperitoneal glucose injection. Fasted serum insulin level was decreased in PG-administered mice. Moreover, insulin-stimulated phosphorylation of Akt was enhanced in the liver and gastrocnemius skeletal muscle of PG-administered mice. These data suggested that PG administration improves hyperglycemia and insulin sensitivity in obese mice by modulation of M1 macrophages which secrete proinflammatory cytokines in adipose tissue and activation of Akt in liver and skeletal muscle.

  13. Simultaneous determination of three polyphenols in rat plasma after orally administering hawthorn leaves extract by the HPLC method.

    Science.gov (United States)

    Ying, Xixiang; Meng, Xiansheng; Wang, Siyuan; Wang, Dong; Li, Haibo; Wang, Bing; Du, Yang; Liu, Xun; Zhang, Wenjie; Kang, Tingguo

    2012-01-01

    A simple and sensitive HPLC method was developed to simultaneously determine three active compounds, vitexin-4″-O-glucoside (VG), vitexin-2″-O-rhamnoside (VR) and hyperoside (HP), in rat plasma after administering the hawthorn leaves extract (HLE). An HPLC assay with baicalin as the internal standard was carried out using a Phenomsil C₁₈ analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6 : 1.5 : 18.5 : 74, v/v/v/v). The calibration curves were linear over the range of 2.5-500, 0.2-25 and 0.25-12.5 µg mL⁻¹ for VG, VR and HP, respectively. The method was reproducible and reliable, with relative standard deviations of the intra- and inter-day precision between 1.2% and 13.2% for the analysis of the three analytes. The validated HPLC method herein described was successfully applied to the pharmacokinetic study of VG, VR and HP after oral administration of HLE to rats over the dose range of 2.5-10  mL kg⁻¹.

  14. Anti-tumor properties of orally administered glucosamine and N-acetyl-D-glucosamine oligomers in a mouse model.

    Science.gov (United States)

    Masuda, Sachie; Azuma, Kazuo; Kurozumi, Seiji; Kiyose, Masatoshi; Osaki, Tomohiro; Tsuka, Takeshi; Itoh, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Sato, Kimihiko; Okamoto, Yoshiharu

    2014-10-13

    The current study evaluated the anti-tumor activities of N-acetyl-d-glucosamine oligomer (NACOS) and glucosamine oligomer (COS) after their oral administration in a tumor (colon 26)-bearing mouse model. Compared to the control group, NACOS and COS groups showed significantly suppressed tumor growth, and apparent, marked apoptosis in tumor tissues. Furthermore, serum interleukin-12p70 and interferon-γ levels significantly increased in the NACOS and COS groups compared to the corresponding levels in the control group. Collectively, the results indicate the oral administration of NACOS and COS could enhance innate immunity. Results of experiments in Myd-88 knockout mice revealed that the apparent effects were related to both Myd-88-dependent and Myd-88-independent pathways. The data indicated that oral administration of NACOS and COS produced anti-tumor effects through the induction of apoptosis and stimulation of the immune system, which suggests that NACOS and COS are candidate anti-tumor functional foods.

  15. Anti-inflammatory effects of orally administered glucosamine oligomer in an experimental model of inflammatory bowel disease.

    Science.gov (United States)

    Azuma, Kazuo; Osaki, Tomohiro; Kurozumi, Seiji; Kiyose, Masatoshi; Tsuka, Takeshi; Murahata, Yusuke; Imagawa, Tomohiro; Itoh, Norihiko; Minami, Saburo; Sato, Kimihiko; Okamoto, Yoshiharu

    2015-01-22

    Anti-inflammatory effects of oral administration of the glucosamine oligomers (chito-oligosaccharides: COS) were evaluated in an experimental model of inflammatory bowel disease (IBD). Oral administration of COS improved shortening of colon length and tissue injury (as assessed by histology) in mice. Oral administration of COS inhibited inflammation in the colonic mucosa by suppression of myeloperoxidase activation in inflammatory cells, as well as activation of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase. Oral administration of COS also reduced serum levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6). Moreover, it prolonged survival time in mice. These data suggest that COS have anti-inflammatory effects in an experimental model of IBD, and could be new functional foods for IBD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.

    Science.gov (United States)

    Wilson, James P; Cobb, Ronald R; Dungan, Nathanael W; Matthews, Laura L; Eppler, Bärbel; Aiello, Kenneth V; Curtis, Shiro; Boger, Teannetta; Guilmette, Raymond A; Weber, Waylon; Doyle-Eisele, Melanie; Talton, James D

    2015-03-01

    Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.

  17. Metabolism of orally administered (/sup 3/H)ergocalciferol and (/sup 3/H)cholecalciferol by dairy calves

    Energy Technology Data Exchange (ETDEWEB)

    Sommerfeldt, J.L.; Napoli, J.L.; Littledike, E.T.; Beitz, D.C.; Horst, R.L.

    1983-12-01

    Concentrations of ergocalciferol, cholecalciferol, and their metabolites in plasma were determined after a single oral dose of (/sup 3/H)ergocalciferol or (/sup 3/H)cholecalciferol was given to 95- to 105-kg Jersey bull calves. One group (three calves) was given 365 muCi of (/sup 3/H)ergocalciferol (1.2 Ci/mmol) per calf, and the other group (three calves) was given 365 muCi of (/sup 3/H)cholecalciferol (1.2 Ci/mmol) per calf. Fourteen blood samples were taken from each calf during the 3 weeks after administration. Total plasma radioactivity was highest at 80 hours in both groups (8400 dpm/ml and 4600 dpm/ml in the (/sup 3/H)cholecalciferol- and (/sup 3/H)ergocalciferol-treated calves, respectively). For determination of the time-dependent appearance and disappearance of plasma vitamin D and vitamin D metabolites, the plasma /sup 3/H-labeled steroids were extracted and separated by high-performance liquid chromatography. In both groups, (/sup 3/H)vitamin D peaked at 24-48 hours and was the predominant radioactive form in plasma 10-15 hours after dosing. After 15 hours, 25-(/sup 3/H)hydroxyvitamin D became the predominant labeled metabolite, reaching its maximal concentration between 48 and 96 hours. Concentrations of 25-(/sup 3/H)hydroxycholecalciferol were about twice those of 25-(/sup 3/H)hydroxyergocalciferol. The appearance/disappearance profile of 25,26-(/sup 3/H)dihydroxycholecalciferol and 1,25(/sup 3/H)hydroxycholecalciferol resembled that of 25-(/sup 3/H)hydroxycholecalciferol.

  18. Gastric emptying of orally administered glucose solutions and incretin hormone responses are unaffected by laparoscopic adjustable gastric banding

    DEFF Research Database (Denmark)

    Usinger, Lotte; Hansen, Katrine B; Kristiansen, Viggo B

    2011-01-01

    Laparoscopic adjustable gastric banding (LAGB) provides weight loss in obese individuals and is associated with improved glucose homeostasis and resolution of type 2 diabetes. However, in most available reports, potentially inappropriate methodology has been applied when measuring the impact...

  19. Effect of orally administered collagen hydrolysate on gene expression profiles in mouse skin: a DNA microarray analysis.

    Science.gov (United States)

    Oba, Chisato; Ito, Kyoko; Ichikawa, Satomi; Morifuji, Masashi; Nakai, Yuji; Ishijima, Tomoko; Abe, Keiko; Kawahata, Keiko

    2015-08-01

    Dietary collagen hydrolysate has been hypothesized to improve skin barrier function. To investigate the effect of long-term collagen hydrolysate administration on the skin, we evaluated stratum corneum water content and skin elasticity in intrinsically aged mice. Female hairless mice were fed a control diet or a collagen hydrolysate-containing diet for 12 wk. Stratum corneum water content and skin elasticity were gradually decreased in chronologically aged control mice. Intake of collagen hydrolysate significantly suppressed such changes. Moreover, we used DNA microarrays to analyze gene expression in the skin of mice that had been administered collagen hydrolysate. Twelve weeks after the start of collagen intake, no significant differences appeared in the gene expression profile compared with the control group. However, 1 wk after administration, 135 genes were upregulated and 448 genes were downregulated in the collagen group. This suggests that gene changes preceded changes of barrier function and elasticity. We focused on several genes correlated with functional changes in the skin. Gene Ontology terms related to epidermal cell development were significantly enriched in upregulated genes. These skin function-related genes had properties that facilitate epidermal production and differentiation while suppressing dermal degradation. In conclusion, our results suggest that altered gene expression at the early stages after collagen administration affects skin barrier function and mechanical properties. Long-term oral intake of collagen hydrolysate improves skin dysfunction by regulating genes related to production and maintenance of skin tissue.

  20. Bioequivalence in dogs of a meloxicam formulation administered as a transmucosal oral mist with an orally administered pioneer suspension product.

    Science.gov (United States)

    Lees, P; Cheng, Z; Keefe, T J; Weich, E; Bryd, J; Cedergren, R; Cozzi, E

    2013-02-01

    A mucosal mist formulation of meloxicam, administered as a spray into the mouth (test article), was compared for bioequivalence to a pioneer meloxicam suspension for oral administration (reference article). Pharmacokinetic profiles and average bioequivalence were investigated in 20 dogs. The study design comprised a two-period, two-sequence, two-treatment cross-over design, with maximum concentration (C(max)) and area under plasma concentration-time curve to last sampling time (AUC(last)) used as pivotal bioequivalence variables. Bioequivalence of the products was confirmed, based on relative ratios of geometric mean concentrations (and 90% confidence intervals within the range 0.80-1.25) for C(max) of 101.9 (97.99-106.0) and for AUC(last) of 97.24 (94.44-100.1). The initial absorption of meloxicam was more rapid for the test article, despite virtually identical C(max) values for the two products. Mean elimination half-lives were 29.6 h (test article) and 30.0 h (reference article). The meloxicam plasma concentration-time profiles were considered in relation to published data on the inhibition of the cyclooxygenase-1 (COX-1) and COX-2 isoenzymes by meloxicam.

  1. Bacterial antigen expression is an important component in inducing an immune response to orally administered Salmonella-delivered DNA vaccines.

    Directory of Open Access Journals (Sweden)

    Michelle E Gahan

    Full Text Available BACKGROUND: The use of Salmonella to deliver heterologous antigens from DNA vaccines is a well-accepted extension of the success of oral Salmonella vaccines in animal models. Attenuated S. typhimurium and S. typhi strains are safe and efficacious, and their use to deliver DNA vaccines combines the advantages of both vaccine approaches, while complementing the limitations of each technology. An important aspect of the basic biology of the Salmonella/DNA vaccine platform is the relative contributions of prokaryotic and eukaryotic expression in production of the vaccine antigen. Gene expression in DNA vaccines is commonly under the control of the eukaryotic cytomegalovirus (CMV promoter. The aim of this study was to identify and disable putative bacterial promoters within the CMV promoter and evaluate the immunogenicity of the resulting DNA vaccine delivered orally by S. typhimurium. METHODOLOGY/PRINCIPAL FINDINGS: The results reported here clearly demonstrate the presence of bacterial promoters within the CMV promoter. These promoters have homology to the bacterial consensus sequence and functional activity. To disable prokaryotic expression from the CMV promoter a series of genetic manipulations were performed to remove the two major bacterial promoters and add a bacteria transcription terminator downstream of the CMV promoter. S. typhimurium was used to immunise BALB/c mice orally with a DNA vaccine encoding the C-fragment of tetanus toxin (TT under control of the original or the modified CMV promoter. Although both promoters functioned equally well in eukaryotic cells, as indicated by equivalent immune responses following intramuscular delivery, only the original CMV promoter was able to induce an anti-TT specific response following oral delivery by S. typhimurium. CONCLUSIONS: These findings suggest that prokaryotic expression of the antigen and co-delivery of this protein by Salmonella are at least partially responsible for the successful oral delivery of C-fragment DNA vaccines containing the CMV promoter by S. typhimurium.

  2. Orally administered P22 phage tailspike protein reduces salmonella colonization in chickens: prospects of a novel therapy against bacterial infections.

    Directory of Open Access Journals (Sweden)

    Shakeeba Waseh

    Full Text Available One of the major causes of morbidity and mortality in man and economically important animals is bacterial infections of the gastrointestinal (GI tract. The emergence of difficult-to-treat infections, primarily caused by antibiotic resistant bacteria, demands for alternatives to antibiotic therapy. Currently, one of the emerging therapeutic alternatives is the use of lytic bacteriophages. In an effort to exploit the target specificity and therapeutic potential of bacteriophages, we examined the utility of bacteriophage tailspike proteins (Tsps. Among the best-characterized Tsps is that from the Podoviridae P22 bacteriophage, which recognizes the lipopolysaccharides of Salmonella enterica serovar Typhimurium. In this study, we utilized a truncated, functionally equivalent version of the P22 tailspike protein, P22sTsp, as a prototype to demonstrate the therapeutic potential of Tsps in the GI tract of chickens. Bacterial agglutination assays showed that P22sTsp was capable of agglutinating S. Typhimurium at levels similar to antibodies and incubating the Tsp with chicken GI fluids showed no proteolytic activity against the Tsp. Testing P22sTsp against the three major GI proteases showed that P22sTsp was resistant to trypsin and partially to chymotrypsin, but sensitive to pepsin. However, in formulated form for oral administration, P22sTsp was resistant to all three proteases. When administered orally to chickens, P22sTsp significantly reduced Salmonella colonization in the gut and its further penetration into internal organs. In in vitro assays, P22sTsp effectively retarded Salmonella motility, a factor implicated in bacterial colonization and invasion, suggesting that the in vivo decolonization ability of P22sTsp may, at least in part, be due to its ability to interfere with motility… Our findings show promise in terms of opening novel Tsp-based oral therapeutic approaches against bacterial infections in production animals and potentially in humans.

  3. International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

    Science.gov (United States)

    Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

    2013-10-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

  4. International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products: A Survey of Similarities and Differences

    OpenAIRE

    Davit, Barbara; Braddy, April C.; Conner, Dale P.; Yu, Lawrence X.

    2013-01-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Assoc...

  5. The effects of orally administered Bacillus coagulans and inulin on prevention and progression of rheumatoid arthritis in rats

    Directory of Open Access Journals (Sweden)

    Khadijeh Abhari

    2016-07-01

    Full Text Available Background: Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. Objective: In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA, using arthritis-induced rat model. Design: Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1 control: normal healthy rats fed with standard diet, 2 disease control (RA: arthritis-induced rats fed with standard diet, 3 prebiotic (PRE: RA+ 5% w/w long-chain inulin, 4 probiotic (PRO: RA+ 109 spores/day B. coagulans by orogastric gavage, 5 synbiotic (SYN: RA+ 5% w/w long-chain inulin and 109 spores/day B. coagulans, and 6 treatment control: (INDO: RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn, serum amyloid A (SAA, and TNF-α and alpha-1-acid glycoprotein (α1 AGp was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction, respectively. Results: Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001. A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001, which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1 AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001. Conclusion: The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.

  6. Effect of orally administered L. fermentum NCIMB 5221 on markers of metabolic syndrome: an in vivo analysis using ZDF rats.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Jones, Mitchell L; Labbé, Alain; Rodes, Laetitia; Kahouli, Imen; Prakash, Satya

    2014-01-01

    Metabolic syndrome, encompassing type 2 diabetes mellitus and cardiovascular disease, is a growing health concern of industrialized countries. Ferulic acid (FA) is a phenolic acid found in foods normally consumed by humans that has demonstrated antioxidant activity, cholesterol-lowering capabilities, and anti-tumorigenic properties. Select probiotic bacteria, including Lactobacillus fermentum NCIMB 5221, produce FA due to intrinsic ferulic acid esterase activity. The aim of the present research was to investigate a FA-producing probiotic, L. fermentum NCIMB 5221, as a biotherapeutic for metabolic syndrome. The probiotic formulation was administered daily for 8 weeks to Zucker diabetic fatty (ZDF) rats, a model of hyperlipidemia and hyperglycemia. Results show that the probiotic formulation reduced fasting insulin levels and insulin resistance, significantly reduced serum triglycerides (p = 0.016), lowered serum low-density lipoprotein cholesterol levels (p = 0.008), and significantly reduced the atherogenic (p = 0.016) and atherosclerosis (p = 0.012) index as compared to the control animals. In addition, the probiotic formulation significantly increased high-density lipoprotein cholesterol levels (p = 0.041) as compared to the control animals. This research indicates that administration of the FA-producing L. fermentum NCIMB 5221 has the potential to reduce insulin resistance, hyperinsulinemia, hypercholesterolemia, and other markers involved in the pathogenesis of metabolic syndrome. Further studies are required to investigate the human clinical potential of the probiotic formulation in affecting the markers and pathogenesis of metabolic syndrome.

  7. Differences in the Neuroprotective Effect of Orally Administered Virgin Olive Oil (Olea europaea) Polyphenols Tyrosol and Hydroxytyrosol in Rats.

    Science.gov (United States)

    De La Cruz, José Pedro; Ruiz-Moreno, Maria Isabel; Guerrero, Ana; Reyes, José Julio; Benitez-Guerrero, Adela; Espartero, José Luis; González-Correa, José Antonio

    2015-07-01

    The neuroprotective effect of virgin olive oil (VOO) polyphenols has been related to their antioxidant effect. The main objective was to analyze how tyrosol and hydroxytyrosol contribute to the antioxidant and neuroprotective effects of VOO in a model of hypoxia-reoxygenation in rat brain slices. Rats were treated per os (po) (10 or 20 mg/kg/day) with hydroxytyrosol ethyl ether (HTEE), tyrosol ethyl ether (TEE), or 3,4-di-o-methylidene-hydroxytyrosol ethyl ether (MHTEE), used as a negative control for antioxidant effects. Lipid peroxidation was inhibited with HTEE, TEE, and MHTEE (from 5.0 ± 1.5 to 2.6 ± 1.5, 4.5 ± 1.5, and 4.8 ± 1.5 nmol/mg protein, respectively). However, all three compounds had similar neuroprotective effects: from 2.8 ± 0.07 to 1.8 ± 0.02 arbitrary units for HTEE, 1.4 ± 0.09 arbitrary units for TEE, and 1.3 ± 0.2 arbitrary units for MHTEE. All three compounds inhibited 3-nitrotyrosine production (from 3.7 ± 0.3 to 1.2 ± 0.03 nmol/0.1 g tissue for HTEE, 1.0 ± 0.2 nmol/0.1 g tissue for TEE, and 1.3 ± 0.1 nmol/0.1 g tissue for MHTEE), prostaglandin E2 production (from 55.7 ± 2.2 to 46.4 ± 1.9 pg/0.1 g tissue for HTEE, 24.7 ± 1.3 pg/0.1 g tissue for TEE, and 27.6 ± 2.6 pg/0.1 g tissue for MHTEE), whereas only HTEE inhibited IL1β production (from 35.7 ± 1.5 to 21.6 ± 0.8 pg/0.1 g tissue). Pearson correlation coefficients related neuroprotective effect with an antioxidant effect for HTEE (R = 0.72, p < 0.001), and inhibition of nitrosative stress (R = 0.78, 0.67, and 0.66 for HTEE, TEE, and MHTEE, respectively, p < 0.001) and inflammatory mediators (R = 0.72, 0.79, and 0.64 for HTEE, TEE, and MHTEE, respectively, p < 0.001) with all three compounds.

  8. Effect of orally administered soy milk fermented with Lactobacillus plantarum LAB12 and physical exercise on murine immune responses.

    Science.gov (United States)

    Appukutty, M; Ramasamy, K; Rajan, S; Vellasamy, S; Ramasamy, R; Radhakrishnan, A K

    2015-01-01

    Probiotics are live microorganisms that confer health benefits through the gastrointestinal microbiota. This nutritional supplement may benefit athletes who undergo rigorous training by maintaining their gastrointestinal functions and overall health. In this study the influence of moderate physical exercise using a graded treadmill exercise, alone or in combination with the consumption of a soy product fermented with Lactobacillus plantarum LAB12 (LAB12), on tumour necrosis factor alpha (TNF-α) responses was investigated in a murine model. Male BALB/c mice were randomly divided into four groups of six mice each (control, exercise alone, LAB12 and LAB12 + exercise). Mice treated with the potential probiotic LAB12 were orally gavaged for 42 days. At autopsy, blood and spleen from the animals were collected. The splenocytes were cultured in the presence of a mitogen, concanavalin A (Con A). The amount of TNF-α produced by the Con A-stimulated splenocytes was quantified using ELISA, while their proliferation was determined using the [(3)H]-thymidine incorporation method. This study shows that LAB12-supplemented and exercise-induced mice showed marked increase (P<0.05) in cell proliferation compared to the control animals. TNF-α production was suppressed (P<0.05) in the LAB12 group compared to the untreated mice. These results demonstrate that supplementation with LAB12 has immunomodulatory effects, under conditions of moderate physical exercise, which may have implications for human athletes. Further investigation in human trials is warranted to confirm and extrapolate these findings.

  9. 氧化钛涂层及改性后氧化钛涂层的细胞相容性研究%Research of the effects of cellular biocompatibility of plasma sprayed titanium dioxide coating and acid-treated titanium dioxide coating

    Institute of Scientific and Technical Information of China (English)

    孟德强; 曾庆敏; 熊敏

    2011-01-01

    [ Objective] To study the cellular compatibility and bioactivity of plasma sprayed titanium dioxide coating and acid- treated titanium dioxide coating. [ Methods ] Titanium dioxide was coated on Ti -6Al -4V by plasma spraying methods. The coating surface of one group was treated with acid, and the other group was not treated. Human osteoblasts were cultured on the coat with the density of 4 000/cm2. At 1, 4, 7 days the growth of the osteoblasts was examined with the method of MTS,and the shape and quantity of the osteoblasts on the titanium dioxide coating were observed by scaning electronic microscopy.[Results] The growth speed of human osteoblasts on acid - treated titanium dioxide coating was higher than that on titanium dioxide coating. The shape and quantity of human osteoblasts on acid - treated titanium dioxide coating were better than that on titanium dioxide coating. [ Conclusion] The cellular compatibility of acid - treated titanium dioxide coating is better than that of titanium dioxide coating.%[目的]研究氧化钛涂层及改性后氧化钛涂层的细胞相容性和生物活性.[方法]使用等离子喷涂法将氧化钛涂布于 Ti-6Al-4V 表面,一组涂层表面经过酸处理,另一组不作处理,将人成骨细胞按照 4 000个/cm2 定量接种于涂层表面,分别于1、4、7 d 用 MTS 法测定涂层表面细胞增殖情况,并用扫描电镜观察涂层表面成骨细胞形态及数量.[结果]经酸处理氧化钛涂层组的细胞增殖速率明显高于未经处理组,涂层表面细胞形态优于未经处理组.[结论]经酸处理改性后的氧化钛涂层的细胞相容性比未改性的氧化钛涂层有所提高.

  10. Ultra-thin Al{sub 2}O{sub 3} coating on the acid-treated 0.3Li{sub 2}MnO{sub 3}⋅0.7LiMn{sub 0.60}Ni{sub 0.25}Co{sub 0.15}O{sub 2} electrode for Li-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Mansoo [Battery Research Center, Korea Electrotechnology Research Institute, Changwon 642-120 (Korea, Republic of); Dept. of Energy Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Ham, Giyul [Dept. of Materials and Science Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Jin, Bong-Soo; Lee, Sang-Min [Battery Research Center, Korea Electrotechnology Research Institute, Changwon 642-120 (Korea, Republic of); Lee, Young Moo [Dept. of Energy Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Wang, Guoxiu [Centre for Clean Energy Technology, School of Chemistry and Forensic Science, University of Technology, Sydney, NSW 2007 (Australia); Kim, Hyun-Soo, E-mail: hskim@keri.re.kr [Battery Research Center, Korea Electrotechnology Research Institute, Changwon 642-120 (Korea, Republic of)

    2014-09-01

    Highlights: • 0.3Li{sub 2}MnO{sub 3}⋅0.7LiMn{sub 0.60}Ni{sub 0.25}Co{sub 0.15}O{sub 2} composites were preconditioned by HNO{sub 3}. • The alumina thin film was directly coated on the electrode by an atomic layer deposition. • The acid-treated samples showed significantly higher discharge capacity. • The alumina-coated electrode showed the improved capacity retention ratio. - Abstract: The Li and Mn-rich layered composites represented by Li{sub 2}MnO{sub 3}–LiMO{sub 2} has been attracting great interests owing to its exceptional high capacity (⩾250 mA h g{sup −1}) and enhanced structural stability. In order to improve the initial coulombic efficiency and cyclability of the composites, the material has been activated by an acid-treatment and coated with an Al{sub 2}O{sub 3} using an atomic layer deposition (ALD). The acid-treated electrode showed a higher discharge capacity than the as-prepared electrode. The alumina-coated electrode provided an improved specific capacity of the electrode but also cycling stability, when compared with the bare electrode. The electrode coated with the alumina could lead to a decrease in undesirable reactions, thereby acting as a stable protecting layer that could quickly transport Li{sup +} ions during charge and discharge process.

  11. EFFECTS OF 18α-GLYCYRRHIZIC ACID ON RAT LIVER CYTOCHROME P450 ISOENZYMES AND PHASE II TRANSFERASE%18α-甘草酸二铵对大鼠肝脏细胞色素P450和II相酶的影响

    Institute of Scientific and Technical Information of China (English)

    杨静; 彭仁; 孔锐; 于皆平

    2001-01-01

    AIM To study the effect of 18α-glycyrrhizic acid (18α-GL) on hepatic microsomal drug metabolizing enzymes in rats. METHODS 18α-GL (12.5, 50.0 mg*kg-1*d-1) were given ip to male Wistar rats for 3, 6 or 12 consecutive days. The rats were sacrificed 24 h after the last dose and the liver microsomes were prepared for analysis of cytochrome P450 (CYP) isozymes and phase II transferase activites. RESULTS Aniline hydroxylase (CYP2E1) activities in the rats treated with 18α-GL (12.5, 50.0 mg*kg-1) for 6 days decreased dose-dependently by up to 53.2%; For 3, 6 or 12 days 7-ethoxyresorufin O-deethylase (CYP1A1) activities in the rats of 50 mg*kg-1 dose group decreased time-dependently by 17.6%, 38.3% and 47.3%, respectively; Erythromycin N-demethylase (CYP3A) activities was significantly inhibited from 23.1% to 34.3%. UDP-glucuronosyltransferase activities toward 7-hydroxy-4-methylcoumarin significantly increased ranging from 19.3% to 29.9%. UDP-glucuronosyltransferase activities toward 4-phenylphenol in the rats treated with 18α-GL (12.5, 50.0 mg*kg-1) for 6 days increased by 45.9% and 70.3%. Glutathione S-transferase (GST) activities in the rats treated with 18α-GL (12.5,50.0 mg*kg-1) for 6 days increased by 13.7% and 48.3% in dose-dependent manner. CONCLUSION 18α-GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.%目的研究18α-甘草酸二铵(18α-GL)对肝脏药物代谢酶的影响。方法♂ Wistar大鼠ig 18α-GL 12.5和50 mg*kg-1, 分别给药3,6和12 d,对照组给等容量的溶媒。酶学测定肝微粒体细胞色素P450 (CYP),尿苷二磷酸葡萄糖醛酸转移酶(GT)和谷胱甘肽巯基转移酶(GST)活性。结果 18α-GL抑制苯胺羟化酶,乙氧异唑脱乙基酶和红霉素脱甲基酶活性,抑制率分别可达53.2%,47.3%和34.3%;增加GT1(底物为7-甲基-4-羟基-香豆素),GT2(底物为4-羟基联苯)和GST活性,分别可达29.9%,70.3%和48.3%。结论 18α-GL

  12. 不同库外保护时间和冷藏时间对滞育卵冷藏浸酸种孵化率的影响%Effect of protection and refrigeration time outside storeroom on hatching rate of acid-treated diapause silkworm(Bombyx mori)eggs

    Institute of Scientific and Technical Information of China (English)

    余武昌; 黎书明; 蒋满贵; 李国栋

    2012-01-01

    [Objective]The present experiment was carried out to investigate the effects of different protection and refrigeration time outside storeroom on hatching rate of acid-treated diapause silkworm eggs in order to provide references for better protecting and storing acid-treated silkworm eggs in future. [Method]The hatching rate and uniformity of acid-treated diapause eggs, obtained from the cross and reciprocal cross Fr hybrids of silkworm variety Liangguang 2,were investigated after protecting them outside the storeroom at 25℃ for 5-60 days and refrigerating at 3-5℃ for 100-175 days. [Result] After protected for 10-60 days and refrigerated for 100-175 days, the practical hatching rate of silkworm eggs was 90.33-97.33%, which met the demand of silkworm eggs quality standard (above 90.00%). Hatching of silkworm eggs was not finished on the same day after refrigerated far 100-175 days and protected for 5-60 days. Silkworm eggs protected for 5-10 d hatched earlier and more uniform than that protected for longer time (15-60 days), that is, the longer the eggs protected, the more difference in their hatching time. [Conclusion]Therefore, protection lime outside storeroom did not affect practical batching rate but affected the uniformity of hatching rate, which was more obvious for the eggs protected within10 days.%[目的]验证库外保护时间和冷藏时间对滞育卵冷藏浸酸种孵化率的影响程度,为今后做好蚕种保护冷藏浸酸工作提供理论依据.[方法]以“两广二号”正、反交一代杂交种为研究对象,将不同库外保护时间(5~60d,25℃)和不同内库冷藏时间(100~175 d,3~5℃)的滞育卵,在同一时间以标准浸酸处理后统计其实用孵化率和孵化整齐度.[结果]蚕种冷藏时间100~175 d、库外保护时间10~60 d时,蚕种实用孵化率为90 33%~97.33%,符合蚕种质量标准规定的实用孵化率在90.00%以上的要求.冷藏时间100~175 d、库外保护时间5~60d的

  13. Quality Improvement of an Acid Treated Fuel Oil

    Directory of Open Access Journals (Sweden)

    Elizabeth Jumoke ETERIGHO

    2008-06-01

    Full Text Available The work on the quality improvement of fuel oil using acid treatment was carried out. The improvement of the fuel oil was done using sulphuric acid to remove contaminants. Sulphuric acid at different concentrations were mixed with the oil and kept at 45°C for four hours in the agitator vessel to allow reaction to take place. Acidic sludge was then drained off from the agitator and the oil was neutralized with sodium hydroxide. Centrifugation operation was used to extract the sulphonate dispersed in the oil. The treated and untreated oils were characterized for various properties and the results showed that the viscosity, total sulphur of fuel oil decreased from 6.0 to before 5.0 cst after acid treatment and 2.57 to 1.2225% w/w respectively while the flash point increased from 248 to 264°F. The water and sediment content increased from trace before to 0.6 after treatment. In addition, the calorific value increased from initial value of 44,368 to 44,805 and 44,715 kJ/kg at 50% and 75% conc. H2SO4 while decreasing with 85% and 90% conc. H2SO4. However, both carbon residue and ash content decreases with an increase in acid concentration.

  14. Fluoride removal performance of phosphoric acid treated lime ...

    African Journals Online (AJOL)

    2010-11-25

    Nov 25, 2010 ... 3Durban University of Technology, Durban, South Africa. Abstract. Fluoride in ... This may endanger human health as concentrations of alumin- .... Diameter (cm) (top/bottom). 10/10. 25/17.5. Maximum bed height. 30. 17.

  15. Denitrification in nitric-acid-treated cattle slurry during storage.

    NARCIS (Netherlands)

    Oenema, O.; Velthof, G.L.

    1993-01-01

    Lowering the pH of cattle slurry with HNO3 was used to reduce NH3 volatilization during storage and after application. Incubation studies were carried out to examine possible NO3 losses and N2O emission from HNO3 treated slurry during storage. Batches of cattle slurry were treated with various

  16. Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.

    Directory of Open Access Journals (Sweden)

    Priti Bahety

    Full Text Available BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA in Alzheimer's disease (AD, the mechanism by which DHA affects amyloid-β precursor protein (AβPP-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS. METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.

  17. Study to investigate the difference in reaction to intracutaneously and orally administered histamine between suspected histamine-intolerant patients and healthy volunteers

    NARCIS (Netherlands)

    den Broeder E; Kortboyer JM; Koers WJ; Bruijnzeel-Koomen CAFM; de Haan-Brand A; Wolthers BG; Breukelman H; Meulenbelt J; NVIC; ARO; afdeling Dermatologie en Allergologie (Academisch Ziekenhuis Utrecht); afdeling KCSB (Academisch Ziekenhuis Groningen)

    1996-01-01

    In een dubbelblinde placebo gecontroleerde, vergelijkende studie werd aan 16 histamine intolerante patienten en aan 16 gezonde proefpersonen histamine toegediend. Het doel van de studie was het ontwikkelen van een relatief simpele en betrouwbare test voor het stellen van de diagnose histamine-intol

  18. Orally Administered Salacia reticulata Extract Reduces H1N1 Influenza Clinical Symptoms in Murine Lung Tissues Putatively Due to Enhanced Natural Killer Cell Activity

    Science.gov (United States)

    Romero-Pérez, Gustavo A.; Egashira, Masayo; Harada, Yuri; Tsuruta, Takeshi; Oda, Yuriko; Ueda, Fumitaka; Tsukahara, Takamitsu; Tsukamoto, Yasuhiro; Inoue, Ryo

    2016-01-01

    Influenza is a major cause of respiratory tract infection. Although most cases do not require further hospitalization, influenza periodically causes epidemics in humans that can potentially infect and kill millions of people. To countermeasure this threat, new vaccines need to be developed annually to match emerging influenza viral strains with increased resistance to existing vaccines. Thus, there is a need for finding and developing new anti-influenza viral agents as alternatives to current treatments. Here, we tested the antiviral effects of an extract from the stems and roots of Salacia reticulata (SSRE), a plant rich in phytochemicals, such as salacinol, kotalanol, and catechins, on H1N1 influenza virus-infected mice. Following oral administration of 0.6 mg/day of SSRE, the incidence of coughing decreased in 80% of mice, and only one case of severe pulmonary inflammation was detected. Moreover, when compared with mice given Lactobacillus casei JCM1134, a strain previously shown to help increase in vitro natural killer (NK) cell activity, SSRE-administered mice showed greater and equal NK cell activity in splenocytes and pulmonary cells, respectively, at high effector cell:target cell ratios. Next, to test whether or not SSRE would exert protective effects against influenza in the absence of gut microbiota, mice were given antibiotics before being inoculated influenza virus and subsequently administered SSRE. SSRE administration induced an increase in NK cell activity in splenocytes and pulmonary cells at levels similar to those detected in mice not treated with antibiotics. Based on our results, it can be concluded that phytochemicals in the SSRE exerted protective effects against influenza infection putatively via modulation of the immune response, including enhancement of NK cell activity, although some protective effects were not necessarily through modulation of gut microbiota. Further investigation is necessary to elucidate the molecular mechanisms underlying the protective effects of SSRE against influenza infection. PMID:27066007

  19. Efficacy of bath and orally administered praziquantel and fenbendazole against Lepidotrema bidyana Murray, a monogenean parasite of silver perch, Bidyanus bidyanus (Mitchell).

    Science.gov (United States)

    Forwood, J M; Harris, J O; Deveney, M R

    2013-11-01

    We investigated the efficacy of praziquantel (PZQ) and fenbendazole (FBZ), each administered by bath and orally, against the monogenean Lepidotrema bidyana Murray, a gill parasite of the freshwater fish silver perch, Bidyanus bidyanus (Mitchell). PZQ and FBZ were each administered by bath at 10 mg L⁻¹ for 48 h and on surface-coated feed pellets at 75 mg kg⁻¹ per body weight (BW) per day for 6 days. Bath treatments of PZQ and FBZ had an efficacy of 99% and 91%, respectively, against adult L. bidyana. Oral treatments of PZQ and FBZ had an efficacy of 79% and 95%, respectively, against adult L. bidyana. Fish rejected feed pellets surface-coated with PZQ, suggesting that palatability of surface-coated PZQ-medicated feed is poor, which undermined efficacy. In all trials, some juvenile parasites were present on fish after treatment during efficacy assessment, indicating that efficacy may be lower against juvenile parasites or that recruitment occurred post-treatment, demonstrating that repeat treatments are necessary to effectively control L. bidyana in aquaculture.

  20. Orally administered glycidol and its fatty acid esters as well as 3-MCPD fatty acid esters are metabolized to 3-MCPD in the F344 rat.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Akagi, Jun-ichi; Fujiwara, Satoshi; Ochiai, Ryosuke; Tsujino, Kazushige; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-12-01

    IARC has classified glycidol and 3-monochloropropane-1,2-diol (3-MCPD) as group 2A and 2B, respectively. Their esters are generated in foodstuffs during processing and there are concerns that they may be hydrolyzed to the carcinogenic forms in vivo. Thus, we conducted two studies. In the first, we administered glycidol and 3-MCPD and associated esters (glycidol oleate: GO, glycidol linoleate: GL, 3-MCPD dipalmitate: CDP, 3-MCPD monopalmitate: CMP, 3-MCPD dioleate: CDO) to male F344 rats by single oral gavage. After 30 min, 3-MCPD was detected in serum from all groups. Glycidol was detected in serum from the rats given glycidol or GL and CDP and CDO in serum from rats given these compounds. In the second, we examined if metabolism occurs on simple reaction with rat intestinal contents (gastric, duodenal and cecal contents) from male F344 gpt delta rats. Newly produced 3-MCPD was detected in all gut contents incubated with the three 3-MCPD fatty acid esters and in gastric and duodenal contents incubated with glycidol and in duodenal and cecal contents incubated with GO. Although our observation was performed at 1 time point, the results showed that not only 3-MCPD esters but also glycidol and glycidol esters are metabolized into 3-MCPD in the rat.

  1. Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma.

    Science.gov (United States)

    Vail, D M; Husbands, B D; Kamerling, S G; Simpson, H; Kurzman, I D; McDonnell, A

    2012-01-01

    Idarubicin, a PO bioavailable anthracycline antibiotic-class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery. The primary objective of this study was to determine the maximally tolerated dose (MTD), dose-limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD. Client-owned dogs with measurable lymphoma. Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines. The MTD in dogs > 15 kg body weight was 22 mg/m(2) . Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol. PO administered idarubicin was generally well-tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated-dose, randomized clinical trials. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  2. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Zheng, Suqing [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Huang, Jeffrey T.-J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Honda, Tadashi [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Dinkova-Kostova, Albena T., E-mail: a.dinkovakostova@dundee.ac.uk [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States)

    2015-09-25

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in multiple organs. • Chronic dietary administration of TBE-31 at doses that show efficacy is not toxic.

  3. Urinary recovery of orally administered chromium 51-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in healthy adult male Beagles.

    Science.gov (United States)

    Frias, Rafael; Steiner, Jörg M; Williams, David A; Sankari, Satu; Westermarck, Elias

    2012-05-01

    Objective-To provide values for gastrointestinal permeability and absorptive function tests (GIPFTs) with chromium 51 ((51)Cr)-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in Beagles and to evaluate potential correlations between markers. Animals-19 healthy adult male Beagles. Procedures-A test solution containing 3.7 MBq of (51)Cr-labeled EDTA, 2 g of lactulose, 2 g of rhamnose, 2 g of d-xylose, 1 g of 3-O-methyl-d-glucose, and 8 g of sucrose was administered intragastrically to each dog. Urinary recovery of each probe was determined 6 hours after administration. Results-Mean ± SD (range) percentage urinary recovery was 6.3 ± 1.6% (4.3% to 9.7%) for (51)Cr-labeled EDTA, 3.3 ± 1.1% (1.7% to 5.3%) for lactulose, 25.5 ± 5.0% (16.7% to 36.9%) for rhamnose, and 58.8% ± 11.0% (40.1% to 87.8%) for 3-O-methyl-d-glucose. Mean (range) recovery ratio was 0.25 ± 0.06 (0.17 to 0.37) for (51)Cr-labeled EDTA to rhamnose, 0.13 ± 0.04 (0.08 to 0.23) for lactulose to rhamnose, and 0.73 ± 0.09 (0.60 to 0.90) for d-xylose to 3-O-methyl-d-glucose. Median (range) percentage urinary recovery was 40.3% (31.6% to 62.7%) for d-xylose and 0% (0% to 0.8%) for sucrose. Conclusions and Clinical Relevance-Reference values in healthy adult male Beagles for 6 of the most commonly used GIPFT markers were determined. The correlation between results for (51)Cr-labeled EDTA and lactulose was not as prominent as that reported for humans and cats; thus, investigators should be cautious in the use and interpretation of GIPFTs performed with sugar probes in dogs with suspected intestinal dysbiosis.

  4. Factors that Influence the Immunological Adjuvant Effect of Lactobacillus fermentum PC1 on Specific Immune Responses in Mice to Orally Administered Antigens

    Directory of Open Access Journals (Sweden)

    Meera Esvaran

    2016-07-01

    Full Text Available This study examined the influences of the dosage of the adjuvant, the nature of the antigen and the host genetics on the capacity of L. fermentum PC1 (PC1 to function as an oral adjuvant. BALB/c and DBA/1 mice were vaccinated with either ovalbumin (OVA or Salmonella Typhimurium on days 0 and 14, Mice were also dosed with the PC1 (108 CFU or 1011 CFU per dose per mouse with the antigens (days 0 and 14 and alone (days −1 and 13. The higher PC1 dose elicited a greater specific serum IgG2a response than IgG1 for both antigens and mice strains, indicating a Th1-biased humoral immune response. The Th1 bias was also observed at the cellular level with greater specific IFN-γ levels than IL-4 and IL-10 with both antigen types and mouse strains. With the particulate antigen, the lower dose of PC1 elicited a Th1 bias at the cellular level, but a balanced Th1/Th2 response at the systemic humoral level. With the soluble antigen, a strong Th1-biased response occurred at the cellular level while the systemic humoral response was Th2-biased. In conclusion, PC1 at the higher dose was an excellent Th1 adjuvant, which was unaffected by the nature of the antigen or the host’s genetic background.

  5. Effect of orally administered betel leaf (Piper betle Linn.) on digestive enzymes of pancreas and intestinal mucosa and on bile production in rats.

    Science.gov (United States)

    Prabhu, M S; Platel, K; Saraswathi, G; Srinivasan, K

    1995-10-01

    The influence of two varieties of betel leaf (Piper betle Linn.) namely, the pungent Mysore and non-pungent Ambadi, was examined on digestive enzymes of pancreas and intestinal mucosa and on bile secretion in experimental rats. The betel leaves were administered orally at two doses which were either comparable to human consumption level or 5 times this. The results indicated that while these betel leaves do not influence bile secretion and composition, they have a significant stimulatory influence on pancreatic lipase activity. Besides, the Ambadi variety of betel leaf has a positive stimulatory influence on intestinal digestive enzymes, especially lipase, amylase and disaccharidases. A slight lowering in the activity of these intestinal enzymes was seen when Mysore variety of betel leaf was administered, and this variety also had a negative effect on pancreatic amylase. Further, both the betel leaf varieties have shown decreasing influence on pancreatic trypsin and chymotrypsin activities.

  6. Study to investigate the difference in reaction to intracutaneously and orally administered histamine between suspected histamine-intolerant patients and healthy volunteers

    NARCIS (Netherlands)

    den Broeder E; Kortboyer JM; Koers WJ; Bruijnzeel-Koomen CAFM; de Haan-Brand A; Wolthers BG; Breukelman H; Meulenbelt J; NVIC; ARO; afdeling Dermatologie en Allergologie (Academisch Ziekenhuis Utrecht); afdeling KCSB (Academisch Ziekenhuis Groningen)

    1996-01-01

    In een dubbelblinde placebo gecontroleerde, vergelijkende studie werd aan 16 histamine intolerante patienten en aan 16 gezonde proefpersonen histamine toegediend. Het doel van de studie was het ontwikkelen van een relatief simpele en betrouwbare test voor het stellen van de diagnose

  7. PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Boonstra, Jennifer L; Barbosa, Lorraine; Van Bonn, William G; Johnson, Shawn P; Gulland, Frances M D; Cox, Sherry K; Martin-Jimenez, Tomas

    2015-09-01

    Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

  8. In vitro antimicrobial activity and MIC quality control guidelines of RPR 106972 (RPR 112808/RPR106950): a novel orally administered streptogramin combination. The Quality Control Study Group.

    Science.gov (United States)

    Putnam, S D; Jones, R N; Johnson, D M

    1997-07-01

    RPR 106972 is a novel oral streptogramin combination with reported therapeutic potency against Gram-positive and certain respiratory tract pathogens. MICs for RPR 106972, quinupristin/dalfopristin, and seven comparison drugs were determined by the reference methods against 337 strains selected to define spectrum and potency. RPR 106972 demonstrated antimicrobial activity against oxacillin-susceptible and -resistant Staphylococcus aureus (MIC ranges of 0.12 to 2 micrograms/ml and 0.5 to 2 micrograms/ml, respectively), and coagulase-negative staphylococci were also inhibited by RPR 106972 (MIC90, RPR 106972 was highly active with MIC results at RPR 106972 inhibited Corynebacterium jeikeium (MIC90, 0.5 microgram/ml). Moraxella catarrhalis (MIC90, 0.25 microgram/ml), and some Haemophilus influenzae (MIC50, 2 micrograms/ml). RPR 106972 and quinupristin/dalfopristin demonstrated little activity against Enterococcus faecalis (MIC90s, 4 to 32 micrograms/ml) as compared to Enterococcus faecium (MIC90s, 0.5 to 1 microgram/ml) and other Enterococcus ssp. (MIC90s, 1 microgram/ml). Studies to establish MIC quality-control guidelines indicated the following ranges: for E. faecalis ATCC 29212, 0.5 to 4 micrograms/ml; for S. aureus ATCC 29213, 0.25 to 1 microgram/ml; and for Streptococcus pneumoniae ATCC 49619, 0.06 to 0.5 microgram/ml. The results of this study indicate that the in vitro activity of RPR 106972 against Gram-positive bacteria and selected Gram-negative respiratory organisms is promising and warrants additional studies of pharmacokinetics, and in vivo infection model dynamics.

  9. Effects of orally administered fumonisin B₁ (FB₁), partially hydrolysed FB₁, hydrolysed FB₁ and N-(1-deoxy-D-fructos-1-yl) FB₁ on the sphingolipid metabolism in rats.

    Science.gov (United States)

    Hahn, Irene; Nagl, Veronika; Schwartz-Zimmermann, Heidi Elisabeth; Varga, Elisabeth; Schwarz, Christiane; Slavik, Veronika; Reisinger, Nicole; Malachová, Alexandra; Cirlini, Martina; Generotti, Silvia; Dall'Asta, Chiara; Krska, Rudolf; Moll, Wulf-Dieter; Berthiller, Franz

    2015-02-01

    Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos-1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially. We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC-MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans.

  10. The CD28/CTLA-4-B7 signaling pathway is involved in both allergic sensitization and tolerance induction to orally administered peanut proteins.

    NARCIS (Netherlands)

    Wijk, F. van; Nierkens, S.; Jong, W. de; Wehrens, E.J.; Boon, L.; Kooten, P. van; Knippels, L.M.; Pieters, R.

    2007-01-01

    Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one

  11. A multiple-dose, double-blind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan in patients with pain following orthopaedic surgery

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Strauss, W

    1994-01-01

    In this multiple-dose, double-blind study 100 patients with moderate, severe or very severe pain following orthopaedic surgery were randomly assigned to receive ketorolac, a non-steroidal anti-inflammatory drug with potent analgesic properties (10 mg), or the standard regimen of Ketogan (a......-mg doses of oral ketorolac are as effective as Ketogan for the treatment of pain following orthopaedic surgery. Ketorolac appears to be better tolerated than Ketogan since significantly fewer patients reported adverse events (P = 0.004) when taking ketorolac....

  12. Orally administered DTPA di-ethyl ester for decorporation of (241)Am in dogs: Assessment of safety and efficacy in an inhalation-contamination model.

    Science.gov (United States)

    Huckle, James E; Sadgrove, Matthew P; Pacyniak, Erik; Leed, Marina G D; Weber, Waylon M; Doyle-Eisele, Melanie; Guilmette, Raymond A; Agha, Bushra J; Susick, Robert L; Mumper, Russell J; Jay, Michael

    2015-07-01

    Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA)-approved for decorporation of (241)Am; however, an oral product is considered more amenable in a mass casualty situation. The di-ethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination. Single-dose decorporation efficacy of C2E2 administered 24-h post contamination was determined in beagle dogs using a (241)Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test. Oral administration of C2E2 significantly increased (241)Am elimination over untreated controls and significantly reduced the retention of (241)Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic. The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of (241)Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies.

  13. Orally Administered DTPA Di-ethyl Ester for Decorporation of 241Am in dogs: Assessment of Safety and Efficacy in an Inhalation-Contamination Model

    Science.gov (United States)

    Huckle, James E.; Sadgrove, Matthew P.; Pacyniak, Erik; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Agha, Bushra J.; Susick, Robert L.; Mumper, Russell J.; Jay, Michael

    2016-01-01

    Purpose Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA) approved for decorporation of 241Am, however, an oral product is considered more amenable in a mass casualty situation. The diethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination. Materials and methods Single dose decorporation efficacy of C2E2 administered 24-hours post contamination was determined in beagle dogs using a 241Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test. Results Oral administration of C2E2 significantly increased 241Am elimination over untreated controls and significantly reduced the retention of 241Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic. Conclusions The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of 241Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies. PMID:25912343

  14. The immuno-regulatory impact of orally-administered Hypericum perforatum extract on Balb/C mice inoculated with H1n1 influenza A virus.

    Directory of Open Access Journals (Sweden)

    Nan Huang

    Full Text Available Hypericumperforatum (H. perforatum ethanol extract has been found to inhibit lipopolysaccharide-induced production of inflammatory mediators and cytokines in cultured macrophages. Therefore, it may be able to protect the host from excessive inflammation during viral infection. In the current study, the immune-regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells, the extract (30 µg/mL significantly inhibited influenza virus induced monocyte chemotactic protein (MCP-1 and interferon-γ induced protein 10 kD (IP-10, but dramatically increased interleukin-6 (IL-6. In mice inoculated intranasally with 10(7.9 EID50 of Influenza A/PR/8/34 H1N1 (high dose, daily oral treatment of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung viral titer, bronchoalveolar lavage (BAL pro-inflammatory cytokine and chemokine levels, and the infiltration of pro-inflammatory cells in the lung 5 days post-inoculation, as compared to ethanol vehicle treated mice. Transcription of suppressor of cytokine signaling 3 (SOCS3 was increased by H. perforatum extract both in A549 cells and BALB/c mice, which could have interrupted anti-viral immune response and thus led to the inefficient viral clearance and increased lung inflammation. H. perforatum treatment resulted in minor reduction in viral titer without affecting body weight when mice were inoculated with a lower dose (~10(5.0 EID50 and H. perforatum was applied in the later phase of infection. Mice challenged intranasally with high dose of influenza virus (10(7.9 EID50 suffered from a higher mortality rate when dosed with H. perforatum extract. In conclusion, the current study showed that SOCS3 elevation by H. perforatum may cause impaired immune defense against influenza virus infection and lead to higher mortality.

  15. Response of intestinal cells and macrophages to an orally administered cellulose-PEG based polymer as a potential treatment for intractable edemas.

    Science.gov (United States)

    Esposito, Annaclaudia; Sannino, Alessandro; Cozzolino, Anna; Quintiliano, Sergio Nappo; Lamberti, Monica; Ambrosio, Luigi; Nicolais, Luigi

    2005-07-01

    The elimination of water from the body represents a fundamental therapeutic goal in those diseases in which oedemas occur. Aim of this work is the design of a material able to absorb large amount of water to be used, by oral administration, in those cases in which resistance to diuretics appears. Sorption and mechanical properties of the cellulose based superabsorbent hydrogel acting as a water elimination system have been modulated through the insertion of molecular spacers between the crosslinks. Starting polymers are the sodium salt of carboxymethylcellulose (CMCNa), a polyelectrolyte cellulose derivative, and the hydroxyethylcellulose (HEC), a non-polyelectrolyte derivative. Polyethyleneglycol (PEG) with various molecular weights, has been linked by its free ends at two divinylsulfone (DVS) crosslinker molecules, in order to increase the average distance between two crosslinking sites and thus acting as spacer. Both the effect of concentration and molecular weight of the spacer resulted to significantly affect the hydrogel final sorption properties and thus the efficiency of the body water elimination system. Biocompatibility studies have been performed to test the hydrogel compatibility with respect to intestinal and macrophages cell lines. To investigate the effects of intestinal cells conditioned media after the contact with the gel on macrophages nitric oxide release tests have been carried out.

  16. Orally administered Salacia reticulata extract reduces H1N1 influenza clinical symptoms in murine lung tissues putatively due to enhanced natural killer cell activity

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Romero-Pérez

    2016-03-01

    Full Text Available Influenza is a major cause of respiratory tract infection. Although most cases do not require further hospitalization, influenza periodically causes epidemics in humans that can potentially infect and kill millions of people. To countermeasure this threat, new vaccines need to be developed annually to match emerging influenza viral strains with increased resistance to existing vaccines. Thus, there is a need for finding and developing new anti-influenza viral agents as alternatives to current treatments. Here, we tested the antiviral effects of an extract from the stems and roots of Salacia reticulata (SSRE, a plant rich in phytochemicals such as salacinol, kotalanol and catechins, on H1N1 influenza virus-infected mice. Following oral administration of 0.6 mg/day of SSRE, the incidence of coughing decreased in 80% of mice, and only one case of severe pulmonary inflammation was detected. Moreover, when compared with mice given Lactobacillus casei JCM1134, a strain previously shown to help increase in vitro NK cell activity, SSRE-administered mice showed greater and equal NK cell activity in splenocytes and pulmonary cells, respectively, at high effector cell:target cell ratios. Next, to test whether or not SSRE would exert protective effects against influenza in the absence of gut microbiota, mice were given antibiotics before being inoculated influenza virus and subsequently administered SSRE. SSRE administration induced an increase in NK cell activity in splenocytes and pulmonary cells at levels similar to those detected in mice not treated with antibiotics. Based on our results, it can be concluded that phytochemicals in the SSRE exerted protective effects against influenza infection putatively via modulation of the immune response including enhancement of NK cell activity, although some protective effects were not necessarily through modulation of gut microbiota. Further investigation is necessary to elucidate the molecular mechanisms underlying the protective effects of SSRE against influenza infection.

  17. An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

    Science.gov (United States)

    Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

    2015-01-01

    Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid receptor antagonist, regulates obese-related factors in mice.

    Science.gov (United States)

    Marczak, Ewa D; Jinsmaa, Yunden; Myers, Page H; Blankenship, Terry; Wilson, Ralph; Balboni, Gianfranco; Salvadori, Severo; Lazarus, Lawrence H

    2009-08-15

    Orally active dual mu-/delta-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH(2)-Ph (MZ-2) was applied to study body weight gain, fat content, bone mineral density, serum insulin, cholesterol and glucose levels in female ob/ob (B6.V-Lep/J homozygous) and lean wild mice with or without voluntary exercise on wheels for three weeks, and during a two week post-treatment period under the same conditions. MZ-2 (10mg/kg/day, p.o.) exhibited the following actions: (1) reduced body weight gain in sedentary obese mice that persisted beyond the treatment period without effect on lean mice; (2) stimulated voluntary running on exercise wheels of both groups of mice; (3) decreased fat content, enhanced bone mineral density (BMD), and decreased serum insulin and glucose levels in obese mice; and (4) MZ-2 (30 microM) increased BMD in human osteoblast cells (MG-63) comparable to naltrexone, while morphine inhibited mineral nodule formation. Thus, MZ-2 has potential application in the clinical management of obesity, insulin and glucose levels, and the amelioration of osteoporosis.

  19. Effects of Long-term Use of Polyphenols on the Absorption and Tissue Distribution of Orally Administered Metformin and Atenolol in Rats

    Directory of Open Access Journals (Sweden)

    Saad Abdulrahman Hussain

    2013-06-01

    Full Text Available Aim: To evaluate the effect of long-term use of silibinin, epigallocatechin (ECGC, quercetin and rutin on the absorption and tissue distribution of metformin and atenolol. Materials and Methods: Thirty male rats were used, allocated into 5 groups and treated as follow: 1st group treated with olive oil and served as control; the other 4 groups were treated with either silibinin, EPGC, quercetin or rutin, administered orally as oily solutions for 30 days. At day 30, a 300mg/kg metformin and 50mg/kg atenolol were administered orally; 3.0 hrs later, the animals were sacrificed and blood samples, tissues of brain, kidney and liver were obtained for evaluation of the drugs level. Results: The polyphenols increased both serum and tissue levels of metformin compared with controls. This effect was relatively varied according to the structural differences among flavonoids. Conclusion: Long-term use of supraphysiological doses of flavonoids increase absorption of Zn, Cu and Fe and their tissue availability in brain, kidney and liver; this effect seems to be different with variations in structural features. [J Intercult Ethnopharmacol 2013; 2(3.000: 147-154

  20. Comparative effect of orally administered sodium butyrate before or after weaning on growth and several indices of gastrointestinal biology of piglets

    DEFF Research Database (Denmark)

    Le Gall, Maud; Gallois, Mélanie; Sève, Bernard;

    2009-01-01

    Sodium butyrate (SB) provided orally favours body growth and maturation of the gastrointestinal tract (GIT) in milk-fed pigs. In weaned pigs, conflicting results have been obtained. Therefore, we hypothesised that the effects of SB (3 g/kg DM intake) depend on the period (before v. after weaning......) of its oral administration. From the age of 5 d, thirty-two pigs, blocked in quadruplicates within litters, were assigned to one of four treatments: no SB (control), SB before (for 24 d), or after (for 11-12 d) weaning and SB before and after weaning (for 35-36 d). Growth performance, feed intake...... and various end-point indices of GIT anatomy and physiology were investigated at slaughter. The pigs supplemented with SB before weaning grew faster after weaning than the controls (P intake was higher in pigs supplemented with SB before or after weaning (P

  1. Methylglyoxal (MG) and cerebro-renal interaction: does long-term orally administered MG cause cognitive impairment in normal Sprague-Dawley rats?

    Science.gov (United States)

    Watanabe, Kimio; Okada, Kana; Fukabori, Ryoji; Hayashi, Yoshimitsu; Asahi, Koichi; Terawaki, Hiroyuki; Kobayashi, Kazuto; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-01-07

    Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4-6 months of age) and late phase (7-12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

  2. Orally administered lactoperoxidase increases expression of the FK506 binding protein 5 gene in epithelial cells of the small intestine of mice: a DNA microarray study.

    Science.gov (United States)

    Wakabayashi, Hiroyuki; Miyauchi, Hirofumi; Shin, Kouichirou; Yamauchi, Koji; Matsumoto, Ichiro; Abe, Keiko; Takase, Mitsunori

    2007-09-01

    Lactoperoxidase (LPO) is a component of milk and other external secretions. To study the influence of ingested LPO on the digestive tract, we performed DNA microarray analysis of the small intestine of mice administered LPO. LPO administration upregulated 78 genes, including genes involved in metabolism, immunity, apoptosis, and the cell cycle, and downregulated nine genes, including immunity-related genes. The most upregulated gene was FK506 binding protein 5 (FKBP5), a glucocorticoid regulating immunophilin. The upregulation of this gene was confirmed by quantitative RT-PCR in other samples. In situ hybridization revealed that expression of the FKBP5 gene in the crypt epithelial cells of the small intestine was enhanced by LPO. These results suggest that ingested LPO modulates gene expression in the small intestine and especially increases FKBP5 gene expression in the epithelial cells of the intestine.

  3. Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways.

    Science.gov (United States)

    Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Ali, Shakir; Bahcecioglu, Ibrahim H; Guler, Osman; Ozercan, Ibrahim; Ilhan, Necip; Kucuk, Omer

    2014-01-01

    Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.

  4. Effect of protection and refrigeration time alteration on hatching rate of acid-treated silkworm (Bombyx mori) eggs%不同库外保护时间和冷藏时间对冷藏浸酸种孵化率的影响

    Institute of Scientific and Technical Information of China (English)

    余武昌; 蒋满贵; 李国栋; 阳诚; 何珊珊; 莫云霞; 李燕飞

    2011-01-01

    [目的]进一步验证库外保护时间和冷藏时间对冷藏浸酸种孵化率的影响程度.[方法]以"两广二号"正、反交一代杂交种为研究对象,将不同库外保护时间(2~7 d,25℃)和不同内库冷藏时间(30~110 d,3~5℃)的蚕卵,经同一标准浸酸处理后统计其冷藏浸酸种孵化率.[结果]冷藏时间相同,库外保护时间短的冷藏浸酸种比库外保护时间长的发育快,而库外保护时间间隔越长,蚕种孵化整齐度越差.随着冷藏时间的延长,不同库外保护时间的冷藏浸酸种实用孵化率提高明显,冷藏时间达到70 d以上,其实用孵化率全部达到生产要求(90.0%以上);而且不同库外保护时间的冷藏浸酸种孵化整齐度也明显提高.[结论]冷藏浸酸种的卵龄差过大、内库冷藏时间不足等容易出现孵化不整齐.因此,在生产上应尽量减少冷藏浸酸种补种,防止蚕种孵化不整齐.%[Objective]The present experiment was aimed to investigate the effect of altering protection and refrigeration times outside storeroom on hatching rate of acid-treated silkworm (Bombyx mori) eggs. [Method]The hatching rate of acid-treated eggs (in HCl solution, 48℃), obtained from the cross and reciprocal cross species of silkworm variety Liangguang 2, was investigated after protecting them outside storeroom at 25℃ for 2-7 days and refrigerating at 3-5℃ for 30-110 days. [Result]The growth in the eggs kept for same refrigeration time was found faster in shorter protection time treated eggs compared to those kept for longer protection time. Further, the uniformity of hatching was lesser in those eggs which have been kept for longer protection time. While the practical hatching rate increased significantly in silkworm eggs kept for different protection time and the longer refrigeration duration. The hatching rate increased to more than 90% after refrigerating the eggs for 70 days, which was equal to the production demand, also the

  5. Clinical Observation on Glycyrrhizic Acid Compound Combined with Paeonol on Allergic Contact Dermatitis%复方甘草酸苷联合丹皮酚软膏治疗48例变应性接触性皮炎临床观察

    Institute of Scientific and Technical Information of China (English)

    位争伟; 杜朝阳; 姜恩林

    2014-01-01

    目的:探讨复方甘草酸苷联合丹皮酚软膏治疗变应性接触性皮炎( ACD)的临床。方法:96例ACD患者被随机分为对照组和治疗组,每组各为48例。对照组口服复方甘草酸苷片3次/d,2片/次。治疗组在对照组基础上外用丹皮酚软膏,2次/d。治疗后观察和比较两组临床疗效、症状积分和免疫因子水平变化及不良反应情况。结果:治疗组治疗后痊愈率和总有效率分别达到66.67%和85.42%,显著高于对照组痊愈率和总有效率( P<0.05);治疗组治疗1、2和3周后症状积分分别为(5.23±1.1)分、(3.07±1.08)分和(1.32±0.82)分,均显著低于治疗前和对照组治疗后水平(P<0.05);治疗后sIL-2R为(2.11±0.76)ng/mL,显著低于对照组(P<0.05),而IL-2和IFN-γ水平为(28.14±2.37)pg/mL和(28.04±11.06)pg/mL,显著高于对照组(P<0.05);两组不良反应率无统计学意义(P<0.05)。结论:口服复方甘草酸苷联合外用丹皮酚软膏,能显著改善ACD患者症状评分,降低炎性因子水平,不良反应少,疗效显著优于单用复方甘草酸苷。%Objective: To investigate the clinical observation of glycyrrhizic acid compound combined with Paeonol on allergic contact dermatitis (ACD).Methods:Ninety six patients with ACD were randomly divided into the control group (n=48) and the observation group (n=48).The control group applied oral compound glycyrrhizin glucoside tablets three times a day , two tablets each time.The observation group applied Paeonol ointment topically two times a day except form the treatment of the control group .The clinical curative effect, symptom integral and immune factor level change as well as the adverse reactions between two groups after treatment were ob -served and compared .Results:The curative rate and total effective rate after treatment in the observation groups were 66.67%and 85. 42% respectively, which

  6. Effects of hydrofluoric acid-treated titanium micro/nano surface on the biological activity of bone marrow mesenchymal stem cells%氢氟酸酸蚀形成的两种不同微/纳米表面对骨髓间充质干细胞生物活性的影响

    Institute of Scientific and Technical Information of China (English)

    申明明; 李艳荣; 齐亚平; 付亁; 秦东泽; 梁建飞; 赵云转

    2015-01-01

    AIM:To evaluate the effects of hydrofluoric ( HF) acid-treated titanium surfaces on the biologi-cal activity of bone marrow mesenchymal stem cells ( BMMSCs ) . METHODS: Titanium plates were divided into 3 groups, the suface of the samples was polished in group A, etched by 12. 5 g/L HF acid for 1 min group B and etched by 12. 5 g/L HF acid for 15 min Group C. The surface of the sample was observed by scanning electron micros-copy ( SEM ) . The suxface chemical composition was assessed by energy dispersive X-Ray spectroscopy detector ( EDS) . Contact angles were detected by drop method . BMMSCs adhesion and morphology were examined by confocal microscopy and SEM. Cell viability and ALP activity were assessed by MTT assay and ALP detection kit. RESULTS:Micro/nano-scale surface structures were formed after HF etching. The sample surfaces of group B and C were loaded with fluorine. Contact angle of etching groups was significantly smaller than that of polishing group. HF-treated titani-um surfaces significantly promoted adhesion, proliferation and ALP activity of BMMSCs. Furthermore, the effects of group C was greater than those of group B. CONCLUSION:HF acid-etch may forme different size of micro/nano-scale structures and load with fluorineon on titanium surface;can improve the biological activity of BMMSCs.%目的:评价纯钛样品经12. 5 g/L氢氟酸(HF)酸蚀处理不同时间后形成的两种不同表面对骨髓间充质干细胞(BMMSCs)生物活性的影响. 方法:将纯钛钛片平均分为3组:A组抛光处理;B组12. 5 g/L HF酸蚀1 min;C组12. 5 g/L HF酸蚀15 min. X射线能谱仪分析( EDS)其表面化学成分;亲水性试验测量样品表面的接触角;激光共聚焦显微镜计数评价BMMSCs在样品表面的早期黏附;SEM观察观察样品表面形貌及黏附的细胞形态;MTT法检测细胞活性;碱性磷酸酶( ALP)试剂盒测定ALP活性. 结果:酸蚀后的两组样品都可形成微/纳米级表面形貌且载入氟元素;酸蚀后

  7. A dual-isotope-labeling method of studying the bioavailablity of hexaglutamyl folic acid relative to that of monoglutamyl folic acid in humans by using multiple orally administered low doses

    NARCIS (Netherlands)

    Boonstra, A.; Verhoef, P.; West, C.E.; Rhijn, van J.A.; Breemen, van R.B.; Lasaroms, J.J.P.; Garbis, S.D.; Katan, M.B.; Kok, F.J.

    2006-01-01

    Background: The bioavailability of dietary folate may be hampered by the need of the glutamate moieties to be deconjugated before absorption. Previous studies comparing the bioavailabilities of polyglutamyl and monoglutamyl folic acid had inconsistent results. Objective: The objective was to estimat

  8. Tumorigenic effects in Wistar rats orally administered benzo[a] pyrene for two years (gavage studies). Implications for human cancer risks associated with oral exposure to polycyclic aromatic hydrocarbons

    NARCIS (Netherlands)

    Kroese ED; Muller JJA; Mohn GR; Dortant PM; Wester PW; LEO; LPI; CSR

    2002-01-01

    Humans are exposed via the environment and via food to Polycyclic Aromatic Hydrocarbons (PAH), mixtures considered carcinogenic by IARC. A quantitative cancer risk assessment for oral exposure is hampered by the absence of adequate data. The need for experimental data is substantiated by the fact th

  9. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    Science.gov (United States)

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  10. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

    Directory of Open Access Journals (Sweden)

    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  11. Transcriptomic analysis reveals the flooding tolerant mechanism in flooding tolerant line and abscisic acid treated soybean.

    Science.gov (United States)

    Yin, Xiaojian; Hiraga, Susumu; Hajika, Makita; Nishimura, Minoru; Komatsu, Setsuko

    2017-03-01

    Soybean is highly sensitive to flooding stress and exhibits markedly reduced plant growth and grain yield under flooding conditions. To explore the mechanisms underlying initial flooding tolerance in soybean, RNA sequencing-based transcriptomic analysis was performed using a flooding-tolerant line and ABA-treated soybean. A total of 31 genes included 12 genes that exhibited similar temporal patterns were commonly changed in these plant groups in response to flooding and they were mainly involved in RNA regulation and protein metabolism. The mRNA expression of matrix metalloproteinase, glucose-6-phosphate isomerase, ATPase family AAA domain-containing protein 1, and cytochrome P450 77A1 was up-regulated in wild-type soybean under flooding conditions; however, no changes were detected in the flooding-tolerant line or ABA-treated soybean. The mRNA expression of cytochrome P450 77A1 was specifically up-regulated in root tips by flooding stress, but returned to the level found in control plants following treatment with the P450 inhibitor uniconazole. The survival ratio and root fresh weight of plants were markedly improved by 3-h uniconazole treatment under flooding stress. Taken together, these results suggest that cytochrome P450 77A1 is suppressed by uniconazole treatment and that this inhibition may enhance soybean tolerance to flooding stress.

  12. Nitric acid treated multi-walled carbon nanotubes optimized by Taguchi method

    Science.gov (United States)

    Shamsuddin, Shahidah Arina; Derman, Mohd Nazree; Hashim, Uda; Kashif, Muhammad; Adam, Tijjani; Halim, Nur Hamidah Abdul; Tahir, Muhammad Faheem Mohd

    2016-07-01

    Electron transfer rate (ETR) of CNTs can be enhanced by increasing the amounts of COOH groups to their wall and opened tips. With the aim to achieve the highest production amount of COOH, Taguchi robust design has been used for the first time to optimize the surface modification of MWCNTs by nitric acid oxidation. Three main oxidation parameters which are concentration of acid, treatment temperature and treatment time have been selected as the control factors that will be optimized. The amounts of COOH produced are measured by using FTIR spectroscopy through the absorbance intensity. From the analysis, we found that acid concentration and treatment time had the most important influence on the production of COOH. Meanwhile, the treatment temperature will only give intermediate effect. The optimum amount of COOH can be achieved with the treatment by 8.0 M concentration of nitric acid at 120 °C for 2 hour.

  13. Base catalyzed transesterification of acid treated vegetable oil blend for biodiesel production

    Energy Technology Data Exchange (ETDEWEB)

    Yusup, Suzana; Khan, Modhar Ali [Chemical Engineering Department, Universiti Teknologi PETRONAS, Seri Iskandar, Tronoh, Perak 31750 (Malaysia)

    2010-10-15

    Biodiesel can be produced from low cost non-edible oils and fats. However, most of these sources are of high free fatty acid content which requires two stage transesterification to reduce the acid value and produce biodiesel. The acid treatment step is usually followed by base transesterification since the latter can yield higher conversions of methyl esters at shorter reaction time when compared with acid catalyzed reaction. In the current study, base transesterification in the second stage of biodiesel synthesis is studied for a blend of crude palm/crude rubber seed oil that had been characterized and treated with acid esterification. Optimum conditions for the reaction were established and effect of each variable was investigated. The base catalyzed transesterification favored a temperature of 55 C with methanol/oil molar ratio of 8/1 and potassium hydroxide at 2% (ww{sup -1}) (oil basis). The conversion of methyl esters exceeded 98% after 5 h and the product quality was verified to match that for biodiesel with international standards. (author)

  14. [Characterization of the biological properties of acid-treated chrysotile-asbestos fibers].

    Science.gov (United States)

    Pylev, L N; Vasil'eva, L A; Stadnikova, N M; Smirnova, O V; Zubakova, L E; Vezentsev, A I; Gudkova, E A; Bakhtin, A I

    2006-01-01

    Boiling of chrysotile of the textile brand PRZh1-50 in concentrated hydrochloric acid for 10, 15, and 20 minutes gave rise to three chrysotile-asbestos samples. The content of MgO decreased from to 24, 19, and 9%, respectively. As compared with the baseline values, the number and force of positively charged electrical centers were less in the samples containing 24 and 19% MgO and more in the sample having 9% MgO; the negatively charged centers were present in the former two samples and absent in the third one. When the samples were intrapleurally administered to rats, their hemolytic activity, induction of active oxygen radicals, mutagenic activity (micronuclear test using murine bone marrow cells), and the frequency of mesotheliomas were less in the treated samples than in the baseline ones; but there were no differences between the treated samples. Thus, the altered physicochemical properties of the fibrillar surface of asbestos diminished its biological aggressiveness; however, increased treatment rates failed to lead to its further decrease. There was no relationship of the biological properties to the number and force of electric charges of the surface.

  15. Immunoreactivity of lactic acid-treated mare's milk after simulated digestion.

    Science.gov (United States)

    Fotschki, Joanna; Szyc, Anna; Wróblewska, Barbara

    2015-02-01

    The similarity of mare's milk to breast milk makes it an interesting substrate for the creation of dairy beverages. The aim of this study was to determine the immunoreactivity of the digested mare's milk products carried out by lactic acid fermentation with Lactobacillus casei LCY, Streptococcus thermophilus MK10 and Bifidobacterium animalis Bi30. Simulation of digestion with saliva, pepsin and pancreatin/bile salts was carried out. The immunoreactivity of the milk proteins was assessed by competitive ELISA. The separation of proteins was studied using a tricine SDS-PAGE method. It has been demonstrated that lactic acid fermentation significantly decreases the immunoreactivity of β-lactoglobulin, β-casein, κ-casein and bovine serum albumin. The level of reduction was connected to the type of bacterial strain. The simulated digestion processes caused the decline of immunoreactivity, and the decreases obtained in the experiment were as follows: lactoferrin: 95%, β-lactoglobulin: 94%, β-casein: 93%, α-lactalbumin: 82%, α-casein: 82%, bovine serum albumin: 76% and κ-casein: 37%. The results of the study indicated that microbial fermentation with tested strains is a valuable method for reducing the immunoreactivity of mare's milk proteins. However, further studies with other bacterial strains are needed to gain a higher level of elimination or total reduction of mare's milk immunoreactivity to possibly introduce fermented mare's milk into the diet of patients with immune-mediated digestive problems.

  16. Removal of chromium(VI) from wastewater using phosphoric acid treated activated carbon

    Science.gov (United States)

    Suganthi, N.

    2013-06-01

    Activated carbon prepared by phosphoric acid treatment of tamarind nuts (seeds) was investigated for the removal of Cr(VI) from aqueous solutions. The characteristics of phosphorylated tamarind nut carbon (PTNC) were evaluated for porosity and surface area. The effect of contact time, pH, adsorbent dose and particle size variation were studied to evaluate the potential applicability of carbon for treating Cr(VI) containing wastewater. The adsorbent data were modeled by Langmiur and Freundlich classical adsorption isotherms. The kinetic studies showed that Cr(VI) adsorption on PTNC was in compliance with the pseudo-second-order kinetic model. Desorption studies indicated that ion-exchange mechanism was operating. The continuous adsorption was studied in glass columns of 2.5 cm diameter using electroplating wastewater to ascertain the practical applicability of PTNC in large scale. The mechanism of adsorption was found to be ion-exchange process and was supported by FTIR spectroscopy. The surface modification after adsorption was confirmed by SEM studies.

  17. Investigation on surface structure of potassium permanganate/nitric acid treated poly(tetrafluoroethylene)

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Congli; Liu, Shuling; Gong, Tianlong; Gu, Aiqun; Yu, Zili, E-mail: ziliyu@scu.edu.cn

    2014-10-30

    Highlights: • A new transformation (conversion) mechanism of PTFE surface from a hydrophobicity to a hydrophilicity was proposed through the treatment of KMnO{sub 4}/HNO{sub 3}. • Chemical reactions or defluorination of PTFE described in the reported paper was testified to be a misconceived conclusion by the combination of several testing measurements (IR, XPS, XRD and so on) in our present work. • Deposition of manganese oxide and/or manganese hydroxide on PTFE surface contributed to the hydrophilic property of the modified PTFE with KMnO{sub 4}/HNO{sub 3} treated. • The deposition thickness on the modified PTFE surface was about 5 μm, which was significantly helpful in enhancing the adhesive strength of PTFE with other materials. - Abstract: In the previous articles concerning the treatment of poly(tetrafluoroethylene) (PTFE) with potassium permanganate/nitric acid mixture, the conversion of a hydrophobic to a hydrophilic surface was partially assigned to the defluorination of PTFE and then the introduction of carbonyl and hydroxyl groups into the defluorinated sites. In the present work, PTFE sheets were treated with potassium permanganate/nitric acid, and the surfaces before and after treatment were comparatively characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The surface sediments of the treated PTFE were also determined by atomic absorption spectroscopy (AAS). The results indicate that the conversion of the hydrophobicity to the hydrophilicity on the modified PTFE surface is mainly due to the deposition of hydrophilic manganese oxides which covered the fluorocarbon surface, and no detectable chemical reactions of PTFE occur in the treating process.

  18. Differences in oxygen reduction catalysis of platinised acid treated Showa Denko carbon nanofibres

    DEFF Research Database (Denmark)

    Veltzé, Sune; Yli-Rantala, Elina; Borghei, Maryam

    2011-01-01

    The use of carbon as support material for platinum nano-crystallites in polymer electrolyte fuel cells (PEFC) is a common method for increasing the electrochemical specific surface area (ECSA) of platinum. During fuel cell operation, the conditions that catalysts are subjected to lead to various ...

  19. Retinoic acid-treated pluripotent stem cells undergoing neurogenesis present increased aneuploidy and micronuclei formation.

    Directory of Open Access Journals (Sweden)

    Rafaela C Sartore

    Full Text Available The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC cells, embryonic stem (ES cells and induced pluripotent stem (iPS cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naïve cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal variation accompanies neurogenesis in vitro.

  20. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    Science.gov (United States)

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  1. Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism

    OpenAIRE

    Kailash Singh; Aung Moe Zaw; Revathi Sekar; Ahuja Palak; Allam, Ahmed A.; Jamaan Ajarem; Chow, Billy K. C.

    2016-01-01

    Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2 adrenergic receptor remains constant during the risk of heart failure. Beta blockers—the antagonistic molecules for beta-adrenergic receptors, function by slowing the heart rate, which there...

  2. Molecular Modeling of Acidic Treated PSTM-3T Polymer for Removal of Heavy Metal Ions by Experimental and Computational Studies

    Directory of Open Access Journals (Sweden)

    Natsagdorj Narantsogt

    2014-01-01

    Full Text Available The synthesized poly[N,N′-bis(3-silsesquioxanilpropyl-thiocarbamide] (PSTM-3T was used and the surface morphology and microstructure of it were analyzed by scanning electron microscopy with energy dispersive spectrometer (SEM/EDS. The molecular structure change of the PSTM-3T polymer of the PSTM-3T after treatment by acidic solution with different pHs was revealed using FT-IR experiments and ab initio calculations with density functional theory method. The sorption efficiency of the heavy metal ions depends on the molecular structure change of PSTM-3T after treatment of different pH aqueous solutions. After the treatment of acidic solution (pH = 2 of PSTM-3T, the polymer formed the tautomer state to increase the sorption efficiency for chromate ion. For the increment of pH value for acidic solution, the PSTM-3T polymer was dissociated to increase the sorption efficiency for copper ion.

  3. Structural and Biochemical Changes in Salicylic-Acid-Treated Date Palm Roots Challenged with Fusarium oxysporum f. sp. albedinis

    Directory of Open Access Journals (Sweden)

    Abdelhi Dihazi

    2011-01-01

    Full Text Available Histochemical and ultrastructural analyses were carried out to assess structural and biochemical changes in date palm roots pretreated with salicylic acid (SA then inoculated with Fusarium oxysporum f. sp. albedinis (Foa. Flavonoids, induced proteins, and peroxidase activity were revealed in root tissues of SA-treated plants after challenge by Foa. These reactions were closely associated with plant resistance to Foa. Host reactions induced after inoculation of SA-treated plants with Foa included the plugging of intercellular spaces, the deposition of electron-dense materials at the sites of pathogen penetration, and several damages to fungal cells. On the other hand, untreated inoculated plants showed marked cell wall degradation and total cytoplasm disorganization, indicating the protective effects provided by salicylic acid in treated plants.

  4. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Directory of Open Access Journals (Sweden)

    Ramazan Kurt

    Full Text Available Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α-based combination therapy in chronic hepatitis C virus (HCV infection. Previously, we reported that free fatty acid (FFA-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1, which is why the antiviral activity of IFN-α against HCV is impaired.To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α and Type III IFN (IFN-λ was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA in the FFA-treated HCV cell culture model was investigated.FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ, which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture. Pharmacological inhibitors of lysosomal degradation, such as ammonium chloride and bafilomycin, prevented IFNAR1 degradation in FFA-treated HCV cell culture. Activators of chaperone-mediated autophagy, including 6-aminonicotinamide and nutrient starvation, decreased IFNAR1 levels in Huh-7.5 cells. Co-immunoprecipitation, colocalization and siRNA knockdown experiments revealed that IFNAR1 but not IFNLR1 interacts with HSC70 and LAMP2A, which are core components of chaperone-mediated autophagy (CMA.Our study presents evidence indicating that chaperone-mediated autophagy targets IFNAR1 degradation in the lysosome in FFA-treated HCV cell culture. These results provide a mechanism for why HCV induced autophagy response selectively degrades type I but not the type III IFNAR1.

  5. Characterization of acid-treated carbon nanotube thin films by means of Raman spectroscopy and field-effect response

    Science.gov (United States)

    Zhang, Zhi-Bin; Li, Jiantong; Cabezas, Ana López; Zhang, Shi-Li

    2009-07-01

    By combining Raman spectroscopy with transistor transfer characteristics, acid treatment of single-walled carbon nanotubes (SWCNTs) in a mixture of concentrated HNO 3/H 2SO 4 has been characterized. The acid treatment results in a sharp decrease in the Raman resonant signals of the metallic SWCNTs but no observable change in those of the semiconducting SWCNTs. However, the acid treatment causes disappearing gate modulation of the thin-film transistors made of the SWCNTs, contrary to what would be expected referring to the Raman results. These experimental results suggest that the energy band of the semiconducting SWCNTs is significantly affected by absorbates induced by the acid treatment.

  6. Nitrous-Oxide Flux from Nitric-Acid-Treated Cattle Slurry Applied to Grassland under Semi-Controlled Conditions

    NARCIS (Netherlands)

    Velthof, G.L.; Oenema, O.

    1993-01-01

    Nitrous oxide (N2O) fluxes from cattle slurry after surface application to grassland were measured under semi-controlled environmental conditions during three periods in 1991. Three types of cattle slurry were examined; untreated slurry and slurries treated with nitric acid (HNO3) to pH 6.0 and 4.5.

  7. Ovine placental eluate immunoglobulins recognise isologous and third party acid-treated trophoblast microvesicle antigens in vitro

    Directory of Open Access Journals (Sweden)

    C.A. Omwandho

    2006-06-01

    Full Text Available Placental microvesicles were prepared from ovine placentae and immunoglobulins eluted with 0.5 M glycine buffer pH 2.5. The ability of eluate immunoglobulins to re-associate with isologous (self and third party acidified microvesicles was tested by ELISA. Ovine placental immunoglobulins re-associated with isologous and third party acidified microvesicles suggesting that at least 2 types of antigenic epitopes I and II may be expressed on the ovine placentae. Type I antigensmaybe present on placentae of all ovines while type II epitopes may be paternally derived, hence unique to each pregnancy. Analysis by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27 kDa, respectively, together giving a relative molecular weight of 158 kDa. Results suggest that immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the trophoblast, possibly defining a mechanism by which the foetus evades maternal immunological rejection.

  8. 口服益生菌Escherichia coli Nissle 1917调控断奶仔猪空肠黏膜屏障功能的机理研究%Study on the Mechanism of Orally Administered Probiotics Escherichia coli Nissle 1917 Regulating Intestine Barrier in Weaned Piglets

    Institute of Scientific and Technical Information of China (English)

    唐志如; 邓欢; 孙卫忠; 张小龙; 张翥

    2014-01-01

    旨在探讨口服益生菌Escherichia coli(E.coli) Nissle 1917调控病原菌E.coli Abbottstown攻毒或未攻毒21d断奶仔猪肠道屏障功能的机理.将20头21d断奶仔猪((6.35±0.38) kg)随机分为4组:(1)饲喂基础日粮的对照组(CON);(2)正试期口服E.coli Nissle 1917组(EcN);(3)预试期E.coli Abbottstown攻毒组(EcA);(4)预试期E.coli Abbottstown攻毒和正试期口服Ecoli Nissle 1917组(EcN+ EcA).每个处理5个重复,每个重复1头仔猪.试验分为3d预试期和21d正试期.预试期EcA和EcN+ EcA组的断奶仔猪接种5×109 E.coli Ab-bottstown.正试期EcN和EcN+EcA组仔猪每天每头口服1×1010E.coli Nissle 1917.试验结果表明,未攻毒的断奶仔猪中,与CON相比,口服1×1010E.coli Nissle 1917能显著改善生长性能(P<0.05),降低腹泻率,提高oc-cludin蛋白水平(P<0.05),显著降低空肠黏膜calprotectin蛋白水平(P<0.05),显著下调空肠黏膜蛋白激酶R(Protein kinase R,PKR)、toll样受体-2(Toll-like receptor-2,TLR-2)和真核起始因子-5A(eukaryotic initiation fac-tor-5A,eIF 5A)mRNA的相对表达丰度(P<0.05),上调空肠黏膜内皮生长因子(Endothelial growth factor,EGF)、肝细胞生长因子(Hepatocyte growth factor,HGF)、胰岛素样生长因子(Insulin-like growth factor,IGF-I)、三叶肽因子-3(trefoil peptide factor 3,TFF-3)mRNA的相对表达丰度(P<0.05);在E.coli Abbottstown攻毒的断奶仔猪中,与EcA组相比,口服1×1010E.coli Nissle 1917能显著改善生长性能(P<0.05),降低腹泻率,降低血清二胺氧化酶(DAO)活性(P<0.05)和一氧化氮(N())含量(P<0.05),下调空肠黏膜PKR、eIF-5A和TLR-2 mRNA相对表达丰度(P<0.05),显著降低空肠黏膜calprotectin蛋白水平和淋巴细胞数量(P<0.05),显著提高空肠黏膜oc-eludin蛋白水平(P<0.05),上调空肠黏膜IGF I、HGF、TFF-3和EGF mRNA相对表达丰度(P<0.05).本试验结果提示,口服1× 1010E.coli Nissle 1917能降低病原大肠杆菌攻毒或未攻毒21日龄断奶仔猪空肠黏膜屏障功能的损伤.

  9. Transcriptome analysis of acetic-acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance.

    Science.gov (United States)

    Lee, Yeji; Nasution, Olviyani; Choi, Eunyong; Choi, In-Geol; Kim, Wankee; Choi, Wonja

    2015-08-01

    Acetic acid inhibits the metabolic activities of Saccharomyces cerevisiae. Therefore, a better understanding of how S. cerevisiae cells acquire the tolerance to acetic acid is of importance to develop robust yeast strains to be used in industry. To do this, we examined the transcriptional changes that occur at 12 h post-exposure to acetic acid, revealing that 56 and 58 genes were upregulated and downregulated, respectively. Functional categorization of them revealed that 22 protein synthesis genes and 14 stress response genes constituted the largest portion of the upregulated and downregulated genes, respectively. To evaluate the association of the regulated genes with acetic acid tolerance, 3 upregulated genes (DBP2, ASC1, and GND1) were selected among 34 non-protein synthesis genes, and 54 viable mutants individually deleted for the downregulated genes were retrieved from the non-essential haploid deletion library. Strains overexpressing ASC1 and GND1 displayed enhanced tolerance to acetic acid, whereas a strain overexpressing DBP2 was sensitive. Fifty of 54 deletion mutants displayed enhanced acetic acid tolerance. Three chosen deletion mutants (hsps82Δ, ato2Δ, and ssa3Δ) were also tolerant to benzoic acid but not propionic and sorbic acids. Moreover, all those five (two overexpressing and three deleted) strains were more efficient in proton efflux and lower in membrane permeability and internal hydrogen peroxide content than controls. Individually or in combination, those physiological changes are likely to contribute at least in part to enhanced acetic acid tolerance. Overall, information of our transcriptional profile was very useful to identify molecular factors associated with acetic acid tolerance.

  10. Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

    Directory of Open Access Journals (Sweden)

    Ellouz Meriem

    2010-10-01

    Full Text Available Abstract Background Olive oil's beneficial effects are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. In this study, we assess the effects of virgin olive oil and its fractions on 2,4-D- induced oxidative damage in the liver of rats. Methods Male Wistar rats were randomly divided into eight groups of ten each: (C a control group, (D group that received 2,4-D (5 mg/kg b.w., (D/EVOO group treated with 2,4-D plus extra virgin olive oil, (D/OOHF group that received 2,4-D plus hydrophilic fraction, (D/OOLF group treated with 2,4-D plus lipophilic fraction, (EVOO group that received only extra virgin olive oil, (OOHF group given hydrophilic fraction and (OOLF group treated with lipophilic fraction. These components were daily administered by gavage for 4 weeks. Results A significant liver damage was observed in rats treated with 2,4-D via increased serum levels of transaminases and alkaline phosphatase, hepatic lipid peroxidation and decreased hepatic antioxidant enzyme activities, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The liver's fatty acid composition was also significantly modified with 2,4-D exposure. However, extra virgin olive oil and hydrophilic fraction intake during 2,4-D treatment induced a significant increase in the antioxidant enzyme activities and a decrease in the conjugated dienes (CD and thiobarbituric acid-reactive substances (TBARs levels in the liver. The lipophilic fraction supplemented to 2,4-D- treated rats did not show any improvement in the liver oxidative status while a marked improvement was detected in the hepatic fatty acid composition of rats supplemented with olive oil and the two fractions. Conclusion We concluded that the protective effect of olive oil against oxidative damage induced by 2,4-D is mainly related to the antioxidant potential of its hydrophilic fraction.

  11. DNA Methylation Changes in Valproic Acid-Treated HeLa Cells as Assessed by Image Analysis, Immunofluorescence and Vibrational Microspectroscopy

    Science.gov (United States)

    Veronezi, Giovana M. B.; Felisbino, Marina Barreto; Gatti, Maria Sílvia V.; Vidal, Benedicto de Campos

    2017-01-01

    Valproic acid (VPA), a well-known histone deacetylase inhibitor, has been reported to affect the DNA methylation status in addition to inducing histone hyperacetylation in several cell types. In HeLa cells, VPA promotes histone acetylation and chromatin remodeling. However, DNA demethylation was not checked in this cell model for standing effects longer than those provided by histone acetylation, which is a rapid and transient phenomenon. Demonstration of VPA-induced DNA demethylation in HeLa cells would contribute to understanding the effect of VPA on an aggressive tumor cell line. In the present work, DNA demethylation in VPA-treated HeLa cells was assessed by image analysis of chromatin texture, the abundance of 5-methylcytosine (5mC) immunofluorescence signals and Fourier transform-infrared (FT-IR) microspectroscopy centered on spectral regions related to the vibration of–CH3 groups. Image analysis indicated that increased chromatin unpacking promoted by a 4-h-treatment with 1.0 mM VPA persisted for 24 h in the absence of the drug, suggesting the occurrence of DNA demethylation that was confirmed by decreased 5mC immunofluorescence signals. FT-IR spectra of DNA samples from 1 mM or 20 mM VPA-treated cells subjected to a peak fitting analysis of the spectral window for–CH3 stretching vibrations showed decreased vibrations and energy of these groups as a function of the decreased abundance of 5mC induced by increased VPA concentrations. Only the 20 mM-VPA treatment caused an increase in the ratio of -CH3 bending vibrations evaluated at 1375 cm-1 in relation to in-plane vibrations of overall cytosines evaluated at 1492 cm-1. CH3 stretching vibrations showed to be more sensitive than–CH3 bending vibrations, as detected with FT-IR microspectroscopy, for studies aiming to associate vibrational spectroscopy and changes in DNA 5mC abundance. PMID:28114349

  12. The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid-treated MCF-7 breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Zahra Vafaiyan

    2015-07-01

    Conclusion: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

  13. Shear Bond Strength of an Etch-and-rinse Adhesive to Er:YAG Laser- and/or Phosphoric Acid-treated Dentin

    Science.gov (United States)

    Davari, Abdolrahim; Sadeghi, Mostafa; Bakhshi, Hamid

    2013-01-01

    Background and aims. Er:YAG laser irradiation has been claimed to improve the adhesive properties of dentin; therefore, it has been proposed as an alternative to acid etching. The aim of this in vitro study was to investigate the shear bond strength of an etch-and-rinse adhesive system to dentin surfaces following Er:YAG laser and/or phosphoric acid etching. Materials and methods. The roots of 75 sound maxillary premolars were sectioned below the CEJ and the crowns were embedded in auto-polymerizing acrylic resin with the buccal surfaces facing up. The buccal surfaces were ground using a diamond bur and polished until the dentin was exposed; the samples were randomly divided into five groups (n=15) according to the surface treatment: (1) acid etching; (2) laser etching; (3) laser etching followed by acid etching; (4) acid etching followed by laser etching and (5) no acid etching and no laser etching (control group). Composite resin rods (Point 4, Kerr Co) were bonded to treated dentin surfaces with an etch-and-rise adhesive system (Optibond FL, Kerr Co) and light-cured.After storage for two weeks at 37°C and 100% humidity and then thermocycling, bond strength was measured with a Zwick Universal Testing Machine at a crosshead speed of 1 mm/min. Data was analyzed using parametric and non-parametric tests (P<0.05). Results. Mean shear bond strength for acid etching (20.1±1.8 MPa) and acid+laser (15.6±3.5 MPa) groups were significantly higher than those for laser+acid (15.6±3.5 MPa), laser etching (14.1±3.4 MPa) and control (8.1±2.1 MPa) groups. However, there were no significant differences between acid etching and acid+laser groups, and between laser+acid and laser groups. Conclusion. When the cavity is prepared by bur, it is not necessary to etch the dentin surface by Er:YAG laser following acid etching and acid etching after laser etching. PMID:23875083

  14. 乌头碱和甘草酸作用的研究%Study of Interaction of Aconitine and Glycyrrhizic Acid by HPLC

    Institute of Scientific and Technical Information of China (English)

    马鸿雁; 刘小彬; 李楠; 杨明

    2006-01-01

    目的从化学角度揭示附子甘草配伍的机理.方法应用高效液相分析方法,比较了乌头碱单煎、乌头碱甘草酸合煎物质变化的规律.结果乌头碱单煎、乌头碱甘草酸合煎,乌头碱都发生水解;比较单煎、合煎高效液相色谱(HPLC) 结果,甘草酸加速了乌头碱的水解.结论甘草酸加速乌头碱水解是附子甘草配伍减毒机理之一.

  15. An open-label, randomized positron emission tomography (PET) study in healthy male volunteers consisiting of Part A and Part B. Part A: Clinical validation of norepinephrine transporter (NET) PET ligand, (S,S)-[11C]O-methylreboxetine ([11C]MRB) using different doses of oral atomoxetine as NET reuptake inhibitor. Part B: Evaluation of NET occupancy, as measured by [11C]MRB, with multiple dosing regimens of orally administered GSK372475.

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna

    2007-08-31

    Results from human studies with the PET radiotracer (S,S)-[(11)C]O-methyl reboxetine ([(11)C](S,S)-MRB), a ligand targeting the norepinephrine transporter (NET), are reported. Quantification methods were determined from test/retest studies, and sensitivity to pharmacological blockade was tested with different doses of atomoxetine (ATX), a drug that binds to the NET with high affinity (K(i)=2-5 nM). METHODS: Twenty-four male subjects were divided into different groups for serial 90-min PET studies with [(11)C](S,S)-MRB to assess reproducibility and the effect of blocking with different doses of ATX (25, 50 and 100 mg, po). Region-of-interest uptake data and arterial plasma input were analyzed for the distribution volume (DV). Images were normalized to a template, and average parametric images for each group were formed. RESULTS: [(11)C](S,S)-MRB uptake was highest in the thalamus (THL) and the midbrain (MBR) [containing the locus coeruleus (LC)] and lowest for the caudate nucleus (CDT). The CDT, a region with low NET, showed the smallest change on ATX treatment and was used as a reference region for the DV ratio (DVR). The baseline average DVR was 1.48 for both the THL and MBR with lower values for other regions [cerebellum (CB), 1.09; cingulate gyrus (CNG) 1.07]. However, more accurate information about relative densities came from the blocking studies. MBR exhibited greater blocking than THL, indicating a transporter density approximately 40% greater than THL. No relationship was found between DVR change and plasma ATX level. Although the higher dose tended to induce a greater decrease than the lower dose for MBR (average decrease for 25 mg=24+/-7%; 100 mg=31+/-11%), these differences were not significant. The different blocking between MBR (average decrease=28+/- 10%) and THL (average decrease=17+/-10%) given the same baseline DVR indicates that the CDT is not a good measure for non-NET binding in both regions. Threshold analysis of the difference between the average baseline DV image and the average blocked image showed the expected NET distribution with the MBR (LC) and hypothalamus>THL>CNG and CB, as well as a significant change in the supplementary motor area. DVR reproducibility for the different brain regions was approximately 10%, but intersubject variability was large. CONCLUSIONS: The highest density of NETs was found in the MBR where the LC is located, followed by THL, whereas the lowest density was found in basal ganglia (lowest in CDT), consistent with the regional localization of NETs in the nonhuman primate brain. While all three doses of ATX were found to block most regions, no significant differences between doses were found for any region, although the average percent change across subjects of the MBR did correlate with ATX dose. The lack of a dose effect could reflect a low signal-to-noise ratio coupled with the possibility that a sufficient number of transporters were blocked at the lowest dose and further differences could not be detected. However, since the lowest (25 mg) dose is less than the therapeutic doses used in children for the treatment of attention-deficit/hyperactivity disorder ( approximately 1.0 mg/kg/day), this would suggest that there may be additional targets for ATX's therapeutic actions.

  16. ER-Dependent Ca++-mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells.

    Science.gov (United States)

    Lu, Yao-Cheng; Lin, Meng-Liang; Su, Hong-Lin; Chen, Shih-Shun

    2016-02-01

    Release of calcium (Ca(++)) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca(++) release dantrolene and inhibitor of mitochondrial Ca(++) uptake Ru-360, we demonstrated that Ca(++) release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca(++) increase and apoptosis, but did not attenuate the increase in cytosolic Ca(++) level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by treatment with N-acetylcysteine, a ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. Taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca(++)-mediated ROS production.

  17. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Hsin-Cheng Hsu

    2013-01-01

    Full Text Available Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA, which causes intracellular mitogen-activated protein kinase (MAPK signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR and rhynchophylline (RP have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p. to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg, RP (0.25 mg/kg, and valproic acid (VA, 250 mg/kg for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  18. 丙二酸处理硫酸钡填充等规聚丙烯复合材料的结晶性能%Crystallization Properties of Isotactic Polypropylene Composites Filled with Malonic Acid Treated BaSO4

    Institute of Scientific and Technical Information of China (English)

    王龙; 窦强

    2011-01-01

    The melting and crystallization behavior of isotactic polypropylene/barium sulfate composites after isothermal crystallization at 120 ℃ were investigated by means of differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing microscope (PLM). Compared with the untreated filler, the filler treated by malonic-acid facilitates the formation of |3 spherulites in iPP, and the size of the spherulites decreases obviously. At the filler content of 7.5% , the relative (3 form content (Kwaxd) for composite filled with the treated filler reaches the maximum 0.853, while the value is 0.222 for the untreated system. Barium malonate is formed by the chemical reaction between malonic acid and barium sulfate, which serves as the (3 nucleating agent for iPP.%采用差示扫描量热仪、广角X射线衍射仪、偏光显微镜研究了等规聚丙烯/沉淀法硫酸钡复合材料在120℃等温结晶后的熔融和结晶行为.结果表明,与未处理填料体系相比,丙二酸处理硫酸钡有利于聚丙烯中β晶的形成,β晶晶粒明显细化.在7.5%填料含量时,丙二酸处理硫酸钡复合材料的β晶型相对含量(KWAXD)达到最大值0.853,而未处理硫酸钡复合材料的KWAXD仅为0.222.丙二酸处理硫酸钡时,发生化学反应生成的丙二酸钡起到了聚丙烯β晶型成核剂的作用.

  19. 酸浸和焙烧对硅藻土吸附甲醛性能的影响研究%The Influence of Acid-treating and Calcination on Adsorption Properties to Formaldehyde of Diatomite

    Institute of Scientific and Technical Information of China (English)

    王佼; 郑水林

    2011-01-01

    采用酸浸和焙烧法对硅藻土进行了提纯处理,通过SEM和XPS及比表面积测定仪等测试手段对提纯前后的硅藻土进行了表征;并研究了硅藻土对甲醛的吸附性能.结果表明,提纯后的硅藻土SiO2含量显著提高,Fe2O3含量显著下降,比表面积显著增大,对甲醛的吸附性能明显提高.在常温下,影响其吸附的两个因素(甲醛初始量及环境湿度)的最佳范围分别为:甲醛最佳初始浓度为5 μL/m3;最佳环境舱湿度范围为30%RH至40%RH;硅藻土的最佳吸附效率为37.92%.%After diatomite was calcined and treated with sulfuric acid to remove impurity, the purified diatomite was compared with the crude diatomite by SEM, XPS and BET and the adsorption properties to formaldehyde of diatomite. The results showed that the amount of SiO2 increased sharply; meanwhile, the amount of Fe2O3 dropped notably and the specific surface area was enlarged. Therefore, the adsorption capacity was improved. At room temperature, two critical factors, the initial amount of formaldehyde and ambient humidity, have their optimum range. The former should be 5 mL/m3 and the latter should range from 30 % RH to 40 % RH. Then the best adsorption value of diatomite is 37.92 %.

  20. Auricular Electroacupuncture Reduced Inflammation-Related Epilepsy Accompanied by Altered TRPA1, pPKCα, pPKCε, and pERk1/2 Signaling Pathways in Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Yi-Wen Lin

    2014-01-01

    Full Text Available Background. Inflammation is often considered to play a crucial role in epilepsy by affecting iron status and metabolism. In this study, we investigated the curative effect of auricular acupuncture and somatic acupuncture on kainic acid- (KA- induced epilepsy in rats. Methods. We established an epileptic seizure model in rats by KA (12 mg, ip. The 2 Hz electroacupuncture (EA was applied at auricular and applied at Zusanli and Shangjuxu (ST36-ST37 acupoints for 20 min for 3 days/week for 6 weeks beginning on the day following the KA injection. Results. The electrophysiological results indicated that neuron overexcitation occurred in the KA-treated rats. This phenomenon could be reversed among either the auricular EA or ST36-ST37 EA treatment, but not in the sham-control rats. The Western blot results revealed that TRPA1, but not TRPV4, was upregulated by injecting KA and could be attenuated by administering auricular or ST36-ST37 EA, but not in the sham group. In addition, potentiation of TRPA1 was accompanied by increased PKCα and reduced PKCε. Furthermore, pERK1/2, which is indicated in inflammation, was also increased by KA. Furthermore, the aforementioned mechanisms could be reversed by administering auricular EA and could be partially reversed by ST36-ST37 EA. Conclusions. These results indicate a novel mechanism for treating inflammation-associated epilepsy and can be translated into clinical therapy.

  1. Preparation and Characterization of Acid-Treated Multi-Walled Carbon Nanotubes/Poly(p-Phenylene-2,6-Benzoxazole) Composites%酸处理碳纳米管/PBO复合材料的制备与表征

    Institute of Scientific and Technical Information of China (English)

    李霞; 黄玉东

    2007-01-01

    用原位聚合法成功地制备了碳纳米管/聚对苯撑苯并双(噁)唑(PBO)复合材料.用 FT-IR、XPS、SEM和AFM对碳纳米管和所制备的复合材料进行了表征,结果表明,碳纳米管的酸处理效果好,表面含有C-O、COOH等极性官能团; 复合材料中碳纳米管在聚合物基体中分散均匀,两相界面间存在较强的作用力.

  2. Inhibitory effects of citrus fruits on the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid treated with nitrite in the presence of ethanol.

    Science.gov (United States)

    Higashimoto, M; Yamato, H; Kinouchi, T; Ohnishi, Y

    1998-07-31

    It has been shown that the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCCA), a mutagen precursor in soy sauce treated with nitrite, was strongly increased when it was treated with nitrite in the presence of alcohols. We found that the mutagenicity of MTCCA treated with 50 mM nitrite at pH 3, 37 degrees C for 60 min in the presence of 7.5% ethanol was reduced by the addition of citrus fruits sudachi (Citrus sudachi), lemon (C. limon) and yuzu (C. junos), to the reaction mixture. The mutagenicity-reducing activity per weight of flavedos (outer colored portions of peel) of the citrus fruits was considerably higher than that of the juices. The juices of the other citrus fruits commercially available in Japan also had mutagenicity-reducing activity against the nitrite-treated MTCCA. Among the many components of citrus fruits, dietary fibers lignin and pectin showed strong antimutagenic activity in the reaction mixture, suggesting that the mixed fractions of these components including lignin, pectin, D-limonene, naringin, hesperidin, ascorbic acid and citric acid reduce the mutagenicity of MTCCA in the reaction mixture containing nitrite and ethanol.

  3. 超高压同时提取光果甘草中甘草酸和光甘草定的研究%Ultrahigh pressure extraction of glycyrrhizic acid and glabridin from Glycyrrhiza glabra L.

    Institute of Scientific and Technical Information of China (English)

    范丽; 段文娟; 王晓; 方磊; 刘峰

    2013-01-01

    采用超高压技术提取光果甘草中甘草酸、光甘草定两种活性成分,考察提取溶剂、压力、时间和料液比对二者提取率的影响,通过正交试验优化得到超高压最佳提取条件为:60%乙醇作为提取溶剂、提取压力500 MPa、提取时间3 min、料液比1∶40 (g/mL),光果甘草中甘草酸和光甘草定的提取率分别达到49.84 mg/g和1.05 mg/g.超高压提取法同超声提取法、热回流提取法进行比较,结果显示,超高压提取效果明显优于超声提取,同时,超高压提取时间只需1 min,是超声提取的1/30、热回流提取的1/120,缩短了提取时间,提高了工作效率,是一种快速、简单、常温的提取方法.

  4. Simultaneous Determination of Glycyrrhizic Acid and Liquiritin in Zukamu Capsules by HPLC%HPLC同时测定祖卡木颗粒中甘草苷和甘草酸铵含量

    Institute of Scientific and Technical Information of China (English)

    尼加提·阿不来提; 古丽巴哈尔·尼牙孜; 阿力木江·阿卜杜加帕尔

    2015-01-01

    目的 建立高效液相色谱法测定祖卡木颗粒中甘草苷、甘草酸含量的方法.方法 色谱条件:Amethyst-C18色谱柱(250mm×4.6mm,5μm);流动相A为乙腈,B为0.05%磷酸溶液,梯度洗脱;流速1mL/min;检测波长237 nm.结果 色谱峰分离情况良好,甘草苷在0.043 88~0.438 8μg(r=0.999 9)、甘草酸铵在0.04448~~0.4448 μg (r=0.9994)范围内具有良好线性关系.平均加样回收率甘草苷为97.56%(RSD=0.90%),甘草酸铵为100.59%(RSD=1.02%).结论 本方法处理简便,测定结果准确,重复性好,可用于本品的质量控制.

  5. Formulation and preparation of glycyrrhizic acid solid lipid nanoparticles%甘草酸固体脂质纳米粒的处方及制备工艺

    Institute of Scientific and Technical Information of China (English)

    侯君; 周世文

    2008-01-01

    目的 制备甘草酸固体脂质纳米粒(GL-SLN).方法 用旋转蒸发薄膜超声法制备GL-SLN,在单因素考察的基础上,通过正交设计优选该纳米粒的处方及制备工艺,并对优化条件下制备的GL-SLN进行质量评价.结果 制备的GL-SLN大小较均匀,平均粒径为75.8 nm,zeta电位-19.7 mV,载药量8.27%,包封率91.76%.结论 薄膜超声分散法优化工艺制备得到的GL-SLN包封率较高,稳定性好,方法可靠.

  6. Fermented milk supplemented with probiotics and prebiotics can effectively alter the intestinal microbiota and immunity of host animals

    National Research Council Canada - National Science Library

    Wang, S; Zhu, H; Lu, C; Kang, Z; Luo, Y; Feng, L; Lu, X

    2012-01-01

    Fermented milk supplemented with 2 probiotic strains, Bifidobacterium lactis Bi-07 and Lactobacillus acidophilus NCFM, and a prebiotic, isomaltooligosaccharide, was orally administered to 100 healthy...

  7. Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice

    OpenAIRE

    Chung, Sanny S. W.; Wang, Xiangyuan; Roberts, Shelby S.; Stephen M Griffey; Reczek, Peter R.; Wolgemuth, Debra J.

    2011-01-01

    Meeting men's contraceptive needs, orally administered retinoic acid receptor antagonists represent new lead molecules in developing non-hormonal, reversible male contraceptives without adverse side effects.

  8. [Impacts of multicomponent environment on solubility of puerarin in biopharmaceutics classification system of Chinese materia medica].

    Science.gov (United States)

    Hou, Cheng-Bo; Wang, Guo-Peng; Zhang, Qiang; Yang, Wen-Ning; Lv, Bei-Ran; Wei, Li; Dong, Ling

    2014-12-01

    To illustrate the solubility involved in biopharmaceutics classification system of Chinese materia medica (CMMBCS) , the influences of artificial multicomponent environment on solubility were investigated in this study. Mathematical model was built to describe the variation trend of their influence on the solubility of puerarin. Carried out with progressive levels, single component environment: baicalin, berberine and glycyrrhizic acid; double-component environment: baicalin and glycyrrhizic acid, baicalin and berberine and glycyrrhizic acid and berberine; and treble-component environment: baicalin, berberin, glycyrrhizic acid were used to describe the variation tendency of their influences on the solubility of puerarin, respectively. And then, the mathematical regression equation model was established to characterize the solubility of puerarin under multicomponent environment.

  9. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease.

    Science.gov (United States)

    Nagura, Michito; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto; Uchida, Shunya

    2016-12-01

    Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.

  10. 全反式维甲酸在帕金森病大鼠模型中脑神经干细胞移植治疗中的作用%Transplantation of all-trans retinoic acid-treated midbrain-derived neural stem cell for Parkinson's disease in rats

    Institute of Scientific and Technical Information of China (English)

    盛汉松; 周辉; 许尚虞; 林坚; 尹波; 张弩

    2012-01-01

    目的 观察全反式维甲酸(atRA)处理的大鼠中脑神经干细胞(NSCs)移植对帕金森病(PD)模型大鼠的治疗作用.方法 制备PD大鼠模型并将成功模型分为对照组、常规培养中脑NSCs组和atRA处理中脑NSCs组(atRA+NSCs组).动态观察模型大鼠NSCs移植前后的行为学变化,定量分析纹状体多巴胺能神经元表达的变化.结果 atRA+NSCs组与对照组、NSCs组比较,实验动物的行为功能指标均得到有效改善(P<0.05或0.01).atRA+NSCs组与NSCs组大鼠纹状体移植区BrdU标记的酪氨酸羟化酶染色阳性细胞(TH+细胞)分别为(261.2±31.7)、(204.3±25.1)个,差异有统计学意义(P<0.05),而对照组纹状体区没有BrdU标记TH+细胞.结论 atRA在PD大鼠模型中脑NSCs移植治疗中有明显的促进作用,具有潜在的临床应用价值.%To evaluate the transplantation of all-trans retinoic acid (atRA)- treated midbrain-derived neuralstem cell (NSC) for Parkinson's disease (PD) in rats.MethodsThe PD model was induced by injection of 6-hydroxydopamine(6-OHDA) in right striatum in rats. The PD rats were divided into 3 groups: control group, NSC group (transplantation of midbrain-derived NSCs) and atRA+NSCs group (transplantation of atRA- treated NSCs). The rotation scores were assessed before and 1, 4, 8, 12 weeks after transplantation. The dopaminergic neurons in striatum were analyzed quantitatively using immunohis-tochemistry for tyrosine hydroxylaset TH).The apomorphine-induced rotation in atRA+NSCs group was decreased sig-nificantly compared with that of NSCs group (P<0.05) and control group (P<0.01). TH-positive neurons emerged in the striatum of atRA+NSCs and NSCs group was 261.2 ± 31.7 and 204.3 ±25.1 (P<0.05) after transplantation, but no TH-positive neurons were found in the control group.ConclusionAll-trans retinoic acid can enhance the efficacy of NSC transplantation for treatment of PD in rats.

  11. Role of the p70 S6 kinase cascade in neutrophilic differentiation and proliferation of HL-60 cells-a study of transferrin receptor-positive and -negative cells obtained from dimethyl sulfoxide- or retinoic acid-treated HL-60 cells.

    Science.gov (United States)

    Kanayasu-Toyoda, Toshie; Yamaguchi, Teruhide; Oshizawa, Tadashi; Kogi, Mieko; Uchida, Eriko; Hayakawa, Takao

    2002-09-01

    Previously, we suggested that p70 S6 kinase (p70 S6K) plays an important role in the regulation of neutrophilic differentiation of HL-60 cells; this conclusion was based on our analysis of transferrin receptor (Trf-R) positive (Trf-R(+)) and negative (Trf-R(-)) cells that appeared after treatment with dimethyl sulfoxide (Me(2)SO). In this study, we analyzed the upstream of p70 S6K in relation to the differentiation and proliferation of both cell types. The granulocyte colony-stimulating factor (G-CSF)-induced enhancement of phosphatidylinositol 3-kinase (PI3K) activity in Trf-R(+) cells was markedly higher than that in Trf-R(-) cells. Wortmannin, a specific inhibitor of PI3K, partially inhibited G-CSF-induced p70 S6K activity and G-CSF-dependent proliferation, whereas rapamycin, an inhibitor of p70 S6K, completely inhibited these activities. The wortmannin-dependent enhancement of neutrophilic differentiation was similar to that induced by rapamycin. From these results, we conclude that the PI3K/p70 S6K cascade may play an important role in negative regulation of neutrophilic differentiation in HL-60 cells. For the G-CSF-dependent proliferation, however, p70 S6K appears to be a highly important pathway through not only a PI3K-dependent but also possibly an independent cascade.

  12. RP-HPLC determination of glycyrrhizin,glycyrrhizic acid,harpagoside and cinnamic acid in Xuanmai Ganjie granules%RP-HPLC法测定玄麦甘桔颗粒中甘草苷、甘草酸、哈巴俄苷和肉桂酸的含量

    Institute of Scientific and Technical Information of China (English)

    张萍; 郭亚东; 马银海; 马涛; 丁颖洁

    2008-01-01

    目的:建立高效液相色谱法测定玄麦甘桔颗粒中甘草苷、甘草酸、哈巴俄苷、肉桂酸含量.方法:采用LiChrospher RP-C18(250 mm×4.6 mm,5μm)色谱柱,以乙腈-水(含1.0%甲酸)为流动相,梯度洗脱(0~20 min,流动相比例20:80→50:50),流速1 mL·min-1,双波长检测[278 nm(0~18 min,测定甘草苷、哈巴俄苷及肉桂酸),254 nm(18~20 min,测定甘草酸)].结果:甘草苷、甘草酸、哈巴俄苷和肉桂酸分别在0.21~6.30,0.25~7.50,0.10~3.00,0.105~3.15μg范嗣内呈良好的线性关系;平均回收率(n=9)分别为99.6%,99.3%,100.5%,98.9%.结论:该方法简便迅速,准确可靠,重现性好,结果稳定,适合玄麦甘桔颗粒的含量控制.

  13. Determination of Amygdalin, Liquiritin and Glycyrrhizic Acid of Chuanbei Qingfei Syrup by UPLC with Double-wavelength%川贝清肺糖浆中苦杏仁苷、甘草苷和甘草酸的双波长UPLC法测定

    Institute of Scientific and Technical Information of China (English)

    陈建琴

    2015-01-01

    建立了超高效液相色谱法同时测定川贝清肺糖浆中的苦杏仁苷、甘草苷和甘草酸.采用Agilent Eclipse Plus C18色谱柱,以乙腈:0.1%磷酸为流动相,梯度洗脱,双波长切换检测(0~7 min,210 nm测定苦杏仁苷、甘草苷;8~14 min,250 nm测定甘草酸).苦杏仁苷、甘草苷和甘草酸分别在0.9~8.3.0.2~1.7和0.4~3.4μg/ml浓度范围内线性关系良好.平均回收率分别为100.7%、100.8%和99.5%,RSD分别为0.42%、0.56%和0.71%.

  14. 甘草β-香树酯醇合成酶编码区SNP与甘草酸含量的相关性研究%Correlation analysis between single nucleotide polymorphism of β-amyrin synthase and content of glycyrrhizic acid in Glycyrrhiza uralensis

    Institute of Scientific and Technical Information of China (English)

    沈湛云; 刘春生; 王学勇; 呙未; 李贝宁

    2010-01-01

    目的:探讨甘草β-香树酯醇合成酶(β-amyrin synthase,bAS)编码区SNP与甘草酸含量之间的相关性.方法:采用HPLC法测量80株人工栽培甘草的甘草酸含量,采用SAS 9.0软件将80株甘草按照甘草酸含量极显著水平(P<0.000 1)进行分组;采用RT-PCR技术,扩增出甘草bAS编码区序列,运用DNAman分析软件找出该序列的SNP位点,进而分析该位点与甘草酸含量高低的相关性.结果:bAS基因编码区共有94,254 bp 2个突变位点,在94 bp位点发生G/A转换,为错义突变,导致该位点处甘氨酸/天冬氨酸转换,254 bp处发生C/T转换,为同义突变,根据序列变异将所测样品划分成G-T基因型、A-T基因型、G-C基因型和A/G.C基因型.结论:A-T基因型、G/A-C基因型和G-T基因型和高含量甘草酸形成具有显著的相关性.

  15. HPLC同时测定健脾舒胃凝胶中甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵5种成分含量%Determation of Liquiriti, Naringin, Hesperidin, Neohesperidin and Glycyrrhizic Acid Ammonium Salt in Jianpi Shuwei Gel by HPLC

    Institute of Scientific and Technical Information of China (English)

    牛晓静; 鲁静; 段晓颖; 李芬

    2015-01-01

    目的:建立HPLC同时测定健脾舒胃凝胶中甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵5种成分含量控制方法.方法:采用Agilent ZORBAX Eclispse SB-C18色谱柱(4.6 mm ×150 mm,5μm),流动相乙腈-0.05%磷酸水梯度洗脱,流速1.0 mL·min-1,检测波长237 nm(甘草苷、甘草酸铵),283 nm(柚皮苷、橙皮苷、新橙皮苷).结果:根据回归方程,甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵分别在0.1283~0.641 6,1.105 2~5.526,0.225 2~1.1260,1.092~5.460,0.3149~1.5744μg进样量与峰面积之间线性关系良好;5个成分的平均回收率分别为101.47%,99.22%,100.02%,101.64%,97.99%(RSD<3%).结论:该方法简便、准确可靠,重复性好,专属性好,分离效果好,适用于健脾舒胃凝胶的质量控制.

  16. 高效液相色谱法测定凉茶中绿原酸、新橙皮苷、甘草酸的含量%Determination of Chlorogenic Acid, Neohesperidin, Glycyrrhizic Acid in Herbal Tea by High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    曹英华; 贾丽; 夏敏; 范筱京; 王嘉琦

    2010-01-01

    目的:建立凉茶中绿原酸、新橙皮苷、甘草酸的高效液相色谱测定方法.方法:采用ZOEBAX SB-C18柱(4.6×250mm,5 μ-m),以乙腈-0.1%磷酸溶液为流动相,梯度洗脱,流速1.0mL/min;进样量10 μL.结果:绿原酸、新橙皮苷、甘草酸的线性范围均为0.1 0~50mg/L,样品的平均加标回收率范围分别为90.1%~94.0%、97.8%~115%、78.7%~91.9%,相对标准偏差分别为0.60%,1.1 6%、0.67%.该方法操作简便、快速、准确,应用于凉茶中绿原酸、新橙皮苷,甘草酸的分析,取得了较好的结果.

  17. Effect of nalmefene 20 and 80 mg on the corrected QT interval and T-wave morphology: a randomized, double-blind, parallel-group, placebo- and moxifloxacin-controlled, single-centre study

    DEFF Research Database (Denmark)

    Matz, Jørgen; Graff, Claus; Vainio, Petri J;

    2011-01-01

    Nalmefene is an orally administered competitive opioid receptor antagonist targeted at reducing alcohol consumption in alcohol-dependent patients. As part of the regulatory requirements for drug approval, the potential of novel compounds for causing unwanted proarrhythmia should be studied...

  18. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth

    2013-01-01

    BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepir...

  19. Drug: D05150 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available betic; Orally-administered insulin action enhancer to lower the plasma glucose in patients with non-insulin dependent diabetes mellit...us [Type II] peroxisome proliferator-activated receptor (PPAR) gamma modulator [HSA

  20. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide

    Science.gov (United States)

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  1. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application; Availability AGENCY: Food... guidances to industry on ``Bioavailability and Bioequivalence Studies for Orally Administered Drug...

  2. Hepatoprotective and antioxidant effects of Cymbopogon citratus Stapf

    African Journals Online (AJOL)

    Methods: The rats were orally administered CS extract (1000 mg/kg/day) for 30 days prior to induction ... Results: Phytochemical screening of the extract indicate the presence of tannins, flavonoids, and phenolic ..... mouse skin in vivo.

  3. Metabolic profiling of roots of liquorice (Glycyrrhiza glabra) from different geographical areas by ESI/MS/MS and determination of major metabolites by LC-ESI/MS and LC-ESI/MS/MS.

    Science.gov (United States)

    Montoro, Paola; Maldini, Mariateresa; Russo, Mariateresa; Postorino, Santo; Piacente, Sonia; Pizza, Cosimo

    2011-02-20

    Liquid chromatography electrospray mass spectrometry (LC-ESI/MS) has been applied to the full characterization of saponins and phenolics in hydroalcoholic extracts of roots of liquorice (Glycyrrhiza glabra). Relative quantitative analyses of the samples with respect to the phenolic constituents and to a group of saponins related to glycyrrhizic acid were performed using LC-ESI/MS. For the saponin constituents, full scan LC-MS/MS fragmentation of the protonated (positive ion mode) or deprotonated (negative ion mode) molecular species generated diagnostic fragment ions that provided information concerning the triterpene skeleton and the number and nature of the substituents. On the basis of the specific fragmentation of glycyrrhizic acid, an LC-MS/MS method was developed in order to quantify the analyte in the liquorice root samples. Chinese G. glabra roots contained the highest levels of glycyrrhizic acid, followed by those from Italy (Calabria).

  4. Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract

    OpenAIRE

    Chihiro Tohda; Natsuki Nakayama; Fumiyuki Hatanaka; Katsuko Komatsu

    2006-01-01

    We aimed to compare the anti-inflammatory activities of six species of Curcuma drugs using adjuvant arthritis model mice. When orally administered 1 day before the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling and the serum haptoglobin concentration in adjuvant arthritis mice. Also when orally administered 1 day after the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling. Other C...

  5. Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract

    OpenAIRE

    Chihiro Tohda; Natsuki Nakayama; Fumiyuki Hatanaka; Katsuko Komatsu

    2006-01-01

    We aimed to compare the anti-inflammatory activities of six species of Curcuma drugs using adjuvant arthritis model mice. When orally administered 1 day before the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling and the serum haptoglobin concentration in adjuvant arthritis mice. Also when orally administered 1 day after the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling. Other C...

  6. Alternative to antibiotics against Pseudomonas aeruginosa: Effects of Glycyrrhiza glabra on membrane permeability and inhibition of efflux activity and biofilm formation in Pseudomonas aeruginosa and its in vitro time-kill activity.

    Science.gov (United States)

    Chakotiya, Ankita Singh; Tanwar, Ankit; Narula, Alka; Sharma, Rakesh Kumar

    2016-09-01

    The multi-drug resistance offered by Pseudomonas aeruginosa to antibiotics can be attributed towards its propensity to develop biofilm, modification in cell membrane and to efflux antibacterial drugs. The present study explored the activity of Glycyrrhiza glabra and one of its pure compounds, glycyrrhizic acid against P. aeruginosa and their mechanism of action in terms of the effect on membrane permeability, efflux activity, and biofilm formation were determined. Minimum inhibitory concentrations were determined by using broth dilution technique. The minimum bactericidal concentrations were assessed on agar plate. The MIC of the extract and glycyrrhizic acid was found to be 200 and 100 μg ml(-1), respectively. The MBC was found to be 800 and 400 μg ml(-1) in the case of extract and glycyrrhizic acid, respectively. Time -dependent killing efficacy was also estimated. Flowcytometric analysis with staining methods was used to determine the effect of extract and glycyrrhizic acid at 2 × MIC on different physiological parameters and compared it with the standard (antibiotic). The growth of P. aeruginosa was significantly inhibited by extract and the pure compound. The herbal extract and the glycyrrhic acid were also found to effective in targeting the physiological parameters of the bacteria that involve cell membrane permeabilization, efflux activity, and biofilm formation. This study reports the antipseudomonal action of Glycyrrhiza glabra and one of its compound and provides insight into their mode of action.

  7. Proteomic Analysis of the Rat Ovary Following Chronic Low-Dose Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

    NARCIS (Netherlands)

    Chen, Xi; Ma, Xiao-ming; Ma, Shi-wei; Coenraads, Pieter-Jan; Zhang, Chun-mei; Liu, Jing; Zhao, Li-jun; Sun, Min; Tang, Nai-jun

    2009-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (2

  8. Nanoparticle formulation of a poorly soluble cannabinoid receptor 1 antagonist improves absorption by rat and human intestine

    NARCIS (Netherlands)

    Siissalo, Sanna; De Waard, Hans; De Jager, Marina H.; Hayeshi, Rose; Frijlink, Henderik W.; Hinrichs, Wouter L.J.; Dinter-Heidorn, Heike; Van Dam, Annie; Proost, Johannes H.; Groothuis, Geny M.M.; De Graaf, Inge A.M.

    2013-01-01

    The inclusion of nanoparticles dispersed in a hydrophilic matrix is one of the formulation strategies to improve the bioavailability of orally administered Biopharmaceutics Classification System (BCS) class II and IV drugs by increasing their dissolution rate in the intestine. To confirm that the in

  9. Nanoparticle formulation of a poorly soluble cannabinoid receptor 1 antagonist improves absorption by rat and human intestine

    NARCIS (Netherlands)

    Siissalo, Sanna; De Waard, Hans; De Jager, Marina H.; Hayeshi, Rose; Frijlink, Henderik W.; Hinrichs, Wouter L.J.; Dinter-Heidorn, Heike; Van Dam, Annie; Proost, Johannes H.; Groothuis, Geny M.M.; De Graaf, Inge A.M.

    2013-01-01

    The inclusion of nanoparticles dispersed in a hydrophilic matrix is one of the formulation strategies to improve the bioavailability of orally administered Biopharmaceutics Classification System (BCS) class II and IV drugs by increasing their dissolution rate in the intestine. To confirm that the in

  10. Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis

    DEFF Research Database (Denmark)

    Petersen, Andreas Munk; Mirsepasi, Hengameh; Halkjær, Sofie Ingdam

    2014-01-01

    BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add...

  11. Tc-99m-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours

    NARCIS (Netherlands)

    Bakker, M; Van der Graaf, WTA; Piers, DA; Franssen, EJF; Groen, HJM; Smit, EF; Kool, W; Hollema, H; Muller, EA; de Vries, EGE

    1999-01-01

    Background: Our aim was to determine the value of 99mTc-Sestamibi scanning as functional detection method of P-glycoprotein (Pgp) blockade by PSC 833 in solid tumour patients. Patients and methods: Day 1 and day 4 after 2,200 mg orally administered PSC 833 the tumour area was scanned after intraveno

  12. Effect of nalmefene 20 and 80 mg on the corrected QT interval and T-wave morphology

    DEFF Research Database (Denmark)

    Matz, Jørgen; Graff, Claus; Vainio, Petri J.

    2011-01-01

    Nalmefene is an orally administered competitive opioid receptor antagonist targeted at reducing alcohol consumption in alcohol-dependent patients. As part of the regulatory requirements for drug approval, the potential of novel compounds for causing unwanted proarrhythmia should be studied...... in a thoroughly designed clinical QT/corrected QT (QTc) study (International Conference on Harmonisation [ICH] E14 guideline)....

  13. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    Science.gov (United States)

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  14. Effects of Green Tea Extract on Learning, Memory, Behavior and Acetylcholinesterase Activity in Young and Old Male Rats

    Science.gov (United States)

    Kaur, Tranum; Pathak, C. M.; Pandhi, P.; Khanduja, K. L.

    2008-01-01

    Objective: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. Methods: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.…

  15. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats

    DEFF Research Database (Denmark)

    Kristensen, Sara Hestehave; Munro, Gordon; Pedersen, Tina Brønnum

    2017-01-01

    . In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing...

  16. Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy

    DEFF Research Database (Denmark)

    Sheetz, Matthew J; Aiello, Lloyd Paul; Shahri, Nazila

    2011-01-01

    The PKC-DRS2 was a Phase 3, randomized, double-masked, placebo (PBO)-controlled, 3-year study of the effect of 32 mg/day of ruboxistaurin (RBX), an orally administered protein kinase C inhibitor, on vision loss in patients with moderate to severe nonproliferative diabetic retinopathy. Ruboxistaur...

  17. 21 CFR 522.1150 - Hydrochlorothiazide injection.

    Science.gov (United States)

    2010-04-01

    ... onset of diuresis, treatment may be continued with an orally administered maintenance dose. (2) Indications for use. For use in cattle as an aid in the treatment of postparturient udder edema.1 1 These... during treatment and for 72 hours (6 milkings) after the latest treatment must not be used for food...

  18. 21 CFR 310.529 - Drug products containing active ingredients offered over-the-counter (OTC) for oral use as insect...

    Science.gov (United States)

    2010-04-01

    ... offered over-the-counter (OTC) for oral use as insect repellents. 310.529 Section 310.529 Food and Drugs... ingredients offered over-the-counter (OTC) for oral use as insect repellents. (a) Thiamine hydrochloride... insect repellent (an orally administered drug product intended to keep insects away). There is a lack...

  19. Oral administration of deuterium-labelled polyamines to sucking rat pups : luminal uptake, metabolic fate and effects on gastrointestinal maturation

    NARCIS (Netherlands)

    Dorhout, B; van Faassen, A; van Beusekom, C M; Kingma, A W; de Hoog, E; Nagel, G T; Karrenbeld, A; Boersma, E R; Muskiet, F A

    1997-01-01

    Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuter

  20. Prevention and control of iodine deficiency: studies on the efficacy of oral iodized oil.

    NARCIS (Netherlands)

    Furnée, C.A.

    1994-01-01

    Iodized oil, either injected or given orally, is the major alternative to iodized salt for controlling iodine deficiency. Oral administration has considerable advantages despite its shorter duration of effect. Little information is available on factors which influence the effect of orally administer

  1. Lactulose as a marker of intestinal barrier function in pigs after weaning

    NARCIS (Netherlands)

    Wijtten, P.J.A.; Verstijnen, J.J.; Kempen, van T.A.T.G.; Perdok, H.B.; Gort, G.; Verstegen, M.W.A.

    2011-01-01

    Intestinal barrier function in pigs after weaning is almost exclusively determined in terminal experiments with Ussing chambers. Alternatively, the recovery in urine of orally administered lactulose can be used to assess intestinal permeability in living animals. This experiment was designed to

  2. Effects of Green Tea Extract on Learning, Memory, Behavior and Acetylcholinesterase Activity in Young and Old Male Rats

    Science.gov (United States)

    Kaur, Tranum; Pathak, C. M.; Pandhi, P.; Khanduja, K. L.

    2008-01-01

    Objective: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. Methods: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.…

  3. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  4. Candida albicans septicemia in a premature infant successfully treated with oral fluconazole

    DEFF Research Database (Denmark)

    Bodé, S; Pedersen-Bjergaard, Lars; Hjelt, K

    1992-01-01

    A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days. Dosage was 5 mg/kg/day. No side effects were seen. Fluconazole may present a major progress in treatment of invasive C. albicans infections in...... in neonatology....

  5. Examining triclosan-induced potentiation of the estrogen uterotrophic effect

    Science.gov (United States)

    Triclosan (TCS), a widely used antibacterial, has been shown to be an endocrine disruptor. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats orally administered 3 μg/kg EE and TCS (2 to 18 mg/kg) in the utero...

  6. Therapeutic combination of sildenafil and iloprost in a preterm neonate with pulmonary hypertension.

    Science.gov (United States)

    Gürakan, Berkan; Kayiran, Petek; Oztürk, Nilüfer; Kayiran, Sinan Mahir; Dindar, Aygün

    2011-06-01

    While new pharmacological approaches have been demonstrated to effectively manage PH in adults, few reports have addressed PH treatment in neonates and infants. This case report describes the successful management of severe PH secondary to bronchopulmonary dysplasia, respiratory syncytial virus infection, and hypoxia in a preterm 4-month-old with the long-term use of orally administered sildenafil and inhaled iloprost.

  7. Development of an oral dosage form of capecitabine with modified release characteristics

    NARCIS (Netherlands)

    Meulenaar, J

    2013-01-01

    Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of a.o. metastatic breast, gastric and colorectal cancer and is commercially available as an immediate release tablet (Xeloda®, Roche). Capecitabine is a pre-pro-drug that is enzymatically converted into 5-fluorourac

  8. Bacillus subtilis Spores Germinate in the Chicken Gastrointestinal Tract▿

    OpenAIRE

    Stephen T Cartman; La Ragione, Roberto M.; Woodward, Martin J.

    2008-01-01

    A number of poultry probiotics contain bacterial spores. In this study, orally administered spores of Bacillus subtilis germinated in the gastrointestinal (GI) tracts of chicks. Furthermore, 20 h after spores were administered, vegetative cells outnumbered spores throughout the GI tract. This demonstrates that spore-based probiotics may function in this host through metabolically active mechanisms.

  9. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    CSIR Research Space (South Africa)

    Mandiwana, V

    2015-09-01

    Full Text Available the biodistribution of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([(sup153)Sm]Sm(sub2)O(sub3)) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear...

  10. Safety profile of Hoodia gordonii extract: Mouse prenatal developmental toxicity study

    NARCIS (Netherlands)

    Dent, M.P.; Wolterbeek, A.P.M.; Russell, P.J.; Bradford, R.

    2012-01-01

    Hoodia gordonii extract (0, 5, 15 or 50. mg/kg body weight/day, n= 24 mice/group) was orally administered by gavage to female CD-1 mice from gestation days 5-17. On gestation day 18 the females were euthanized and examined. Treatment at 50. mg/kg/day caused a marked reduction in feed intake and body

  11. Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

    Science.gov (United States)

    Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

  12. Lactulose as a marker of intestinal barrier function in pigs after weaning

    NARCIS (Netherlands)

    Wijtten, P.J.A.; Verstijnen, J.J.; Kempen, van T.A.T.G.; Perdok, H.B.; Gort, G.; Verstegen, M.W.A.

    2011-01-01

    Intestinal barrier function in pigs after weaning is almost exclusively determined in terminal experiments with Ussing chambers. Alternatively, the recovery in urine of orally administered lactulose can be used to assess intestinal permeability in living animals. This experiment was designed to stud

  13. Safety profile of Hoodia gordonii extract: Rabbit prenatal developmental toxicity study

    NARCIS (Netherlands)

    Dent, M.P.; Wolterbeek, A.P.M.; Russell, P.J.; Bradford, R.

    2012-01-01

    Hoodia gordonii extract was orally administered by gavage to groups of 22 female New Zealand white rabbits from day 3-28 after mating at doses of 0 (control), 3, 6 or 12. mg/kg bodyweight/day. These doses were reached by a dose escalation phase between days 3 and 7 after mating. As well as a vehicle

  14. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2016-01-01

    The enterocyte monolayer in the intestinal membrane impacts on the bioavailability (BA) of many orally administered active pharmaceutical ingredients (APIs). The monolayer expresses a multitude of membrane transporters belonging to the solute carrier (SLC) and ATP-binding cassette (ABC) families ...

  15. Oral antibiotics for perforated appendicitis is not recommended

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Gögenur, Ismail; Rosenberg, Jacob

    2010-01-01

    In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this pap...

  16. Candida albicans septicemia in a premature infant successfully treated with oral fluconazole

    DEFF Research Database (Denmark)

    Bodé, S; Pedersen-Bjergaard, Lars; Hjelt, K

    1992-01-01

    A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days. Dosage was 5 mg/kg/day. No side effects were seen. Fluconazole may present a major progress in treatment of invasive C. albicans infections...

  17. Efficacy of a new pulmonary cyclosporine a powder formulation for prevention of transplant rejection in rats

    NARCIS (Netherlands)

    Zijlstra, Gerrit S.; Wolting, Joske; Prop, Jochum; Petersen, Arjen H.; Hinrichs, Wouter L.J.; Uges, Donald R.A.; Kerstjens, Huib A.M.; van der Bij, Wim; Frijlink, Henderik W.

    2009-01-01

    Background: The aim of this pilot study was to determine the pharmacokinetics of cyclosporine A powder for inhalation (iCsA) and its rejection prevention efficacy in an experimental lung transplantation model in rats. Methods: Single-dose pharmacokinetics (10 mg/kg) of pulmonary and orally administe

  18. Morphological Awareness Uniquely Predicts Young Children's Chinese Character Recognition.

    Science.gov (United States)

    McBride-Chang, Catherine; Shu, Hua; Zhou, Aibao; Wat, Chun Pong; Wagner, Richard K.

    2003-01-01

    Two unique measures of morphological awareness were orally administered to kindergarten and 2nd-grade Hong Kong Chinese children. Both tasks of morphological awareness predicted unique variance in Chinese character recognition in these children, after controlling for age, phonological awareness, speeded naming, speed of processing, and vocabulary.…

  19. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial

    NARCIS (Netherlands)

    Brose, M.S.; Nutting, C.M.; Jarzab, B.; Elisei, R.; Siena, S. Di; Bastholt, L.; Fouchardiere, C. de la; Pacini, F.; Paschke, R.; Shong, Y.K.; Sherman, S.I.; Smit, J.W.; Chung, J.; Kappeler, C.; Pena, C.; Molnar, I.; Schlumberger, M.J.

    2014-01-01

    BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the treatm

  20. The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats

    DEFF Research Database (Denmark)

    Madsen, Jeanette Lund; Kroghsbo, Stine; Madsen, Charlotte Bernhard;

    2014-01-01

    This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens......, indicating that the structural characteristics of proteins may heavily affect the induced antibody response....

  1. Effect of ruboxistaurin in patients with diabetic macular edema : Thirty-month results of the randomized PKC-DMES clinical trial

    NARCIS (Netherlands)

    Aiello, Lloyd Paul; Ai, Everett; Aiello, Lloyd M.; Anand, Rajiv; Blumenkranz, Mark; Boyer, David; Brucker, Alexander J.; Chandler, Thomas; Chong, Lawrence; Connor, Thomas; Danis, Ron; Dehning, Doug; Dodson, Paul; Eaton, Alexander; Faber, David; Finkelstein, Dan; Forrester, John V.; Frank, Robert N.; Garcia, Charles; Gardner, Thomas W.; Gehrs, Karen M.; Goodart, Roy A.; Gottlieb, Justin; Greven, Craig M.; Guyer, David R.; Hainsworth, Dean; Hooper, Philip; Jackson, Willliam E.; Kinyoun, James L.; Kipnes, Mark; Klein, Michael L.; Kohner, Eva M.; Kuppermann, Baruch; Lewis, Hilel; Li, Helen K.; Lund-Anderson, Henrik; Ma, Colin; Martin, Daniel F.; Orellana, Juan; Paden, Philip Y.; Polak, Bettine; Ross, Stuart A.; Sharuk, George; Singerman, Lawrence J.; Smiddy, William E.; Trese, Michael; Tweeten, James P.; Vine, Andrew; Vora, Jiten; Wolffenbuttel, Bruce

    2007-01-01

    Objective: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME). 1 Design: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally ( 4, 16, or 32 mg/d)

  2. Hereditary epidermolytic palmoplantar keratoderma (Vörner type). Report of a familial case and review of the literature.

    Science.gov (United States)

    Kanitakis, J; Tsoitis, G; Kanitakis, C

    1987-09-01

    A recent familial case of hereditary epidermolytic palmoplantar keratoderma (Vörner type) that was treated with orally administered etretinate is reported herein. A review of the literature with regard to the clinical, genetic, and laboratory features of this rare genodermatosis is also presented.

  3. PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES ON VAGINALLY ADMINISTERED LEVONORGESTREL

    Institute of Scientific and Technical Information of China (English)

    HEChang-Hai; XUJian-Qiu; ZHUYue-Hua; SHIYong-En

    1989-01-01

    Comparative studies on pharmacokinetics of vaginally and orally administered levonorgestrel (LNG) tablet (Postinor) in one single dose containing 0,75mg LNG were performed. The pharmacokinetics of LNG and its effects on ovarian functions werealso studied after repeated vaginal administration.

  4. Effect of ruboxistaurin in patients with diabetic macular edema : Thirty-month results of the randomized PKC-DMES clinical trial

    NARCIS (Netherlands)

    Aiello, Lloyd Paul; Ai, Everett; Aiello, Lloyd M.; Anand, Rajiv; Blumenkranz, Mark; Boyer, David; Brucker, Alexander J.; Chandler, Thomas; Chong, Lawrence; Connor, Thomas; Danis, Ron; Dehning, Doug; Dodson, Paul; Eaton, Alexander; Faber, David; Finkelstein, Dan; Forrester, John V.; Frank, Robert N.; Garcia, Charles; Gardner, Thomas W.; Gehrs, Karen M.; Goodart, Roy A.; Gottlieb, Justin; Greven, Craig M.; Guyer, David R.; Hainsworth, Dean; Hooper, Philip; Jackson, Willliam E.; Kinyoun, James L.; Kipnes, Mark; Klein, Michael L.; Kohner, Eva M.; Kuppermann, Baruch; Lewis, Hilel; Li, Helen K.; Lund-Anderson, Henrik; Ma, Colin; Martin, Daniel F.; Orellana, Juan; Paden, Philip Y.; Polak, Bettine; Ross, Stuart A.; Sharuk, George; Singerman, Lawrence J.; Smiddy, William E.; Trese, Michael; Tweeten, James P.; Vine, Andrew; Vora, Jiten; Wolffenbuttel, Bruce

    Objective: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME). 1 Design: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally ( 4, 16, or 32 mg/d)

  5. Comparative morphophysiological evaluation of the testis of adult ...

    African Journals Online (AJOL)

    olayemitoyin

    Wistar rats fed low protein-energy diet and dosed with aqueous extracts ... Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria. ... energy intake may influence the efficacy of orally administered aqueous extracts of C. ... The diets and drinking water ..... [Article in Chinese].

  6. A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis.

    Science.gov (United States)

    Ilan, Yaron; Gingis-Velitski, Svetlana; Ben Ya'aco, Ami; Shabbat, Yehudit; Zolotarov, Lidya; Almon, Einat; Shaaltiel, Yoseph

    2017-03-01

    The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain.

  7. The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole: the ERY-PAO Study

    NARCIS (Netherlands)

    Mitrov-Winkelmolen, Lieke; van Buul-Gast, Marie Christine W; Swank, Dingeman J.; Overdiek, Hans W P M; van Schaik, Ron H N; Touw, Daan J.

    2016-01-01

    Background Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass (RYGB) surgery in obese patients are limited and inconclusive. As it is difficult to predict changes in absorption, studies on frequently used drugs in this population are necessary. Acetylsalicylic aci

  8. The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole : the ERY-PAO Study

    NARCIS (Netherlands)

    Mitrov-Winkelmolen, Lieke; van Buul-Gast, Marie-Christine W.; Swank, Dingeman J.; Overdiek, Hans W. P. M.; van Schaik, Ron H. N.; Touw, Daan J.

    2016-01-01

    Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass (RYGB) surgery in obese patients are limited and inconclusive. As it is difficult to predict changes in absorption, studies on frequently used drugs in this population are necessary. Acetylsalicylic acid (ASA) and

  9. Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

    DEFF Research Database (Denmark)

    Hadrup, Niels; Lam, Henrik Rye

    2014-01-01

    Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin...

  10. A pilot study on the pharmacokinetics of potato glycoalkaloids in healthy volunteers

    NARCIS (Netherlands)

    Rompelberg CJM; Sips AJAM; Twillert K van; Mensinga Tj; Top HJ van den; Meulenbelt J; Egmont HP van; LBM; NVIC; ARO

    2001-01-01

    To improve risk assessment of the potato glycoalkaloids (GAs) alfa-solanine and alfa-chaconine, a study on pharmacokinetics of orally administered GAs in humans is planned to be carried out at the National Institute of Public Health and the Environment (RIVM). The limited information on toxicity in

  11. Viscous Food Matrix Influences Absorption and Excretion but Not Metabolism of Blackcurrant Anthocyanins in Rats

    NARCIS (Netherlands)

    Walton, M.C.; Hendriks, W.H.; Broomfield, A.M.; McGhie, T.K.

    2009-01-01

    The aim of the present study was to investigate the effect of a simultaneous intake of food and anthocyanins (ACNs) on ACN absorption, metabolism, and excretion. Blackcurrant ACNs (BcACNs) were dissolved in water with or without the addition of oatmeal and orally administered to rats, providing appr

  12. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  13. Effect of ruboxistaurin in patients with diabetic macular edema : Thirty-month results of the randomized PKC-DMES clinical trial

    NARCIS (Netherlands)

    Aiello, Lloyd Paul; Ai, Everett; Aiello, Lloyd M.; Anand, Rajiv; Blumenkranz, Mark; Boyer, David; Brucker, Alexander J.; Chandler, Thomas; Chong, Lawrence; Connor, Thomas; Danis, Ron; Dehning, Doug; Dodson, Paul; Eaton, Alexander; Faber, David; Finkelstein, Dan; Forrester, John V.; Frank, Robert N.; Garcia, Charles; Gardner, Thomas W.; Gehrs, Karen M.; Goodart, Roy A.; Gottlieb, Justin; Greven, Craig M.; Guyer, David R.; Hainsworth, Dean; Hooper, Philip; Jackson, Willliam E.; Kinyoun, James L.; Kipnes, Mark; Klein, Michael L.; Kohner, Eva M.; Kuppermann, Baruch; Lewis, Hilel; Li, Helen K.; Lund-Anderson, Henrik; Ma, Colin; Martin, Daniel F.; Orellana, Juan; Paden, Philip Y.; Polak, Bettine; Ross, Stuart A.; Sharuk, George; Singerman, Lawrence J.; Smiddy, William E.; Trese, Michael; Tweeten, James P.; Vine, Andrew; Vora, Jiten; Wolffenbuttel, Bruce

    2007-01-01

    Objective: To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME). 1 Design: Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally ( 4, 16, or 32 mg/d)

  14. [Effect of Tongfeng trace elements nutrient balance agent on growth, physiological characteristics and content of active constituents of Glycyrrhiza uralensis].

    Science.gov (United States)

    Wang, Dan; Wan, Chunyang; Wang, Wenquan; Gu, Bin; Li, Jiajia; Wang, Wenjie; Hou, Songnian; Han, Zhongwen

    2011-08-01

    To investigate the effects of Tongfeng trace elements nutrient balance agent on the various growth indicators, physiological indicators, and the contents of liquiritin and glycyrrhizic acid in one-year old Glycyrrhiza uralensis. The plants of G. uralensis growing in Chifeng of Inner Mongolia and medicinal garden of Beijing University of Chinese Medicine were fertilized for two times, respectively. The photosynthetic physiological indicators were measured by LI-6400 photosynthetic instrument. The pigments and antioxidase activities of the leaves were determined. Then contents of liquiritin and glycyrrhizic acid in the plants were determined by HPLC. The application of this trace element nutrient balance agent could significantly improve the height, chla and chlb, and the photosynthetic physiology indicator such as P(n), C(i), and G(s). Similarly, it could significantly increase the fresh weight of shoots and dry weight of the roots. Compared with control block (CK), the fertilizer which was diluted by 300 times (T(1)) and 600 times (T(2)) significantly increased the content of glycyrrhizic acid by 24.72% and 20. 23%. There was significant difference between different treatments (P elements nutrient balance agent could promote growth, physiology and the content of active constituents of G. uralensis, especially the effect of T(1) was superior to T(2).

  15. Lack of effects of astemizole on vestibular ocular reflex, motion sickness, and cognitive performance in man

    Science.gov (United States)

    Kohl, Randall L.; Homick, Jerry L.; Cintron, Nitza; Calkins, Dick S.

    1987-01-01

    Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following one week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads to the conclusion that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.

  16. A New Approach to the Oral Administration of Insulin and Other Peptide Drugs

    Science.gov (United States)

    Saffran, Murray; Sudesh Kumar, G.; Savariar, Celin; Burnham, Jeffrey C.; Williams, Frederick; Neckers, Douglas C.

    1986-09-01

    The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

  17. Hepatoprotective effects of pycnogenol in a rat model of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2012-10-01

    Oxidative stress is considered as a mechanism of hepatocellular injury in non-alcoholic steatohepatitis (NASH). Pycnogenol (PYC) is the natural plant extract from the bark of Pinus pinaster Aiton. and has potent antioxidant activities. We studied the protective effect of PYC on excessive fat accumulation in the liver fed a methionine-choline deficient (MCD) high-fat diet for 6 weeks. Pycnogenol (10 mg/kg body weight) was orally administered for 5 weeks. At the end of the experiment, blood and liver samples were collected and assessed for effects of PYC by histopathological and biochemical analyses. Histopathological analyses of liver tissues stained with Azan-Mallory showed hepatic macrovesicular steatosis and fibrosis in MCD-fed rats. Supplementation of PYC prevented this effect. Pycnogenol treatment significantly decreased the liver triglyceride and serum alanine amino transferase levels. Our results indicated that orally administered PYC may serve to prevent NASH-induced liver damage.

  18. Pycnogenol ameliorates depression-like behavior in repeated corticosterone-induced depression mice model.

    Science.gov (United States)

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2014-01-01

    Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC) is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT-) treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL) was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity.

  19. Pycnogenol Ameliorates Depression-Like Behavior in Repeated Corticosterone-Induced Depression Mice Model

    Directory of Open Access Journals (Sweden)

    Lin Mei

    2014-01-01

    Full Text Available Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT- treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity.

  20. Interaction of Peptide Transporter 1 With D-Glucose and L-Glutamic Acid; Possible Involvement of Taste Receptors.

    Science.gov (United States)

    Arakawa, Hiroshi; Ohmachi, Taichi; Ichiba, Kiko; Kamioka, Hiroki; Tomono, Takumi; Kanagawa, Masahiko; Idota, Yoko; Hatano, Yasuko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates.

  1. Royal Jelly Facilitates Restoration of the Cognitive Ability in Trimethyltin-Intoxicated Mice

    Directory of Open Access Journals (Sweden)

    Noriko Hattori

    2011-01-01

    Full Text Available Trimethyltin (TMT is a toxic organotin compound that induces acute neuronal death selectively in the hippocampal dentate gyrus (DG followed by cognition impairment; however the TMT-injured hippocampal DG itself is reported to regenerate the neuronal cell layer through rapid enhancement of neurogenesis. Neural stem/progenitor cells (NS/NPCs are present in the adult hippocampal DG, and generate neurons that can function for the cognition ability. Therefore, we investigated whether royal jelly (RJ stimulates the regenerating processes of the TMT-injured hippocampal DG, and found that orally administered RJ significantly increased the number of DG granule cells and simultaneously improved the cognitive impairment. Furthermore, we have already shown that RJ facilitates neurogenesis of cultured NS/NPCs. These present results, taken together with previous observations, suggest that the orally administered RJ may be a promising avenue for ameliorating neuronal function by regenerating hippocampal granule cells that function in the cognition process.

  2. Early pharmaceutical profiling to predict oral drug absorption

    DEFF Research Database (Denmark)

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup

    2014-01-01

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmac......Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary...... and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties...

  3. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis

    OpenAIRE

    Inomata, Minoru; Kamio, Koichiro; Azuma, Arata; Matsuda, Kuniko; Kokuho, Nariaki; Miura, Yukiko; Hayashi, Hiroki; Nei, Takahito; Fujita, Kazue; Saito, Yoshinobu; Gemma, Akihiko

    2014-01-01

    Background Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether pirfenidone inhibits fibrocyte pool size in the lungs of bleomycin-treated mice. Methods Bleomycin (100 mg/kg) was infused with osmotic pumps into C57BL/6 mice, and pirfenidone (300 mg/kg/day) was orally administered d...

  4. Formulation, development and evaluation of patient friendly dosage forms of metformin, Part-I: Orally disintegrating tablets

    OpenAIRE

    Mohapatra Ashutosh; Parikh Rajesh; Gohel Mukesh

    2008-01-01

    Metformin hydrochloride is an orally administered antihyperglycemic agent, used in the management of non-insulin-dependant (type-2) diabetes mellitus. Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly and pediatrics. Unfortunately, a high percentage of patients suffering from type-2 diabetes are elderly people showing dysphagia. In this study, orally disintegrating tablets were prepared using direct compression and wet granulation method. First, the ta...

  5. Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

    OpenAIRE

    Jong-Jin Kim; Jina Choi; Mi-Kyung Lee; Kyung-Yun Kang; Man-Jeong Paik; Sung-Kee Jo; Uhee Jung; Hae-Ran Park; Sung-Tae Yee

    2014-01-01

    HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozo...

  6. Central depressant and nootropic effects of daytime melatonin in mice

    OpenAIRE

    Onaolapo, Olakunle J; Adejoke Y. Onaolapo; Abiola, Akanni A; Lillian, Eniafe A

    2014-01-01

    Background Effects of orally administered daytime melatonin on novelty induced behaviors and spatial working memory in mice were evaluated using the open field, the Y maze and the radial arm maze. Purpose To ascertain the possible nootropic and/or central excitatory or inhibitory effects of daytime oral melatonin in mice. Methods Adult male mice from our colony, assigned to three and four groups for open field tests and memory tests respectively were given vehicle (normal saline), a standard ...

  7. Oral Administration of Surface-Deacetylated Chitin Nanofibers and Chitosan Inhibit 5-Fluorouracil-Induced Intestinal Mucositis in Mice

    Science.gov (United States)

    Koizumi, Ryo; Azuma, Kazuo; Izawa, Hironori; Morimoto, Minoru; Ochi, Kosuke; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2017-01-01

    This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs. PMID:28134832

  8. Comparative speed of kill of sarolaner (Simparica™) and afoxolaner (NexGard®) against induced infestations of Rhipicephalus sanguineus s.l. on dogs

    OpenAIRE

    Six, Robert H.; Young, David R.; Holzmer, Susan J.; Mahabir, Sean P.

    2016-01-01

    Background The brown dog tick, Rhipicephalus sanguineus sensu lato, commonly infests dogs globally, is the major vector of the pathogen that causes canine monocytic ehrlichiosis and also transmits Babesia vogeli. A rapid speed of kill of a parasiticide is essential to reduce the direct deleterious effects of tick infestation and the risk of tick-borne pathogen transmission. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica™), against R. sanguineus...

  9. Comparative speed of kill of sarolaner (Simparica™) and afoxolaner (NexGard®) against induced infestations of Amblyomma americanum on dogs

    OpenAIRE

    Six, Robert H.; Everett, William R.; Chapin, Sara; Mahabir, Sean P.

    2016-01-01

    Background The lone star tick, Amblyomma americanum, infests dogs and cats in North America and is the vector of the pathogens that cause monocytic and granulocytic ehrlichiosis in dogs and humans. A parasiticide’s speed of kill is important to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of transmission of tick-borne pathogens. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica™ chewa...

  10. Comparative speed of kill of sarolaner (Simparica™) and afoxolaner (NexGard®) against induced infestations of Ctenocephalides felis on dogs

    OpenAIRE

    Six, Robert H.; Liebenberg, Julian; Honsberger, Nicole A.; Mahabir, Sean P.

    2016-01-01

    Background Fleas are the most common ectoparasite infesting dogs globally. The many possible sequellae of infestation include: direct discomfort; allergic reactions; and the transmission of pathogens. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea infestation cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiti...

  11. Hypoglycemic effect of Opuntia cactus.

    Science.gov (United States)

    Ibañez-Camacho, R; Roman-Ramos, R

    1979-01-01

    Nopal (Opuntia sp.) has been traditionally used by the Mexican population for the treatment of diabetes mellitus. The purpose of this work is to describe effects produced by directly liquified nopal and extracts from this plant in healthy and pancreatectomized rabbits. Preliminary results allow us to conclude that Opuntia streptacantha, Lemaire, has hypoglycemic properties when orally administered, in animals with experimentally induced diabetes as well as in healthy ones with physiologic hyperglycemia.

  12. Effect of Chitin Extraction Processes on Residual Antimicrobials in Shrimp Shells

    OpenAIRE

    2012-01-01

    The present study examined the influences of industrial chitin extraction processes on the residual oxytetracycline (OTC) and oxolinic acid (OA) in shrimp carapaces and shells. The drugs were orally administered by catheter to the kuruma shrimp (Penaeus japonicus) and vannamei shrimp (Penaeus vannamei). The shrimps were sampled at 6-h post-dosing and their carapaces and shells were collected and used as raw material in the chitin extraction. Residua...

  13. Feline immunodeficiency virus can be experimentally transmitted via milk during acute maternal infection.

    OpenAIRE

    Sellon, R K; Jordan, H L; Kennedy-Stoskopf, S; Tompkins, M B; Tompkins, W A

    1994-01-01

    Postnatal transmission of feline immunodeficiency virus (FIV) in neonates nursed by acutely infected mothers and infection resulting from oral inoculation of kittens with FIV were evaluated. Ten of 16 kittens nursed by four queens with FIV infection established immediately postpartum developed FIV infection. Five of 11 neonates orally administered cell-free FIV culture supernatant developed FIV infection. Kittens that developed FIV infection had greater proportions of CD4+ and Pan-T+ lymphocy...

  14. Variable efficacy of calcium carbonate tablets.

    Science.gov (United States)

    Kobrin, S M; Goldstein, S J; Shangraw, R F; Raja, R M

    1989-12-01

    Orally administered calcium carbonate tablets are commonly prescribed as a calcium supplement and for their phosphate-binding effects in renal failure patients. Two cases are reported in which a commercially available brand of calcium carbonate tablets appeared to be ineffective. Formal investigation of the bioavailability of this product revealed it to have impaired disintegration and dissolution and a lack of clinical efficacy. Recommendations that will enable physicians to avoid prescribing and pharmacists to avoid dispensing ineffective calcium carbonate tablets are proposed.

  15. Role of IKKalpha and STAT3 in the Emergence of Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2013-06-01

    androgen-deprived tumor stroma we orally administered a DNA vaccine encoding FAP that is specifically delivered to secondary lymphoid tissues by a...molecular pathology 87, 189-194. Gabbiani, G. (2003). The myofibroblast in wound healing and fibrocontractive diseases. The Journal of pathology 200, 500...affecting wound healing. Journal of dental research 89, 219-229. Higgins, D. F., Biju, M. P., Akai, Y., Wutz, A., Johnson, R. S., and Haase, V. H

  16. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping

    OpenAIRE

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2015-01-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for...

  17. Metformin-induced regulation of the intestinal D-glucose transporters.

    OpenAIRE

    Sakar, Yassine; Meddah, Bouchra; El Abbes Faouzi, Moulay; Cherrah, Yahia; Bado, André; Ducroc, Robert

    2010-01-01

    International audience; Metformin is an orally administered drug that lowers blood glucose and improves insulin sensitivity in patients with non insulin-dependent diabetes. Although the antihyperglycemic effect of metformin has been extensively studied, its cellular mechanism(s) of action (including the effect on enterocyte) remains to be defined. This study was designed to examine the effect of metformin on glucose transporters in enterocyte. Na(+)-dependent glucose transporter-1 (SGLT-1) ac...

  18. In vivo imaging of Lactococcus lactis, Lactobacillus plantarum and Escherichiacoli expressing infrared fluorescent protein in mice

    OpenAIRE

    Berlec, Aleš; Štrukelj, Borut; Završnik, Janja; Turk, Boris; Butinar, Miha

    2016-01-01

    Background In vivo imaging of orally administered lactic acid bacteria (LAB) and commensal bacteria in mice is shown to provide information on the spatial and temporal distribution of bacteria in the gastrointestinal tract. The bacteria can be detected and monitored using bioluminescence or near-infrared fluorescence. Results Fluorescence imaging of bacteria was established by expressing the infrared fluorescent protein IRFP713 in Lactococcus lactis, Lactobacillus plantarum and Escherichia co...

  19. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

    OpenAIRE

    Mustonen Katja; Niemi Anneli; Raekallio Marja; Heinonen Mari; Peltoniemi Olli AT; Palviainen Mari; Siven Mia; Peltoniemi Marikki; Vainio Outi

    2012-01-01

    Abstract Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers betwee...

  20. Lack of experimental evidence to support mcr-1-positive escherichia coli strain selection during oral administration of colistin at recommended and higher dose given by gavage in weaned piglets.

    Science.gov (United States)

    Viel, Alexis; Henri, Jérôme; Perrin-Guyomard, Agnès; Laroche, Julian; Couet, William; Grégoire, Nicolas; Laurentie, Michel

    2017-06-28

    In this study, we assessed the selective effect of colistin orally administered to healthy weaned piglets harbouring an intestinal mcr-1-positive Escherichia coli strain. Maximum recommended dose and a higher dose often used in European pig farms were given by gavage. No selection of the mcr-1-positive strain was observed in our controlled conditions whatever the dose. Further investigations in real farming conditions seem necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  1. Efficacy of Orally Delivered Cochleates Containing Amphotericin B in a Murine Model of Aspergillosis

    OpenAIRE

    Delmas, G.; Park, S.; Chen, Z W; Tan, F.; Kashiwazaki, R.; Zarif, L.; Perlin, D. S.

    2002-01-01

    Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.

  2. Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis.

    Science.gov (United States)

    Delmas, G; Park, S; Chen, Z W; Tan, F; Kashiwazaki, R; Zarif, L; Perlin, D S

    2002-08-01

    Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.

  3. Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine

    OpenAIRE

    Nobrega, Franklin L.; Ana Rita Costa; Santos,José F.; Siliakus, Melvin F.; van Lent, Jan W. M.; Kengen, Servé W. M.; Joana Azeredo; Kluskens, Leon D.

    2016-01-01

    Orally administered phages to control zoonotic pathogens face important challenges, mainly related to the hostile conditions found in the gastrointestinal tract (GIT). These include temperature, salinity and primarily pH, which is exceptionally low in certain compartments. Phage survival under these conditions can be jeopardized and undermine treatment. Strategies like encapsulation have been attempted with relative success, but are typically complex and require several optimization steps. He...

  4. Hepatoprotective activity of Tephrosia purpurea against arsenic induced toxicity in rats

    OpenAIRE

    Ravuri Halley Gora; Sushma Lalita Baxla; Priscilla Kerketta; Subhasree Patnaik; Birendra Kumar Roy

    2014-01-01

    Aim: The present study was conducted to evaluate the hepatoprotective activity of Tephrosia purpurea (TP) against sodium arsenite (NaAsO2) induced sub-acute toxicity in rats. Materials and Methods: Twenty four wistar albino rats of either sex were randomly divided into three groups. Group II and III were orally administered with sodium arsenite (10 mg/kg) daily in drinking water for 28 days. Additionally Group III was orally treated with hydro-alcoholic extract of Tephrosia purpurea (TP) ...

  5. Sexual dysfunction in dialysis patients: does vitamin D deficiency have a role?

    OpenAIRE

    Kidir, Veysel; Altuntas, Atila; Inal, Salih; Akpinar, Abdullah; Orhan, Hikmet; Sezer, Mehmet Tugrul

    2015-01-01

    Introduction: Sexual dysfunction and vitamin D deficiency are highly prevalent in dialysis patients. Low levels of vitamin D have been linked to many diseases. To the best of our knowledge, the relationship between vitamin D and sexual dysfunction in dialysis patients has not been previously reported in the literature. Materials and methods: Cholecalciferol, 50,000 IU/week, was orally administered to 37 dialysis patients with vitamin D insufficiency for 3 months followed by dosage of 10,000 I...

  6. Highly enantioselective synthesis of non-natural aliphatic α-amino acids via asymmetric hydrogenation.

    Science.gov (United States)

    Ji, Jianjian; Chen, Caiyou; Cai, Jiayu; Wang, Xinrui; Zhang, Kai; Shi, Liyang; Lv, Hui; Zhang, Xumu

    2015-07-28

    By employing a rhodium-Duanphos complex as the catalyst, β-alkyl (Z)-N-acetyldehydroamino esters were smoothly hydrogenated in a highly efficient and enantioselective way. Excellent enantioselectivities together with excellent yields were achieved for a series of substrates. An efficient approach for the synthesis of the intermediate of the orally administered anti-diabetic drugs Alogliptin and Linagliptin in the DPP-4 inhibitor class was also developed.

  7. Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain

    OpenAIRE

    Impellizzeri, Daniela; Bruschetta, Giuseppe; Cordaro, Marika; Crupi, Rosalia; Siracusa, Rosalba; Esposito, Emanuela; Cuzzocrea, Salvatore

    2014-01-01

    Background The fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory effica...

  8. Health Risk Assessment of Consuming Deer from Aberdeen Proving Ground, Maryland. Report and Appendices A-D

    Science.gov (United States)

    1995-05-01

    Health 7:668-67-* Baxley, M.N; Hood, R.^.; Vedel, G.C.; Harrison , W.P.; Szczech, G.M. 1981. Prenatal toxicity of orally administered sodium...1972. Teratogenic effects of sodium arsenate in mice. Arch. Er.»iron. Health 24:62-65. 18 Hood, RJX; Harrison , WJP. 1982. Effects of...Revista de la Facultad de Medicina de Torreon 12:16. (Cited in ATSDR, 1989). Schaumourg, HA. 1980. Failure to produce arsenic neurotoxicity in

  9. Managing patients taking novel oral anticoagulants (NOAs) in dentistry: a discussion paper on clinical implications

    OpenAIRE

    Costantinides, Fulvia; Rizzo, Roberto; Pascazio, Lorenzo; Maglione, Michele

    2016-01-01

    Background The aim of this paper is to contribute to the discussion on how to approach patients taking new orally administered anticoagulants (NOAs) dabigatran etexilate (a direct thrombin inhibitor), rivaroxaban and apixaban (factor Xa inhibitors), before, during and after dental treatment in light of the more recent knowledges. Discussion In dentistry and oral surgery, the major concerns in treatment of patients taking direct thrombin inhibitors and factor Xa inhibitors is the risk of haemo...

  10. Thyroid Alterations in Porcine After Prolonged Exposure to Cold or Heat

    Science.gov (United States)

    1992-01-01

    deiodination at the 5’ position, so T4 levels act as a buffer for rapid T3 changes. No significant differences in thyroid hormone levels between cold and...intracellular thyroid hormone alterations. These studies demonstrated a rise in serum clearance of orally administered triiodothyronine (T 3 ), T3 production...brown fat by the sympathetic nervous system, under permissive control of thyroid hormone (2), but with a different peripheral profile during prolonged

  11. Effect of bitter melon (Momordica charantia Linn) fruit juice on blood prolactin level and histological change of mammary gland in lactating mice

    OpenAIRE

    Ampa Luangpirom; Watchara Kourchampa; Pichet Somsapt

    2013-01-01

    Breastfeeding has nowadays been promoted. Meanwhile, lactation insufficiency is a significant problem. Thus, herbs for promoting milk are interesting. In Thai local wisdom, Momordica charantia Linn is claimed as a galactagogue. Experiments were performed in lactating mice with 6 litters each and metoclopramide (2 mg/100 g BW), a hyperprolactinemia inducing drug, was used as a reference drug. The drug and M. charantia fruit juice (400 and 600 mg/100 g BW) were orally administered d...

  12. Removal of internally deposited gold by 2,3-dimercaptopropane sodium sulphonate (Dimaval).

    OpenAIRE

    Gabard, B.

    1980-01-01

    1 Orally administered 2,3-dimercaptopropane sodium sulphonate (DMPS, Dimaval) reduced the concentration of gold in rats treated with Auro-Detoxin and increased the urinary excretion of the metal. 2 In a long-term experiment, DMPS decreased significantly the concentration of gold in the kidneys and in the skin and increased it in plasma. 3 DMPS appears to be of interest as a possible antidote to gold, which could replace the more toxic 2,3-dimercaptopropanol (BAL).

  13. RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability.

    OpenAIRE

    1982-01-01

    1 In a double-blind, placebo controlled study, the efficacy of Ro 15-1788, a new benzodiazepine antagonist, in blocking the cognitive, psychomotor and subjective effects of diazepam, was investigated in a group of six healthy male volunteers. 2 The central effects of orally administered diazepam (40 mg) were most pronounced 1 h after dosing and persisted for 9 h with decreasing severity. 3 Concurrent oral administration of Ro 15-1788 (200 mg) completely prevented the impairment in cognitive a...

  14. Synthesis of Clarithromycin Using Protective Technique of Total Silylation

    Institute of Scientific and Technical Information of China (English)

    FENG Yu-Ling; SUN Jing-Guo

    2003-01-01

    @@ Clarithromycin, 6- O-methylerythromycin A (CAM), is a semisynthetic macrolide antibiotic of 6 which exhibits strong antibacterial activity toward a wide range of bacteria inclusive of gram positive bacteria, some gram negative bacteria, anaerobic bacteria, Mycoplasma, Chlamidia and Helicobacter pylori, and because of its high stability in the acidic environment of the stomach, it can be orally administered to treat respiratory organ diseases, and also to prevent recurrence of ulcer when used in a combination with other medicines.

  15. Studies on fenbendazole for treating lung and intestinal parasites in horses and donkeys.

    Science.gov (United States)

    Urch, D L; Allen, W R

    1980-04-01

    The efficacy of orally administered fenbendazole on lung and intestinal parasitism in equids was investigated in a mixed herd of pony mares, jenny donkeys and foals. A single dose of 7.5 mg fenbendazole/kg body weight effectively removed intestinal parasites from the ponies, donkeys and foals, but higher doses and repeated treatments failed to eliminate lungworm infections in donkeys. The finding of eosinophilia proved useful in detecting lungworm infections in donkeys.

  16. Sodium chlorate reduces presence of Escherichia coli in feces of lambs and ewes managed in shed-lambing systems

    Science.gov (United States)

    Our objective was to establish doses of orally-administered NaClO3 that reduced presence of generic Escherichia coli in intestines of ewes and neonatal lambs managed in a shed-lambing system. Neonatal lambs (n = 32; age = 7.1 ± 1.2 d; BW = 6.8 ± 1.0 kg) and yearling ewes (n = 44; BW = 74.8 ± 5.6 kg)...

  17. ▼ Apremilast for psoriasis and psoriatic arthritis.

    Science.gov (United States)

    2015-09-01

    ▼ Apremilast (Otezla - Celgene Europe Ltd.) is a novel orally administered immunomodulatory medicine licensed for the treatment of plaque psoriasis and psoriatic arthritis. The company suggests that it has demonstrated proven and durable efficacy in both conditions and has a favourable safety profile with no requirement for drug-specific pre-screening or ongoing laboratory monitoring. Here we review the evidence on the safety and efficacy of apremilast in the management of psoriasis and psoriatic arthritis.

  18. Eight-year survival after advanced gastric cancer treated with S-1 followed by surgery

    Institute of Scientific and Technical Information of China (English)

    Susumu; Hijioka; Keisho; Chin; Yasuyuki; Seto; Noriko; Yamamoto; Kiyohiko; Hatake

    2010-01-01

    We report a case of advanced gastric cancer, with cervical, axillary, and abdominal paraaortic lymph node metastases, that was successfully treated with chemotherapy and surgery. The disease was initially considered unresectable, and the patient was treated with orally administered S-1. Chemotherapy was effective, and all lymph node metastases disappeared after 6 courses. After 27 mo of chemotherapy, the patient underwent curative surgery, with subtotal gastrectomy and lymph node dissection. Histopathologic...

  19. A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

    OpenAIRE

    Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun

    2013-01-01

    Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prosta...

  20. The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam.

    OpenAIRE

    1987-01-01

    The effect of cimetidine on the single dose pharmacokinetics of orally administered clobazam and N-desmethylclobazam (NDMC) was studied in volunteers. Cimetidine inhibited the elimination of both clobazam and NDMC and inhibited the rate of formation of NDMC from clobazam. The increase in the AUC for NDMC generated from clobazam was relatively greater than that for clobazam itself. This suggests that NDMC elimination is inhibited to a relatively greater extent than clobazam elimination. The in...

  1. Ethyl Acetate Fraction of Amomum xanthioides Exerts Antihepatofibrotic Actions via the Regulation of Fibrogenic Cytokines in a Dimethylnitrosamine-Induced Rat Model

    OpenAIRE

    Sung-Bae Lee; Hyeong-Geug Kim; Hyo-Seon Kim; Jin-Seok Lee; Hwi-Jin Im; Won-Yong Kim; Chang-Gue Son

    2016-01-01

    Amomum xanthioides has been traditionally used to treat diverse digestive system disorders in the Asian countries. We investigated antihepatofibrotic effects of ethyl acetate fraction of Amomum xanthioides (EFAX). Liver fibrosis is induced by dimethylnitrosamine (DMN) injection (intraperitoneally, 10 mg/kg of DMN for 4 weeks to Sprague-Dawley rats). EFAX (25 or 50 mg/kg), silymarin (50 mg/kg), or distilled water was orally administered every day. The DMN injection drastically altered body and...

  2. Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy

    Science.gov (United States)

    2010-01-01

    the course of their disease (5) represents another significant source of exposure as normal tissues are subjected to radiation injury. Those charged...received thermal burns concurrent with radiation injury, (26, 35). At the Chernobyl reactor meltdown, 10% of 237 victims exposed to radiation received...injections, orally administered drugs, and perhaps subcutaneous injections (39) may be the most complex treatments available to mass casualty victims

  3. Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

    OpenAIRE

    Jong-Jin Kim; Jina Choi; Mi-Kyung Lee; Kyung-Yun Kang; Man-Jeong Paik; Sung-Kee Jo; Uhee Jung; Hae-Ran Park; Sung-Tae Yee

    2014-01-01

    HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozo...

  4. Information Search of Toxic-Free Ammunition

    Science.gov (United States)

    1994-04-01

    exposure has been with bismuth compounds used in medical procedures, such as the treatment of ulcers and other gastro-intestinal disorders. There is...necessitate frequent cleaning in order to ensure that toxic effluents do not runoff into ground water . The second option is to design service and/or...bone, and liver. (Ballou 1960). Kays (1968) who orally administered amonium tun•state and sodium tungstata in 3•OH to rats reported the concentration

  5. Exploring the link between gastric motility and intragastric drug distribution in man.

    Science.gov (United States)

    Van Den Abeele, Jens; Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

    2017-03-01

    In drug development, the stomach is often considered to be a simple, one-compartmental organ, a waiting room for transfer of an orally administered dosage form to the duodenum. However, factors such as gastric acidity and hydrodynamics in the gastric environment may influence drug disposition. Although a link between gastrointestinal drug behaviour and gastric motility has often been hypothesized, they have not been simultaneously investigated in humans yet. In this proof-of-concept study, the combination of a well-established intraluminal sampling technique with high-resolution manometric measurements in the gastrointestinal tract was evaluated. This new combination of in vivo techniques proved to be feasible from a practical point of view and yielded valuable additional information regarding intraluminal drug behaviour. As a first application, the link between fasted state gastric motility and (in)homogeneous distribution of an orally administered drug in the stomach was investigated in healthy subjects. To this end, drug concentrations were measured in different regions of the stomach after oral administration of a commercially available drug product (Gabbroral®, 250mg paromomycin) during a specific period of gastric contractile activity. A clear trend towards better mixing of an orally administered drug with gastric contents was observed when dosed in the presence of gastric contractions, resulting in a more homogeneous distribution of the drug throughout the stomach compared to dosing in the absence of gastric contractions.

  6. Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats.

    Science.gov (United States)

    Matsumoto, Takashi; Matsubara, Yousuke; Mizuhara, Yasuharu; Sekiguchi, Kyoji; Koseki, Junichi; Tsuchiya, Kazuaki; Nishimura, Hiroaki; Watanabe, Junko; Kaneko, Atsushi; Maemura, Kazuya; Hattori, Tomohisa; Kase, Yoshio

    2015-09-30

    Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.

  7. Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats

    Directory of Open Access Journals (Sweden)

    Takashi Matsumoto

    2015-09-01

    Full Text Available Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT, a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.

  8. Low direct cytotoxicity of nabumetone on gastric mucosal cells.

    Science.gov (United States)

    Arai, Yasuhiro; Tanaka, Ken-Ichiro; Ushijima, Hironori; Tomisato, Wataru; Tsutsumi, Shinji; Aburaya, Mayuko; Hoshino, Tatsuya; Yokomizo, Kazumi; Suzuki, Keitarou; Katsu, Takashi; Tsuchiya, Tomofusa; Mizushima, Tohru

    2005-09-01

    Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for clinical purposes because they are not harmful to the gastrointestinal mucosa. We recently showed that NSAIDs have direct cytotoxicity in NSAID-induced gastric lesions. We show here that under conditions where the NSAIDs indomethacin and celecoxib clearly induce cell death, an NSAID prodrug, nabumetone, and its active metabolite 6-methoxy-2-naphthylacetic acid (6MNA), did not have such effects. Moreover, nabumetone and 6MNA exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We recently reported that when an orally administered NSAID was used in combination with a low dose of intravenously administered indomethacin, the severity of gastric lesions produced in rats depended on the cytotoxicity of the orally administered NSAID. Using a similar protocol, we show here that gastric lesions were produced when the orally administered NSAID was celecoxib, but not when nabumetone was used. We thus propose that the low direct cytotoxicity of nabumetone observed in vitro is maintained in vivo, and that the use of nabumetone does not harm the gastric mucosa.

  9. Primed Activation of Macrophages by Oral Administration of Lipopolysaccharide Derived from Pantoea agglomerans.

    Science.gov (United States)

    Inagawa, Hiroyuki; Kobayashi, Yutaro; Kohchi, Chie; Zhang, Ran; Shibasaki, Yasuhiro; Soma, Gen-Ichiro

    2016-01-01

    Bacterial lipopolysaccharide (LPS) is involved in the activation of the innate immune responses on monocytes/macrophages in vitro, and by intravenous injection. Although small quantities of LPS are usually found in traditional Chinese medicines, vegetables and fruits, the mode of action of orally administered LPS is still unclear. LPS derived from Pantoea agglomerans (LPSp) was orally administered to C3H/HeN or C3H/HeJ mice ad libitum. The LPSp treatment enhanced phagocytosis by resident peritoneal macrophages of C3H/HeN mice but not of C3H/HeJ mice. This activation can be defined as primed activation because no augmentation of inflammatory cytokines production was detected. LPSp in peritoneal fluid was detected and successfully quantified. Moreover, the LPSp reduced the expression of avian reticuloendotheliosis viral oncogene-related B (RelB) in the macrophages without degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (IκBα). Orally administered LPSp can reach the peritoneum, and enhance phagocytosis via Toll-like receptor 4 signaling pathway in resident peritoneal macrophages. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Primed Immune Responses Triggered by Ingested Bacteria Lead to Systemic Infection Tolerance in Silkworms.

    Directory of Open Access Journals (Sweden)

    Atsushi Miyashita

    Full Text Available In the present study, we examined whether microorganisms collaterally ingested by insects with their food activate the innate immune system to confer systemic resistance against subsequent bacterial invasion. Silkworms orally administered heat-killed Pseudomonas aeruginosa cells showed resistance against intra-hemolymph infection by P. aeruginosa. Oral administration of peptidoglycans, cell wall components of P. aeruginosa, conferred protective effects against P. aeruginosa infection, whereas oral administration of lipopolysaccharides, bacterial surface components, did not. In silkworms orally administered heat-killed P. aeruginosa cells, P. aeruginosa growth was inhibited in the hemolymph, and mRNA amounts of the antimicrobial peptides cecropin A and moricin were increased in the hemocytes and fat body. Furthermore, the amount of paralytic peptide, an insect cytokine that activates innate immune reactions, was increased in the hemolymph of silkworms orally administered heat-killed P. aeruginosa cells. These findings suggest that insects sense bacteria present in their food by peptidoglycan recognition, which activates systemic immune reactions to defend the insects against a second round of infection.

  11. [Determination of contents of amygdalin in traditional and granular decoctions of Maxingshigan decoction by HPLC].

    Science.gov (United States)

    Wu, Kong-yun; Liang, Guang-yi; He, Zhu-ying; Jin, Feng-yun; Li, Xing; Feng, Hua

    2007-09-01

    To determine the contents of amygdalin in traditional and granular decoctions of Maxingshigan decoction. The determination was carried out by HPLC with an ODS column and a mobile phase of water-methanol (23:77) at 215 nm. The content of amygdalin in traditional decoction of Maxingshigan Decoction was 17.74 mg/g and 24.80 mg/g in granular one. The content of glycyrrhizic acid in traditional decoction of Maxingshigan decoction is obviously higher than that in granular one.

  12. The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: update to the study protocol and detailed statistical analysis plan (SAP).

    Science.gov (United States)

    Boland, Fiona; Quirke, Michael; Gannon, Brenda; Plunkett, Sinead; Hayden, John; McCourt, John; O'Sullivan, Ronan; Eustace, Joseph; Deasy, Conor; Wakai, Abel

    2017-08-24

    Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Patients will be randomised to either orally administered flucloxacillin 500 mg four times daily and placebo or orally administered 500 mg of flucloxacillin four times daily and phenoxymethylpenicillin 500 mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin

  13. Glycyrrhetinic acid and its derivatives in infectious diseases

    Directory of Open Access Journals (Sweden)

    Langer Dominik

    2016-09-01

    Full Text Available Introduction. Licorice or liquorice (Glycyrrhiza glabra, Leguminosae is a perennial plant naturally occurring or cultivated in Europe and Asia. It was appreciated by many ancient cultures, and was employed within Arabic medicine and (beginning in the Middle Ages in Europe folk medicine as a remedy for many diseases. Currently, the sweet flavoured root of this plant – Radix Glycyrrhizae (Liquirtiae, is widely taken for the treating of various upper respiratory tract diseases, as well as for gastric ulcer disease. It is also utilized as a sweetening and flavouring agent in the food, tobacco and pharmacy industries. The main active ingredient of liquorice is the triterpenoid saponin, glycyrrhizin, which is a mixture of calcium, magnesium and potassium salts of glycyrrhizic acid (GA. Glycyrrhizic acid is composed of an aglycone, that is 18β-glycyrrhetinic acid (GE, and a D-glucuronic acid dimer. The aim of this review is to discuss some aspects of the activity of glycyrrhetinic acid and its derivatives in infectious diseases.

  14. [Effect of multicomponent environment on intestinal permeability of puerarin in biopharmaceutics classification system of Chinese materia medica].

    Science.gov (United States)

    Liu, Yang; Wang, Gang; Dong, Ling; Tang, Ming-Min; Zhu, Mei-Ling; Dong, Hong-Huant; Hou, Cheng-Bo

    2014-12-01

    The evaluation of permeability in biopharmaceutics classification system of Chinese materia medica (CMMBCS) requires multicomponent as a whole in order to conduct research, even in the study of a specific component, should also be put in the multicomponent environment. Based on this principle, the high content components in Gegen Qinlian decoction were used as multicomponent environmental impact factors in the experiment, and the relevant parameters of intestinal permeability about puerarin were measured with using in situ single-pass intestinal perfusion model, to investigate and evaluate the intestinal permeability of puerarin with other high content components. The experimental results showed that different proportions of baicalin, glycyrrhizic acid and berberine had certain influence on intestinal permeability of puerarin, and glycyrrhizic acid could significantly inhibit the intestinal absorption of puerarin, moreover, high concentration of berberine could promote the absorption of puerarin. The research results indicated that the important research ideas of permeability evaluation in biopharmaceutics classification system of Chinese materia medica with fully considering the effects of other ingredients in multicomponent environment.

  15. Evaluation of the value of near infrared (NIR) spectromicroscopy for the analysis of glycyrrizhic acid in licorice.

    Science.gov (United States)

    Wu, Zhi-Sheng; Zhou, Lu-Wei; Dai, Sheng-Yun; Shi, Xin-Yuan; Qiao, Yan-Jiang

    2015-04-01

    It has been reported that hyperspectral data could be employed to qualitatively elucidate the spatial composition of tablets of Chinese medicinal plants. To gain more insights into this technology, a quantitative profile provided by near infrared (NIR) spectromicroscopy was further studied by determining the glycyrrhizic acid content in licorice, Glycyrrhiza uralensis. Thirty-nine samples from twenty-four different origins were analyzed using NIR spectromicroscopy. Partial least squares, interval partial least square (iPLS), and least squares support vector regression (LS-SVR) methods were used to develop linear and non-linear calibration models, with optimal calibration parameters (number of interval numbers, kernel parameter, etc.) being explored. The root mean square error of prediction (RMSEP) and the coefficient of determination (R(2)) of the iPLS model were 0.717 7% and 0.936 1 in the prediction set, respectively. The RMSEP and R(2) of LS-SVR model were 0.515 5% and 0.951 4 in the prediction set, respectively. These results demonstrated that the glycyrrhizic acid content in licorice could barely be analyzed by NIR spectromicroscopy, suggesting that good quality quantitative data are difficult to obtain from microscopic NIR spectra for complicated Chinese medicinal plant materials.

  16. Combination of the advantages of chromatographic methods based on active components for the quality evaluation of licorice.

    Science.gov (United States)

    Liu, Xujia; Li, Qing; Lv, Chunxiao; Du, Yiyang; Xu, Huarong; Wang, Di; Li, Mingxiao; Li, Bohui; Li, Jing; Bi, Kaishun

    2015-12-01

    A rapid, improved and comprehensive method including high-performance thin-layer chromatography, fingerprint technology and single standard to determine multiple components was developed and validated for the quality evaluation of licorice. In this study, a newly developed high-performance thin-layer chromatography method was first used for authentication of licorice, which achieved simultaneous identification of multiple bands including five bands for known bioactive components by comparing their retention factor values and colors with the standards. For fingerprint analysis, 8 of 16 common peaks were identified. Simultaneously, similarity analysis which showed very similar patterns and hierarchical clustering analysis were performed to discriminate and classify the 27 batches of samples. Additionally, the single standard to determine multiple components method was first successfully achieved to quantify the eight important active markers in licorice including liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquritin, neoisoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid. The easily available glycyrrhizic acid was selected as the reference substance to calculate relative response factors. Compared with the normal external standard method, this alternative method can be used to determine the multiple indices effectively and accurately. The validation result showed that the developed method was specific, accurate, precise, robust and reliable for the overall quality assessment of licorice.

  17. Correlation analysis between the rate of respiration in the root and the active components in licorice (Glycyrrhiza uralensis).

    Science.gov (United States)

    Guo, Peijun; Sun, Zhirong; Liu, Wenlan; Chen, Long; DU, Yuan; Wei, Xinxin

    2014-01-01

    The aim of this study was to investigate the correlation between root respiration and the percentage of active components in licorice (Glycyrrhiza uralensis Fisch.), in order to provide a foundation for the regulation and modulation of the quality of G. uralensis. Respiration efflux of annual and biennial G. uralensis was determined using a Li-7000 CO2/H2O analyzer. The root systems were scanned at a resolution of 3,000 dpi using an Epson Expression 10000XL scanner. Root growth was determined by analyzing the scanned images using WinRHIZO version Pro2007d software and the rate of respiration in the root was subsequently calculated. In addition, the percentages of the five major active components in licorice, glycyrrhizic acid, glycyrrhizin, isoliquiritin, liquiritigenin and isoliquiritigenin, were detected using high-performance liquid chromatography (HPLC). The correlation between the root respiration and the percentage of the active components was investigated. Significant seasonal changes were observed in the rates of respiration of first and zero-class roots. In annual and biennial G. uralensis, the maximum and minimum values for rate of respiration were present in July (Pactive components and the rate of respiration were -0.304 (glycyrrhizin), -0.129 (liquiritigenin), -0.441 (glycyrrhizic acid; Pactive components in G. uralensis may be beneficial to ensuring the quality of cultivated G. uralensis.

  18. PAIN REDUCING IN ICTERIC NEEWBORNS WHILE VENIPUNCTURING: COMPARISON OF LOCAL ANESTHETIC CREAM WITH ORALLY GLUCOSE

    Directory of Open Access Journals (Sweden)

    M. Noori Shadkam M.H. Lotfi

    2008-04-01

    Full Text Available A number of studies has shown that orally administered sweet-tasting solutions reduce signs of pain during painful procedures. The local anesthetic cream EMLA has recently been shown to be safe for use in neonates. The present study aimed to compare the pain-reducing effect of EMLA cream with that of orally administered glucose during venipuncturing in newborns in Yazd city. A randomized, controlled, double-blind Clinical trial was done on the 220 newborns undergoing venipuncture for clinical purposes. One hundred- six of the newborns received EMLA on the skin and orally administered placebo (sterile water and 114 received orally glucose 30% and placebo (Vit A+D on the skin. Symptoms associated with pain while venipuncturing measured by Neonatal/ Infant pain scale (NIPS and crying time were compared between two groups. There were no differences in background variables between the 2 groups. The results showed that the NIPS scores were significantly lower in the glucose group (Median: 2 compared with the EMLA group (Median: 3 (P=.000. The duration of crying in the first 2 minutes was significantly lower in the glucose group (Median: 2sec than in EMLA group (Median: 9sec (P<.01. 12.3% and 29.2% of neonates in glucose and EMLA groups had NIPS above 3 respectively where the observed difference was found to be statistically significant (P<.05. Our study showed that compared with EMLA cream, orally administration glucose can be more effective, tolerable and convenient in reducing of pain resulting from venipuncturing in neonatal period.

  19. Comparative Pharmacokinetics of the Organophosphorus Insecticide Chlorpyrifos and its Major Metabolites Diethylphosphate, Diethylthiophosphate and 3,5,6-Trichloro-2-pyridinol in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Busby, Andrea L; Campbell, James A; Needham, Larry L; Barr, Dana

    2007-07-31

    Abstract Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual’s contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with their kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140 μmol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1-3 h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72 h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, ~50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22 ± 3 μmol) > DETP (14 ± 2 μmol) > DEP (1.4 ± 0.7 μmol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.

  20. E. coli infection modulates the pharmacokinetics of oral enrofloxacin by targeting P-glycoprotein in small intestine and CYP450 3A in liver and kidney of broilers.

    Science.gov (United States)

    Guo, Mengjie; Sun, Yong; Zhang, Yu; Bughio, Shamsuddin; Dai, Xiaohua; Ren, Weilong; Wang, Liping

    2014-01-01

    P-glycoprotein (P-gp) expression determines the absorption, distribution, metabolism and excretion of many drugs in the body. Also, up-regulation of P-gp acts as a defense mechanism against acute inflammation. This study examined expression levels of abcb1 mRNA and localization of P-gp protein in the liver, kidney, duodenum, jejunum and ileum in healthy and E. coli infected broilers by real time RT-PCR and immunohistochemistry. Meanwhile, pharmacokinetics of orally administered enrofloxacin was also investigated in healthy and infected broilers by HPLC. The results indicated that E. coli infection up-regulated expression of abcb1 mRNA levels significantly in the kidney, jejunum and ileum (P0.05). However, the expression level of CYP 3A37 mRNA were observed significantly decreased only in liver and kidney of E. coli infected broilers (Pabsorption of orally administered enrofloxacin, significantly decreased Cmax (0.34 vs 0.98 µg mL(-1), P = 0.000) and AUC0-12h (4.37 vs 8.88 µg mL(-1) h, P = 0.042) of enrofloxacin, but increased Tmax (8.32 vs 3.28 h, P = 0.040), T1/2a(2.66 vs 1.64 h(-1), P = 0.050) and V/F (26.7 vs 5.2 L, P = 0.040). Treatment with verapamil, an inhibitor of P-gp, significantly improved the absorption of enrofloxacin in both healthy and infected broilers. The results suggest that the E. coli infection induces intestine P-gp expression, altering the absorption of orally administered enrofloxacin in broilers.

  1. E. coli infection modulates the pharmacokinetics of oral enrofloxacin by targeting P-glycoprotein in small intestine and CYP450 3A in liver and kidney of broilers.

    Directory of Open Access Journals (Sweden)

    Mengjie Guo

    Full Text Available P-glycoprotein (P-gp expression determines the absorption, distribution, metabolism and excretion of many drugs in the body. Also, up-regulation of P-gp acts as a defense mechanism against acute inflammation. This study examined expression levels of abcb1 mRNA and localization of P-gp protein in the liver, kidney, duodenum, jejunum and ileum in healthy and E. coli infected broilers by real time RT-PCR and immunohistochemistry. Meanwhile, pharmacokinetics of orally administered enrofloxacin was also investigated in healthy and infected broilers by HPLC. The results indicated that E. coli infection up-regulated expression of abcb1 mRNA levels significantly in the kidney, jejunum and ileum (P0.05. However, the expression level of CYP 3A37 mRNA were observed significantly decreased only in liver and kidney of E. coli infected broilers (P<0.05 compared with healthy birds. Furthermore, the infection reduced absorption of orally administered enrofloxacin, significantly decreased Cmax (0.34 vs 0.98 µg mL(-1, P = 0.000 and AUC0-12h (4.37 vs 8.88 µg mL(-1 h, P = 0.042 of enrofloxacin, but increased Tmax (8.32 vs 3.28 h, P = 0.040, T1/2a(2.66 vs 1.64 h(-1, P = 0.050 and V/F (26.7 vs 5.2 L, P = 0.040. Treatment with verapamil, an inhibitor of P-gp, significantly improved the absorption of enrofloxacin in both healthy and infected broilers. The results suggest that the E. coli infection induces intestine P-gp expression, altering the absorption of orally administered enrofloxacin in broilers.

  2. Distribution of flunixin meglumine and firocoxib into aqueous humor of horses.

    Science.gov (United States)

    Hilton, H G; Magdesian, K G; Groth, A D; Knych, H; Stanley, S D; Hollingsworth, S R

    2011-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. Fifteen healthy adult horses with no evidence of ophthalmic disease. Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E(2) in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated. Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE(2) concentrations showed no differences at any time point among study groups. Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  3. Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepT1

    DEFF Research Database (Denmark)

    Brodin, Birger; Nielsen, Carsten Uhd; Steffansen, Bente;

    2002-01-01

    peptide transport mechanism and enter the systemic circulation. As the number of new peptide and peptidomimetic drugs are rapidly increasing, the peptide transport system has gained increasing attention as a possible drug delivery system for small peptides and peptide-like compounds. In this paper we give...... capable of transporting a number of orally administered peptidomimetic drugs. Absorbed peptides may be hydrolysed in the cells due to the high peptidase activity present in the cytosol. Peptidomimetic drugs may, if resistant to the cellular enzyme activity, pass the basolateral membrane via a basolateral...

  4. Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

    Science.gov (United States)

    Cunha, Francisco Valmor Macedo; Gomes, Bruno de Sousa; Neto, Benedito de Sousa; Ferreira, Alana Rodrigues; de Sousa, Damião Pergentino; de Carvalho e Martins, Maria do Carmo; Oliveira, Francisco de Assis

    2016-01-01

    Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p activities (p activity in radiographic records (p activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.

  5. Cross-sectional age differences in personality among medicare patients aged 65 to 100.

    Science.gov (United States)

    Weiss, Alexander; Costa, Paul T; Karuza, Jurgis; Duberstein, Paul R; Friedman, Bruce; McCrae, Robert R

    2005-03-01

    1,084 older Medicare recipients were orally administered the NEO Five-Factor Inventory (NEO-FFI; P. T. Costa & R. R. McCrae, 1992). Participants were assigned to groups based on gender and age (65-79 or 80-100). An analysis of covariance showed that women had significantly higher Neuroticism, Openness, and Agreeableness scores; that older participants were significantly higher in Agreeableness; and that age differences in Agreeableness were significantly greater in men than in women. With the exception of Agreeableness, this study provides no evidence for age differences among those in the last decades of life.

  6. [Laryngitis in childhood].

    Science.gov (United States)

    Korppi, Matti; Tapiainen, Terhi

    2015-01-01

    The most common causative agents of laryngitis are parainfluenza viruses. The diagnosis of laryngitis in children is a clinical one, typical symptoms including dry, often barking cough and inspiratory difficulty and wheezing. Typical age of occurrence is 0.5 to 3 years. In children under one year of age the structural and functional anomalies causing symptoms resembling laryngitis in connection with an infection should not be disregarded. Most patients can be nursed at home. An orally administered glucocorticoid and inhaled racemic adrenalin are effective drugs in emergency service.

  7. [Anti-arrhythmia efficacy of propafenone per os in the prevention of paroxysmal supraventricular arrhythmia resistant to class Ia agents].

    Science.gov (United States)

    Boutaud, P; Guillem, J P; Maarek-Charbit, M; Amiel, A; Ciber, M; Herpin, D; Demange, J

    1989-01-01

    The efficacy of orally administered propafenone in the prevention of paroxysmal supraventricular dysrhythmias (atrial fibrillation, atrial tachysystole, reciprocal tachycardia) resistant to Vaughan-Williams class Ia drugs was investigated in 10 patients. Propafenone controlled dysrhythmia very well in 4 out of the ten patients, and satisfactorily in another one at a dosage ranging from 450 to 900 mg/day in 3 or 4 divided doses; this result was documented using continuous 24 hr. Holter ECG monitoring. Among the 5 clinical failures, 1 patient had atrial fibrillation primarily at night, and another poorly tolerated this agent which led to interrupt therapy.

  8. 未熟児無呼吸発作に対するCaffeine治療の発達薬理学的研究

    OpenAIRE

    若松, 章夫

    1988-01-01

    The efficacy of orally administered caffeine as a 1% (w/v) ethanolic solution (10%v/v) at a loading dose of 15mg/kg and a maintenance dose of 3mg/kg/24 hr was examined in 34 premature infants with idiopathic apnea. In 76% of the infants, a complete cessation of apneic spells was accomplished with a plasma caffeine concentration of 18.1±1.1 μg/ml (mean±S.E.) after the initial administration. Since the effective concentration of caffeine varied from infant to infant, the optimum concentration o...

  9. Shiva, Lord of Bhang.

    Science.gov (United States)

    Godlaski, Theodore M

    2012-08-01

    In India, Cannabis Indica has been used for literally thousands of years in the worship of the god Shiva. Cannabis is used in an orally administered form called bhang which can be either the wet resinous leaves formed into pills of a drink made of milk, cannabis, and various spices consumed by worshipers of Shiva on festival days or by smoking the flowering buds of cannabis-a practice generally reserved for holy men who dedicate their lives to ascetic practice and the worship of Shiva. This practice is codified in the Vedas as well as in legends about the origin of cannabis and its relationship to Shiva.

  10. Methylhonokiol attenuates neuroinflammation: a role for cannabinoid receptors?

    OpenAIRE

    Gertsch Jürg; Anavi-Goffer Sharon

    2012-01-01

    Abstract The cannabinoid type-2 G protein-coupled (CB2) receptor is an emerging therapeutic target for pain management and immune system modulation. In a mouse model of Alzheimer’s disease (AD) the orally administered natural product 4′-O-methylhonokiol (MH) has been shown to prevent amyloidogenesis and progression of AD by inhibiting neuroinflammation. In this commentary we discuss an intriguing link between the recently found CB2 receptor-mediated molecular mechanisms of MH and its anti-inf...

  11. Chiglitazar, a novel PPARalpha/gamma dual agonists with beneficial effects on insulin resistance and lipid metabolism in MSG rats

    Institute of Scientific and Technical Information of China (English)

    Ping-pingLI; Yue-tengCHEN; QuanLIU; Su-juanSUN; Zhu-fangSHEN

    2004-01-01

    AIM: Peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma agonists lower lipid accumulation by different mechanisms. We investigated whether benefits could be achieved on insulin sensitivity and lipid metabolism by the dual PPARalpha/gamma agonist chiglitazar in MSG rats. METHODS: Chiglitazar was orally administered in 5, 10, 20 mg-kg-~.d~ dosages in MSG rats for 40 d. The drug therapeutic effect was evaluated by glucose tolerance tests, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps technique. The level of

  12. Role of oxidative stress in ethanol induced germ cell apoptosis — An experimental study in rats

    OpenAIRE

    Maneesh, M.; Jayalekshmi, H; Dutta, Sanjiba; Chakrabarti, Amit; Vasudevan, D. M.

    2005-01-01

    The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was p...

  13. In vitro characterisation of PLGA nanoparticles encapsulating rifampicin and isoniazid - Towards IVIVC

    CSIR Research Space (South Africa)

    Booysen, L

    2010-09-01

    Full Text Available , 561-573 (2006). 5. s. stolnik et al. The effect of surface coverage and conformation of poly(ethylene oxide) (PEO) chains of poloxamer 407 on the biological fate of model colloidal drug carriers, 1514 BIocHIMIcA Et BIoPHYsIcA ActA (BBA) - BIo... nanoparticles of 1% PEG or 1% Pluronics-F127, these formulations were fluorescently labelled with rhodamine 6G and orally administered to mice at 4 mg particles in 0.2 ml sterile saline by oral gavage. the biodistribution of uncoated PLGA nanoparticles...

  14. Effect of some anesthetics on memory and exploration.

    Science.gov (United States)

    Valzelli, L; Kozak, W; Skorupska, M

    1988-04-01

    A light ether anesthesia in laboratory mice resulted in the complete drop of their memory retrieval to zero for more than three days after the administration. On the contrary, mice that underwent the exploration test after the light ether anesthesia performed as expected, confirming that impairment of memory does not necessarily reflect on exploratory performance. The effect of some anesthetic drugs was then studied on memory retrieval and exploratory behavior. Within this general framework, the anesthetics here studied all worsen memory retrieval, however without inducing clear and long-lasting amnesic effect comparable to that exerted by ether anesthesia. Contrarily, the classically amnesic drug scopolamine, orally administered, enhances memory retrieval and improves exploration.

  15. Two Oral Midazolam Preparations in Pediatric Dental Patients: A Prospective Randomised Clinical Trial

    OpenAIRE

    Katayoun Salem; Shaqayegh Kamranzadeh; Maryam Kousha; Shahnaz Shaeghi; Fatemeh AbdollahGorgi

    2015-01-01

    Pharmacological sedation is an alternative behavior management strategy in pediatric dentistry. The aim of this study was to compare the behavioral and physiologic effects of “commercially midazolam syrup” versus “orally administered IV midazolam dosage form (extemporaneous midazolam (EF))” in uncooperative pediatric dental patients. Eighty-eight children between 4 to 7 years of age received 0.2–0.5 mg/kg midazolam in this parallel trial. Physiologic parameters were recorded at baseline and e...

  16. Iron-deficiency anemia caused by a proton pump inhibitor.

    Science.gov (United States)

    Hashimoto, Rintaro; Matsuda, Tomoki; Chonan, Akimichi

    2014-01-01

    A 59-year-old man was orally administered rabeprazole, a proton pump inhibitor (PPI), for gastroesophageal reflux disease, after which he gradually developed iron-deficiency anemia. The anemia did not improve following the administration of ferrous fumarate, and endoscopic screening of the entire gastrointestinal tract, including the small intestine, did not reveal any findings indicating the cause of the anemia. The patient was then switched from rabeprazole to famotidine and the anemia was cured within three months. There is much debate as to whether the long-term use of PPIs causes iron-deficiency. However, this case strongly suggests that PPIs can induce iron-deficiency anemia.

  17. Oral antibiotics for perforated appendicitis is not recommended

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg, Jacob; Alamili, Mahdi

    2010-01-01

    In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this paper...... was to give an overview of studies on acute perforated appendicitis with postoperative oral antibiotics. Five studies were found in a database search covering the 1966-2009 period. There is no evidence to support a conversion of the postoperative antibiotic regimen from intravenous to oral administration...

  18. EFFECT OF IMIDACLOPRID ON THE BIOCHEMICAL CONTENTS OF KIDNEYS IN MALE SWISS ALBINO MICE

    Directory of Open Access Journals (Sweden)

    M. NAGA PRASANNA

    2013-01-01

    Full Text Available Six groups (A, B, C, D, E and F of male Swiss albino mice (Mus musculus albinus were orally administered withvaried doses (0.4, 0.8, 1.6, 3.2, 4.0 and 8.0 mg/kg bw/mouse of imidacloprid; they showed significant decreasein protein, DNA and RNA content in the kidneys of all the treated groups of mice throughout the experimentalperiod (on day 1, 4, 8, 12, 16 and 30 of treatment when compared with controls. It is clear from the results thatthe insecticide caused marked disturbance in the metabolism of protein, DNA and RNA.

  19. ASSESSMENT OF IVERMECTIN THERAPEUTIC EFFICACY ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN MICE EXPERIMENTALLY INFECTED

    OpenAIRE

    BARBOSA, Carlos Augusto Lopes; Campos,Dulcinéa Maria Barbosa; Oliveira,Jayrson Araújo de

    1998-01-01

    In this study we evaluated the potential action of ivermectin on third-stage larvae, both at migratory and encysted phases, in mouse tissues after experimental infection with Lagochilascaris minor. Study groups I and II consisted of 120 mice that were orally administered 1,000 parasite eggs. In order to assess ivermectin action upon migratory larvae, group I (60 mice) was equally split in three subgroups, namely I-A, I-B, and I-C. On the 7th day after inoculation (DAI), each animal from the s...

  20. Oral cadmium chloride intoxication in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B; Svendsen, P

    1988-01-01

    Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect....... Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered...

  1. Assessment of hypoglycemic activity of the aqueous extract of Abuta grandifolia (Mart.) in diabetic rats induced by alloxan

    OpenAIRE

    Justil, Carlos; Laboratorio de Farmacología, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima; Angulo H., Pedro; Laboratorio de Farmacología, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima; Justil G., Hugo; Laboratorio de Farmacología, Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima; Arroyo A., Jorge; Laboratorio de Farmacología, Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima

    2015-01-01

    Abuta grandifolia is a native plant from the Amazon region, traditionally used in the control of diabetes mellitus. The aim of the present study was to evaluate the effectiveness of reducing the glucose level when the aqueous extract (AE) ofA. grandifolia (Mart.) is orally administered in diabetic rats induced by alloxan. Thirty Sprague Dawley male rats, 3-month-old, body weight of 240 ± 10 g were used. The animals were distributed in six groups (negative control, positive control, treated wi...

  2. Oral Alitretinoin for the Treatment of Recalcitrant Pityriasis Rubra Pilaris

    Directory of Open Access Journals (Sweden)

    Laurenz Schmitt

    2011-04-01

    Full Text Available Treatment of pityriasis rubra pilaris is still challenging. We here present a 74-year-old woman who had not experienced stable remission of her skin symptoms during prior treatments including topical and systemic corticosteroids, phototherapy, orally administered acitretin, cyclosporine, methotrexate and adalimumab. A therapy with oral alitretinoin was started and tolerated very well. After a few weeks, skin condition improved significantly and itching and scaling disappeared. The present case shows that alitretinoin might be an alternative in the treatment of recalcitrant pityriasis rubra pilaris type I. Further studies are needed to investigate the benefit of this encouraging result.

  3. Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports.

    Science.gov (United States)

    Brickell, K; Porter, D; Thompson, P

    2003-08-18

    Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil).

  4. Amphotericin B cochleates: a vehicle for oral delivery.

    Science.gov (United States)

    Perlin, David S

    2004-02-01

    Cochleates are a novel lipid-based delivery vehicle consisting of crystalline phospholipid-cation structures that form spiral lipid sheets. They represent a new technology platform for oral delivery of clinically important drugs that possess poor oral bioavailability. Orally administered cochleates containing amphotericin B (CAMB) showed broad-spectrum activity in murine infection models of candidiasis, aspergillosis and cryptococcosis. Initial biodistribution studies of CAMB administered orally in mice demonstrated that cochleates delivered significant levels of AMB to target organs. The lipid particulate nature of cochleates also imparted reduced toxicity that mimics other lipid-amphotericin B complexes. Cochleates are a promising new vehicle for oral delivery of amphotericin B at therapeutic levels.

  5. Aflatoxin effect on the oocysts morphometry and contribution on the morphology of Eimeria bateri Bhatia, Pandey and Pande, 1965 from the japanese quail Coturnix japonica in Brazil Efeito da aflatoxina sobre a morfometria dos oocistos e contribuição para a morfologia de Eimeria bateri Bhatia, Pandey and Pande, 1965 da Codorna japonesa Coturnix japonica no Brasil

    OpenAIRE

    Bruno P. Berto; Sergian V. Cardozo; Walter L. Teixeira Filho; Ana Maria R. Ferreira; Lopes,Carlos Wilson G.

    2008-01-01

    The purpose of this study was to characterize Eimeria bateri oocysts and to evaluate the aflatoxin effect in the morphometry of sporulated oocysts in Japanese quails infected naturally. Of a total of 50 quails naturally infected by E. bateri were randomly divided into two groups with 25 birds each. In one of them, quails were orally administered with aflatoxin in dose of 0.04 mg/kg body weight previously. Both experimental groups shed E. bateri oocysts. These oocysts were subspherical to elli...

  6. sup 99m Tc-sucralfate scintigraphy in inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Mortensen, P.B.; Lech, Y.; Moeller-Petersen, J.; Vilien, M.; Fallingborg, J. (Aalborg Sygehus (Denmark)); Ekelund, S. (Copenhagen County Hospital (Denmark))

    1989-01-01

    Technetium-99m-labelled albumin-sucralfate was orally administered to 11 patients (Crohn's disease, 8; ulcerative colitis, 3) and 3 healthy volunteers. Serial scintigraphy was performed, and scintigraphic interpretations were compared with radiographic end endoscopic findings in an open study. It was not possible in any patient to relate the scintigraphic findings to the localizations of inflammatory bowel disease, nor was it possible to distinguish the scans in the patients from the scans of the healthy volunteers. It is concluded the {sup 99m}Tc-albumin-sucralfate scintigraphy is of no value in the detection of inflammatory bowel disease. 8 refs.

  7. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    Science.gov (United States)

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  8. The effect of Zymomonas mobilis culture on experimental Schistosoma mansoni infection O efeito da cultura de Zymomonas mobilis na infecção experimental por Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Juliana de Fátima Macedo Santos

    2004-12-01

    Full Text Available C57Bl/10 male mice infected with Schistosoma mansoni were distributed into mixed, prophylactic and curative groups. A culture of Zymomonas mobilis was orally administered to mice. A 61% protection from the infection was observed in the curative group (p Camundongos C57Bl/10 do sexo masculino, infectados com Schistosoma mansoni foram distribuídos nos grupos misto, profilático e curativo. Cultura de Zymomonas mobilis foi administrada oralmente aos camundongos. Uma proteção de 61% foi observada no grupo curativo (p<0,05. Os estudos histopatológicos dos fígados e intestinos mostraram resultados similares.

  9. Tremorgenic Toxin from Penicillium verruculosum

    Science.gov (United States)

    Cole, R. J.; Kirksey, J. W.; Moore, J. H.; Blankenship, B. R.; Diener, U. L.; Davis, N. D.

    1972-01-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD50) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD50 values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name „verruculogen” is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described. PMID:4341967

  10. Tremorgenic toxin from Penicillium veruculosum.

    Science.gov (United States)

    Cole, R J; Kirksey, J W; Moore, J H; Blankenship, B R; Diener, U L; Davis, N D

    1972-08-01

    A new mycotoxin that produces severe tremors and acute toxicity when administered orally or intraperitoneally (ip) to mice and 1-day-old cockerels was obtained from a strain of Penicillium verruculosum Peyronel isolated from peanuts. The ip 50% lethal dose (LD(50)) of this tremorgen was 2.4 mg/kg in mice and 15.2 mg/kg in chickens. Orally administered LD(50) values for the toxin were 126.7 mg/kg in mice and 365.5 mg/kg in chickens. The trivial name "verruculogen" is proposed for this tremorgenic mycotoxin. Physical and chemical characteristics of the mycotoxin are described.

  11. Teratogenicity Test of Pyraoxystrobin TC on Rat%唑菌酯原药大鼠致畸毒性试验

    Institute of Scientific and Technical Information of China (English)

    韦春晟; 廖雪; 鲍清

    2016-01-01

    [Aims] The potential embryonal toxicity and teratogenic effects ofpyraoxystrobin TC on Sprague Dawley rat were determined.[Methods] The three groups of rats were orally administered and gavage with pyraoxystrobin at 5,15 and 45 mg/kg b.w.continuously for 14 days from 6 th to 19 th day after gestation.In addition,the rats of negative control were orally administered with sodium carboxymethyl cellulose solution at 0.5%(w/v) were performed as the same time.[Results] Compared to the rats of negative conmol,when the rats were orally administered with pyraoxystrobin at 15 and 45 mg/kg b.w.,the the weight gain of the pregnant rats was signifycantly lower.In addition,weight gain of the fetus was signifycantlylower (P<0.001).[Conclusions] When the rats were orally administered with pyraoxystrobin at 15 mg/kgb.w,the weight gain of the pregnant rats was affected.When the dose was 5 mg/kg,the growth rate of the fetus was affected,however,there was no teratogenic effect on rats.%[目的]测定唑菌酯原药对大鼠致畸方面的影响.[方法]应用Sprague Dawley(SD)大鼠为试验动物,设计5、15、45 mg/kg b.w.3个剂量组和1个阴性对照组来测定唑菌酯原药对动物致畸的影响.[结果]大鼠经口灌胃给予唑菌酯原药15、45 mg/kg b.w.两个剂量组动物和对照组动物相比,出现显著性的体质量增长缓慢;各剂量组胎鼠体质量也出现增长缓慢.[结论]经口灌胃给药15 mg/kg b.w.时,对孕鼠体质量增长有影响;给药5mg/kg时,对胎仔的生长速度有影响;但并无致畸作用.

  12. Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata)

    OpenAIRE

    Thakur, Ajit Kumar; Chatterjee, Shyam Sunder; Kumar, Vikas

    2014-01-01

    Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (穿心蓮 chuān xīn lián), a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive ...

  13. Magnolol Protects against MPTP/MPP+-Induced Toxicity via Inhibition of Oxidative Stress in In Vivo and In Vitro Models of Parkinson’s Disease

    OpenAIRE

    Akiko Muroyama; Aya Fujita; Cheng Lv; Shota Kobayashi; Yoshiyasu Fukuyama; Yasuhide Mitsumoto

    2012-01-01

    The aim of this study is to investigate the role of magnolol in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-) induced neurodegeneration in mice and 1-methyl-4-phenylpyridinium ion-(MPP+-) induced cytotoxicity to human neuroblastoma SH-SY5Y cells and to examine the possible mechanisms. Magnolol (30 mg/kg) was orally administered to C57BL/6N mice once a day for 4 or 5 days either before or after MPTP treatment. Western blot analysis revealed that MPTP injections substantially ...

  14. Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR pigs challenged with an F4+ ETEC/VTEC/EPEC strain

    DEFF Research Database (Denmark)

    Zhou, Dong; Zhang, Wei; Wang, Meng-Ling

    2015-01-01

    Although breeding of F4 receptor − negative (F4R−) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR− pigs for 1 week before F4 (K88) − ...... of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases....

  15. Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Diego Carlos dos Reis

    2014-02-01

    Full Text Available The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

  16. The Effect of Carnitine Supplementation on Hyperammonemia and Carnitine Deficiency Treated with Valproic Acid in a Psychiatric Setting

    OpenAIRE

    Nakamura, Masaru; Nagamine, Takahiko

    2015-01-01

    Objective: The aim of this study was to investigate the effect of levocarnitine (active isoform of carnitine, L-Carnitine) supplementation on serum ammonia and carnitine levels simultaneously, and their clinical outcomes in valproic acid-treated psychiatric subjects.

  17. Hypokalemic paralysis and respiratory failure due to excessive intake of licorice syrup

    Directory of Open Access Journals (Sweden)

    Mehmet Oguzhan Ay

    2014-04-01

    Full Text Available Licorice is the root of Glycyrrhiza glabra, which has a herbal ingredient, glycyrrhizic acid. Excessive intake of licorice may cause a hypermineralocorticoidism-like syndrome characterized by sodium and water retention, hypokalemia, hypertension, metabolic alkalosis, low-renin activity, and hypoaldosteronism. In this paper, an 34 years old man who admitted to the emergency department with respiratory failure and marked muscle weakness of all extremities that progressed to paralysis after excessive intake of licorice syrup was presented. It was aimed to draw attention to the necessity of questioning whether there is excessive intake of licorice or not in patients who admitted to emergency department with paralysis and dyspnea. Plasma potassium concentration of the patient was 1.4 mmol/L. The patient\\'s respiratory distress and loss of muscle strength recovered completely after potassium replacement. [Cukurova Med J 2014; 39(2.000: 387-391

  18. Antioxidative activity and stability of the extracts of liquorice root (Glycyrrhiza glabra

    Directory of Open Access Journals (Sweden)

    Simona PATRICHE

    2015-12-01

    Full Text Available The active principles from the aqueous liquorice plant extracts were investigated and quantified by evaluation of bioactive compounds (saponins through phytochemical reactions. The presence of saponins was evaluated by measuring the foam index, which was around 500. A major component was Glycyrrhizic acid, responsible for the antioxidant activity, found in concentration of 5.82 % at plant maturity. A time-dependent decrease in concentration of the bioactive compounds from aqueous liquorice extracts was observed. The antimicrobial activity of the extracts was tested by the agar diffusion method, showing a moderate inhibitory activity against Bacillus sp. and strong inhibitory activity against coliforms. A liquorice syrup was obtained and subsequently could be used as nutraceutical additive in bread with good results, showing characteristic, optical and antimicrobial properties and good stability in time. Adding liquorice syrup in food products could be an alternative to improve nutraceutical potential.

  19. 微波干燥在乌梅人丹生产中的应用研究%Study on the application of microwave-drying in the production of Wumei Rendan

    Institute of Scientific and Technical Information of China (English)

    杜子荣; 张正滢; 邹敏

    2014-01-01

    目的:比较乌梅人丹用烘箱干燥和微波干燥的效果。方法:以溶散时限、水分、薄荷脑含量、甘草酸含量为指标,比较其效果。结果与结论:微波干燥可提高产品质量、提高生产能力、降低能耗,优于烘箱干燥。。%Objective: To compare the effects of two different methods (oven drying vs microwave drying ) on the dryness of Wumei Rendan. Methods:Their efifcacy was compared by taking the time limit of dissolution, moisture, and the contents of menthol and glycyrrhizic acid as indicators. Results&Conclusion:Microwave-drying can improve product quality, increase production capacity and reduce energy consumption and is superior to oven drying.

  20. Exogenously-induced apparent hypermineralocorticoidism associated with ingestion of "asam boi".

    Science.gov (United States)

    Hamidon, B B; Jeyabalan, V

    2006-02-01

    A 31-year-old woman presented with a one-week history of headache, generalised lethargy, weakness and poor appetite. Clinical examination showed that her blood pressure was 200/120 mmHg. On an earlier occasion, her blood pressure was found to be normal by a general practitioner whom she last visited three months earlier when she had an upper respiratory tract infection. Investigations showed hypokalaemia, suppressed serum renin and aldosterone. Further history was taken and revealed that she had been craving for guava fruits which she ate with flavoured "asam boi" (containing glycyrrhizic acid) at least three spoonfuls twice a day for the past six weeks. The hypertension and hypokalaemia resolved after two weeks of stopping the "asam boi". Her clinical picture was compatible with exogenously-induced hypermineralocortoidism.

  1. [Identification of the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration].

    Science.gov (United States)

    Lu, Lin-ling; Shu, Yan; Qian, Da-wei; Su, Shu-lan; Duan, Jin-ao; Qian, Ye-fei; Xue, Cai-fu

    2011-11-01

    Sinisan is a widely used traditional Chinese medicine (TCM) in treating various diseases; however, the in vivo metabolic profile of its multiple components remains unknown. In this paper, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration. Using MS(E) and mass defect filter techniques, 41 metabolites of 10 parent compounds (naringin, naringenin, hesperidin, neohesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, saikosaponin a and saikosaponin d) were detected and tentatively identified. It was shown by our results that these compounds was metabolized to the forms of hydroxylation, glucuronidation, sulfation, glucuronidation with sulfation and glucuronidation with hydroxylation in vivo.

  2. Ultrasound-assisted extraction methodology as a tool to improve the antioxidant properties of herbal drug Xiao-chia-hu-tang.

    Science.gov (United States)

    Liu, Chu-Ting; Wu, Ching-Yi; Weng, Yih-Ming; Tseng, Chin-Yin

    2005-06-03

    Xiao-chai-hu-tang (XCHT) is an important Chinese herbal prescription for curing many types of liver diseases. The contents of bioactive constituents (saikosaponins a, c and d, baicalin, baicalein, and glycyrrhizic acid), and antioxidant properties of XCHT extracts prepared with ultrasound-assisted (US) extraction in combination with ethanol (up to 95%) as extraction modifier were studied. The results showed that the US extraction significantly increased the bioactive constituents concentrations and antioxidant properties of XCHT extracts when compared with the XCHT prepared with traditional boiling-water extraction. Among the XCHT extracts made with US extraction, the sample prepared with 95% ethanol showed the highest bioactive constituent concentrations and the best antioxidant functionalities. The results suggest that US extraction of XCHT is feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable Chinese herbal medicine.

  3. Study of New Technology of the Preparation of Glycrrhizic Acid from Licorice%甘草酸制备新工艺的研究

    Institute of Scientific and Technical Information of China (English)

    崔杏雨; 崔健; 陈树伟

    2001-01-01

    用连续提取装置一次性完成甘草酸提取过程,以AB-8大孔吸附树脂法分离甘草酸,最后用活性炭纯化。甘草酸收率较一般方法高,达70%~80%,纯度90%以上,操作简便。%Glycyrrhizic acid from licorice was entracted with continuous extraction device and was separated with macroporous absorbent AB-8. The crude product was purified with active charcoal to get a colorless or pale yellow product. The total yields range from 70% to 80% and purities are up to 90%. This facile method gives a higher yield than conventional ones.

  4. 盐酸伐昔洛韦与复方甘草酸苷片联合治疗初发性生殖器疱疹临床观察%Clinical Treatment Observation of Valaciclovir Hydrochloride Combined With Compound Glycyrrhizin Tablets in Primary Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    王艳

    2016-01-01

    Objective Hydrochloride on cutting famciclovir combined with compound glycyrrhizic acid glucoside tablets in the treatment of early send sexual genital bleb clinical effect.Methods 86 cases of primary genital herpes patients were divided into study group (HCl valaciclovir+ compound licorice tablets) and control group (valaciclovir).ResultsThe total effective rate of the study group was higher than that of the control group (P0.05).Conclusion Hydrochloric acid cutting famciclovir combined with compound glycyrrhizic acid glucoside tablets in the treatment of early send sexual genital bleb has a good clinical effect.%目的:探讨盐酸伐昔洛韦联合复方甘草酸苷片治疗初发性生殖器疱疹的临床效果。方法将86例初发性生殖器疱疹患者分为研究组(盐酸伐昔洛韦+复方甘草酸苷片)和对照组(盐酸伐昔洛韦)。结果研究组总有效率高于对照组(P<0.05);复发率低于对照组(P<0.05);两组不良反应发生率无统计学差异(P>0.05)。结论盐酸伐昔洛韦联合复方甘草酸苷片治疗初发性生殖器疱疹有较好临床效果。

  5. Comparison of quality and yield of different genotype Glycyrrhiza uralensis%不同基因型甘草品质及产量的比较

    Institute of Scientific and Technical Information of China (English)

    柴娜; 张颖; 王景安

    2011-01-01

    A culture experiment was conducted to compare the quality and yield of different genotype Glycyrrhiza uralensis for selecting the fine licorice lines of G. uralensis by measuring the biomass, glycyrrhizic acid contents, flavoniods, polysaccharide, soluble sugars, amino acid and protein. This study showed that the yield and the glycyrrhizic acid content of the strains with good quality and high yield were 3 and 1.6 times that of the strains with poor quality and low yield, respectively. The comprehensive analysis showed that the plant height was not correlative relationship with the quality and stem color, while the yields of high-green plants were higher than that of low-purple ones.%以甘草(Glycyrrhiza uralensis)为试验材料,用营养液培养的方法,研究了不同基因型甘草生物量、甘草酸等药用成分及可溶性糖、氨基酸、蛋白质等含量的差异,为筛选优良甘草株系提供材料和科学依据。试验结果显示,选出的品质好、产量高的株系,其甘草酸含量是含量最低者的1.6倍,产量是最低产量株系的近3倍。综合分析认为,高大绿茎植株的产量高于矮小紫茎植株,但甘草品质的优劣与植株高矮及茎秆颜色没有必然联系。

  6. The Adsorptions of Three Licorice Derivatives by Multi-walled Carbon Nanotubes%多壁碳纳米管对甘草中3种有效成分的选择性吸附

    Institute of Scientific and Technical Information of China (English)

    赵洁; 李超鹏; 韩博; 陈文

    2011-01-01

    The adsorptions of three licorice derivatives including, isoliquiritin, liquiritin and glycyrrhizic acid on multi-walled carbon nanotubes(MWNTs), were investigated using UV and HPLC techniques. The effects of adsorption time, initial concentration, solution volume and its pH value on the adsorption of ciprofloxacin are examined. MWNTs have totally different adsorptive capacities toward the three main components. In the multi-component competitive adsorption examination, a noncompetitive adsorption process was observed. The adsorption capacity of MWNTs for isoliquiritin is higher than those for liquiritin and glycyrrhizic acid. MWNTs may be potentially applied to the separation and purification of isoliquiritins.%考察了多壁碳纳米管(MWNTs)对3种甘草有效成分异甘草苷、甘草苷和甘草酸的吸附性能.分别用紫外分光光度法和HPLC法测定了吸附前后溶液中异甘草苷、甘草苷、甘草酸的含量,考察了静态吸附实验时间、料液起始浓度、溶液体积和pH值对各成分吸附的影响.结果显示,MWNTs对甘草中3种主要有效成分的吸附量明显不同,对异甘草苷的吸附远大于甘草苷和甘草酸,并且不存在竞争吸附,具有明显的选择性吸附特点.

  7. The Pathogenesis of Alcohol-Induced Airflow Limitation in Acetaldehyde Dehydrogenase 2-Deficient Mice.

    Science.gov (United States)

    Shimoda, Terufumi; Obase, Yasushi; Matsuse, Hiroto; Asai, Sadahiro; Iwanaga, Tomoaki

    2016-01-01

    In Japanese patients, alcohol-induced asthma is attributed to elevated plasma concentrations of acetaldehyde following alcohol consumption because of an acetaldehyde dehydrogenase 2 gene (ALDH2) polymorphism. The resulting increase in plasma histamine concentrations seems to trigger the onset of asthma symptoms. However, the specific pathogenic mechanism underlying this response remains unclear. ALDH2-deficient mice were therefore generated to investigate the pathogenesis of alcohol-induced asthma. ALDH2-deficient mice were generated using embryonic stem cells that were derived from C57BL/6 mice. The resulting mice were backcrossed into the BALB/c mice background. Exon 1 of ALDH2 was replaced with the Neo cassette. Pure ethanol was orally administered to ALDH2-deficient and wild-type mice, and the plasma concentrations of ethanol, acetaldehyde, and histamine, in addition to enhanced pause (Penh) values, were determined and compared between the 2 groups. We established an ALDH2-deficient mouse line to compare responses between wild-type and ALDH2-deficient mice receiving orally administered ethanol. The results showed that the plasma concentrations of acetaldehyde (p alcohol-induced asthma using ALDH2-deficient mice. The results demonstrated that alcohol intake resulted in an increase in acetaldehyde levels, and a subsequent increase in histamine levels, which induced airway constriction. Alcohol consumption is known to be an important factor that exacerbates bronchial asthma, and studies investigating this factor are useful for the treatment of patients with alcohol-induced asthma. © 2017 S. Karger AG, Basel.

  8. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara

    2014-01-01

    BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the tre......BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib...... in the treatment of patients with this type of cancer. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice daily) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid...... in the sorafenib group were hand-foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash or desquamation (50·2%). INTERPRETATION: Sorafenib significantly improved progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory differentiated thyroid...

  9. Oral distension methods for small bowel MRI: comparison of different agents to optimize bowel distension.

    Science.gov (United States)

    Schmidt, Stefan A; Baumann, Julia A; Stanescu-Siegmund, Nora; Froehlich, Eckhart; Brambs, Hans-Juergen; Juchems, Markus S

    2016-12-01

    Background Different methods for bowel distension prior to magnetic resonance imaging (MRI) examinations were described in recent years. Purpose To compare orally administered psyllium or locust bean gum / mannitol (LBM) with tylose administered through a duodenal catheter for bowel distension in patients undergoing MRI examination of the small bowel. Material and Methods Three different methods of bowel distension prior to MRI were compared: tylose applied through a duodenal catheter and orally administered psyllium and LBM in three groups with 15 patients each. Datasets were blinded and reviewed independently by two experienced radiologists, who assessed the diagnostic value and the maximum luminal diameter. Results Tylose was superior to psyllium and LBM in the examination of the duodenum and proximal jejunum. LBM was superior to the other methods for distension of the ileum and terminal ileum. The greatest luminal diameter of the duodenum was achieved after tylose and distension of the terminal ileum was the best in patients receiving LBM. The psyllium group was inferior to the other two groups in all segments. Conclusion By using LBM as an oral method of bowel distension, many patients can avoid the unpleasant placement of a duodenal catheter without compromising the diagnostic value of the examination.

  10. Effects of menthol on the pharmacokinetics of triazolam and phenytoin.

    Science.gov (United States)

    Hoshino, Motohiro; Ikarashi, Nobutomo; Hirobe, Ryuta; Hayashi, Mami; Hiraoka, Hironori; Yokobori, Kohsuke; Ochiai, Takumi; Kusunoki, Yoshiki; Kon, Risako; Tajima, Masataka; Ochiai, Wataru; Sugiyama, Kiyoshi

    2015-01-01

    We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration-time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.

  11. A Minireview: Usefulness of Transporter-Targeted Prodrugs in Enhancing Membrane Permeability.

    Science.gov (United States)

    Murakami, Teruo

    2016-09-01

    Orally administered drugs are categorized into 4 classes depending on the solubility and permeability in a Biopharmaceutics Classification System. Prodrug derivatization is one of feasible approaches in modifying the physicochemical properties such as low solubility and low permeability without changing the in vivo pharmacological action of the parent drug. In this article, prodrug-targeted solute carrier (SLC) transporters were searched randomly by PubMed. Collected SLC transporters are amino acid transporter 1, bile acid transporter, carnitine transporter 2, glucose transporter 1, peptide transporter 1, vitamin C transporter 1, and multivitamin transporter. The usefulness of transporter-targeted prodrugs was evaluated in terms of membrane permeability, stability under acidic condition, and conversion to the parent drug. Among prodrugs collected, peptide transporter-targeted prodrugs exhibited the highest number, and some prodrugs such as valaciclovir and valganciclovir are clinically available. ATP-binding cassette efflux transporter, P-glycoprotein (P-gp), reduces the intestinal absorption of lipophilic P-gp substrate drugs, and SLC transporter-targeted prodrugs of P-gp substrate drugs circumvented the P-gp-mediated efflux transport. Thus, SLC transporter-targeted prodrug derivatization seems to be feasible approach to increase the oral bioavailability by overcoming various unwanted physicochemical properties of orally administered drugs, although the effect of food on prodrug absorption should be taken into consideration.

  12. Difficulties in administration of oral medication formulations to pet cats: an e-survey of cat owners.

    Science.gov (United States)

    Sivén, M; Savolainen, S; Räntilä, S; Männikkö, S; Vainionpää, M; Airaksinen, S; Raekallio, M; Vainio, O; Juppo, A M

    2017-03-11

    The purpose here was to determine the problems cat owners encounter in medicating their cats with orally administered drugs at home. The study was carried out as an open e-questionnaire survey addressed to cat owners in which the authors focused on the oral administration route. A total of 46 completed questionnaires were included in the survey. In the study, 46 cats received 67 orally administered drugs. Approximately half of the drugs were registered for use in cats by the European Medicines Agency (54 per cent), and there were also off-label drugs registered for human (36 per cent) and canine medication (7.4 per cent) and an ex tempore drug (3.0 per cent). The owners were unable to give the doses as prescribed for their cats for one-fourth of the medications (16/67). Drugs that were registered for feline medication were significantly more palatable than drugs registered for other species (odds ratio (OR) 4.9), and liquid formulations were significantly more palatable than solid formulations (OR 4.8). However, most of the owners (22/38) preferred a solid dosage form, while few (4/38) chose a liquid formulation. The results indicate that there is still a need for more palatable and easily administered oral drugs for cats.

  13. Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract

    Directory of Open Access Journals (Sweden)

    Chihiro Tohda

    2006-01-01

    Full Text Available We aimed to compare the anti-inflammatory activities of six species of Curcuma drugs using adjuvant arthritis model mice. When orally administered 1 day before the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling and the serum haptoglobin concentration in adjuvant arthritis mice. Also when orally administered 1 day after the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling. Other Curcuma species (Curcuma longa, Curcuma wenyujin, Curcuma kwangsiensis, Curcuma zedoaria and Curcuma aromatica had no significant inhibitory effects on adjuvant-induced paw swelling. Cyclooxygenase (COX-2 activity was significantly inhibited by the methanol extract of C. phaeocaulis. Curcuminoids' (curcumin, bis-demethoxycurcumin and demethoxycurcumin were rich in C. longa, but less in C. phaeocaulis and C. aromatica, not in C. wenyujin, C. kwangsiensis and C. zedoaria, suggesting that curcuminoids' contents do not relate to inhibition of arthritis swelling. Therefore, C. phaeocaulis may be a useful drug among Curcuma species for acute inflammation, and the active constituents of C. phaeocaulis are not curcuminoids.

  14. Quercetin prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced testicular damage in rats.

    Science.gov (United States)

    Ciftci, O; Aydin, M; Ozdemir, I; Vardi, N

    2012-06-01

    The protective effect of quercetin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular damage in rats was investigated. Twenty-two rats were equally divided into four groups; first group was kept as control and given corn oil as carrier. In second group, TCDD was orally administered at the dose of 2 μ (kg week)(-1) for 60 days. In third group, quercetin was orally administered at the dose of 20 mg (kg day)(-1) by gavages, and in fourth group TCDD and quercetin were given together at the same doses. Although TCDD increased the formation of thiobarbituric acid reactive substances (TBARS) significantly, it caused a significant decline in the levels of glutathione (GSH), catalase (CAT), GSH-Px and CuZn-Superoxide Dismutase (CuZn-SOD) in rats. In contrast, quercetin significantly increased the GSH, CAT, GSH-Px and CuZn-SOD levels but decreased the formation of TBARS. In addition, sperm motility, sperm concentration and serum testosterone levels were significantly decreased but abnormal sperm rate and testicular damage were increased with TCDD treatment. However, these effects of TCDD on sperm parameters, histological changes and hormone levels were eliminated by quercetin treatment. Our results show that administration of TCDD induces testicular damage (oxidative stress, testes tissue damage, serum hormone level and sperm parameters), and quercetin prevents TCDD-induced testicular damage in rats. Thus, quercetin may be useful for the prevention and treatment of TCDD-induced testicular damage.

  15. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity.

    Science.gov (United States)

    Liu, Shuangyue; Zhang, Xiao; Sun, Meiling; Xu, Tao; Wang, Aimei

    2017-07-01

    The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.

  16. Dietary Hyaluronic Acid Migrates into the Skin of Rats

    Directory of Open Access Journals (Sweden)

    Mariko Oe

    2014-01-01

    Full Text Available Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid. 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine.

  17. Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

    Science.gov (United States)

    Wakabayashi, Ayako; Kumagai, Yoshihiro; Watari, Eiji; Shimizu, Masumi; Utsuyama, Masanori; Hirokawa, Katsuiku; Takahashi, Hidemi

    2006-01-01

    Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction. PMID:16796692

  18. Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

    Science.gov (United States)

    Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi

    2014-11-01

    Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides.

  19. Literary investigation on the origin of poppy and other narcotics Research Articles

    Directory of Open Access Journals (Sweden)

    Lim Chung San

    2009-06-01

    Full Text Available Objectives : This study was performed to developing orally administered analgesics and locally injected pharmacopuncture analgesics like opioids. Methods : Literary investigation on the origin of poppy (Papaver somniferum L and other narcotics was conducted to examine the potential of developing orally administered analgesics and locally injected pharmacopuncture analgesics. Opium is a gum-like mass derived from air-dried white fluid of immature fruit of the poppy. Opium contains approximately 20 types of alkaloids including morphine, codeine, thebaine, papaverine and others. Natural opioids and synthetic alkaloid derivatives are the constituents of opioid analgesics and their effects and side-effects depend on the peculiarities of receptors. An extreme caution is required in the selection of proper dosage, proper analgesic types, and indications for successful pain management. Results and Discussion : With the enactment of "Narcotic control protocol", herbs such as cannibis and poppy are no longer available for use by Korean medicine doctors, and these doctors are faced with difficulty in managing severe pain in the clinical environment. A systematic consideration is inevitable for overcoming the limitation on these analgesics.

  20. The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Kazushiro Takata

    Full Text Available BACKGROUND: Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and autoimmune diseases; one of which is Multiple sclerosis (MS which affects the central nervous system. We investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE, an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: P. acidilactici R037 was orally administered to EAE mice to investigate the effects of R037. R037 treatment suppressed clinical EAE severity as prophylaxis and therapy. The antigen-specific production of inflammatory cytokines was inhibited in R037-treated mice. A significant increase in the number of CD4(+ Interleukin (IL-10-producing cells was observed in the mesenteric lymph nodes (MLNs and spleens isolated from R037-treated naive mice, while no increase was observed in the number of these cells in the lamina propria. Because only a slight increase in the CD4(+Foxp3(+ cells was observed in MLNs, R037 may primarily induce Foxp3(- IL10-producing T regulatory type 1 (Tr1 cells in MLNs, which contribute to the beneficial effect of R037 on EAE. CONCLUSIONS/SIGNIFICANCE: An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing IL10-producing Tr1 cells. Our findings indicate the therapeutic potential of the oral administration of R037 for treating multiple sclerosis.

  1. Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats.

    Science.gov (United States)

    Ciftci, Osman; Vardi, Nigar; Ozdemir, Ilknur

    2013-03-01

    The objective of current study is to investigate the effects of the administration of chrysin (CH) and quercetin (Q) on rat liver in which oxidative and histological damage had been induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were randomly divided into six equal groups. TCDD was orally administered at the dose of 2 μg/kg/week, and Q and CH were orally administered at the doses of 20 mg/kg day and 50 mg/kg/day, respectively, by gavages dissolved in corn oil. The liver samples to be analyzed for the determination of oxidative and histological alternations were taken from rats at 60 days. The results indicated that although 2,3,7,8-TCDD significantly induced (P ≤ 0.01) lipid peroxidation (increase of MDA levels), it positively affected oxidant/antioxidant system (a decline in the levels of GSH, CAT, GSH-Px, and CuZn-SOD) in rats significantly. The histological changes observed in the liver correlated with the biochemical findings. However, these effects of TCDD on oxidative and histological changes were eliminated by Q and CH treatment. In conclusion, TCDD caused an adverse effect on rat's liver. When Q and CH were given together with TCDD, they prevented hepatotoxicty induced by TCDD. Thus, it is thought that Q and CH may be useful as a new category of anti-TCDD toxicity agent.

  2. Restoration of electric footshock-induced immunosuppression in mice by Gynostemma pentaphyllum components.

    Science.gov (United States)

    Im, Sun-A; Choi, Hyun Sook; Choi, Soon Ok; Kim, Ki-Hyang; Lee, Seungjeong; Hwang, Bang Yeon; Lee, Myung Koo; Lee, Chong Kil

    2012-06-25

    The immunomodulatory effects of the ethanol extract of Gynostemma pentaphyllum (GP-EX) were examined in electric footshock (EFS)-stressed mice. The mice were orally administered various doses of GP-EX for 7 days before exposure to EFS (duration: 3 min, interval: 10 s, intensity: 2 mA) once a day from day 8 for 14 days with continuous daily feeding of GP-EX. Oral administration of GP-EX to mice prevented EFS stress-induced immunosuppression as determined by the lymphoid organ (thymus and spleen) weight and cellularity. In addition, oral administration of GP-EX restored EFS-suppressed functional properties of mature lymphocytes in terms of concanavalin A-induced proliferation of splenocytes and lipopolysaccharide-induced cytokine production (TNF-α, IL-1β). Furthermore, we found that mice that were orally administered with GP-EX generated much more potent ovalbumin-specific cytotoxic T lymphocyte responses upon intravenous ovalbumin injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could increase host defense in immunocompromised situations such as stress-induced immunosuppression.

  3. Restoration of Electric Footshock-Induced Immunosuppression in Mice by Gynostemma pentaphyllum Components

    Directory of Open Access Journals (Sweden)

    Sun-A Im

    2012-06-01

    Full Text Available The immunomodulatory effects of the ethanol extract of Gynostemma pentaphyllum (GP-EX were examined in electric footshock (EFS-stressed mice. The mice were orally administered various doses of GP-EX for 7 days before exposure to EFS (duration: 3 min, interval: 10 s, intensity: 2 mA once a day from day 8 for 14 days with continuous daily feeding of GP-EX. Oral administration of GP-EX to mice prevented EFS stress-induced immunosuppression as determined by the lymphoid organ (thymus and spleen weight and cellularity. In addition, oral administration of GP-EX restored EFS-suppressed functional properties of mature lymphocytes in terms of concanavalin A-induced proliferation of splenocytes and lipopolysaccharide-induced cytokine production (TNF-α, IL-1β. Furthermore, we found that mice that were orally administered with GP-EX generated much more potent ovalbumin-specific cytotoxic T lymphocyte responses upon intravenous ovalbumin injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could increase host defense in immunocompromised situations such as stress-induced immunosuppression.

  4. Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection.

    Science.gov (United States)

    Shi, Shao-Hua; Yang, Wen-Tao; Yang, Gui-Lian; Zhang, Xu-Ke; Liu, Yu-Ying; Zhang, Li-Jiao; Ye, Li-Ping; Hu, Jing-Tao; Xing, Xin; Qi, Chong; Li, Yu; Wang, Chun-Feng

    2016-01-01

    Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs.

  5. Dose-response investigation of oral ketoprofen in pigs challenged with Escherichia coli endotoxin.

    Science.gov (United States)

    Mustonen, K; Banting, A; Raekallio, M; Heinonen, M; Peltoniemi, O A T; Vainio, O

    2012-07-21

    In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B(2) and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B(2) concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.

  6. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    Science.gov (United States)

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice.

  7. Treatment of 60 Cases of Gouty Arthritis with Modified Simiao Tang

    Institute of Scientific and Technical Information of China (English)

    Qiu Renbin; Shen Ruizi; Lin Dejiu; Chen Yuanlin; Ye Hongping; Zhu Hanting

    2008-01-01

    Objective:To observe the clinical effect of a modified Simiao Tang(加味四妙汤 Modified Decoction of Four Wonderful Drugs)for gouty arthritis and its influence on uric acid in blood.Methods:120 cases of gouty arthritis were randomly divided into the treatment group and control group with 60 cases in each group.Modified Simiao Tang(MST)was orally administered to the patients in the treatment group and allopurinol tablet was orally administered to the patients in the control group.The clinical effects of two groups were evaluated after one-week treatment and uric acid(UA)and C-reactive protein(CRP)levels in blood were determined after 1-month treatment.Results:The total effective rate in the treatment group was significantly higher than in the control group,86.7%vs.68.3%(P<0.01).And the treatment group was also significantly better than the control group in decreasing UA and CRP(P<0.05 or P<0.01).Conclusions:MST can significantly improve the symptoms and signs of gouty arthritis and decrease the levels of UA and CRP It is good for gouty arthritis.

  8. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

    Science.gov (United States)

    Ismail, Iza Farhana; Abdul Majid, Nazia; Kadir, Farkaad A.; Al-Bayaty, Fouad; Awang, Khalijah

    2012-01-01

    Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer. PMID:23365597

  9. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Iza Farhana Ismail

    2012-01-01

    Full Text Available Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS stains, levels of lipid peroxidation, malondialdehyde (MDA, antioxidant enzymes, and superoxide dismutase (SOD were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.

  10. Oral Nanostructured Lipid Carriers Loaded with Near-Infrared Dye for Image-Guided Photothermal Therapy.

    Science.gov (United States)

    Chen, Gang; Wang, Kaikai; Zhou, Yiwen; Ding, Ling; Ullah, Aftab; Hu, Qi; Sun, Minjie; Oupický, David

    2016-09-28

    Photothermal therapy exerts its anticancer effect by converting laser radiation energy into hyperthermia using a suitable photosensitizer. This study reports development of nanostructured lipid carriers (NLCs) suitable for noninvasive oral delivery of a near-infrared photosensitizer dye IR780. The carrier encapsulating the dye (IR780@NLCs) was stable in simulated gastric and intestinal conditions and showed greatly enhanced oral absorption of IR780 when compared with the free dye. As a result of increased oral bioavailability, enhanced accumulation of the dye in subcutaneous mouse colon tumors (CT-26 cells) was observed following oral gavage of IR780@NLCs. Photothermal antitumor activity of orally administered IR780@NLCs was evaluated following local laser irradiation of the CT-26 tumors. We observed significant effect of the photothermal IR780@NLCs treatment on the rate of the tumor growth and no toxicity associated with the oral administration of IR780@NLCs. Overall, orally administered IR780@NLCs represents a safe and noninvasive method to achieve systemic tumor delivery of a photosensitizing dye for applications in photothermal anticancer therapies.

  11. Transepithelial Transport of Fc -Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery

    Science.gov (United States)

    Pridgen, Eric M.; Alexis, Frank; Kuo, Timothy T.; Levy-Nissenbaum, Etgar; Karnik, Rohit; Blumberg, Richard S.; Langer, Robert; Farokhzad, Omid C.

    2014-01-01

    Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. Here, we show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which is known to mediate the transport of IgG antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*h compared with only 1.2%*h for non-targeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating the enhanced nanoparticle transport was due specifically to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration. PMID:24285486

  12. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

    Directory of Open Access Journals (Sweden)

    Sena Lee

    2014-04-01

    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  13. Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats

    DEFF Research Database (Denmark)

    OA, Andreassen; Weber, Christine; HA, Jorgensen

    1999-01-01

    dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL...... significantly increased the level of oral dyskinesias, and the increase persisted for 12 weeks after drug withdrawal. Cotreatment with CoQ10 did not attenuate the development of HAL-induced oral dyskinesia. Despite adequate absorption of orally administered CoQ10, shown by the increased serum levels of CoQ10......, no increase of either CoQ10 or coenzyme Q9 was detected in the brain. These results suggest that cotreatment with CoQ10 does not inhibit the development of HAL-induced oral dyskinesias in rats, and that further studies seem to be needed in order to clarify the pharmakokinetics of CoQ10 in rats...

  14. Galactoglucomannan-rich hemicellulose extract from Norway spruce (Picea abies) exerts beneficial effects on chronic prostatic inflammation and lower urinary tract symptoms in vivo.

    Science.gov (United States)

    Konkol, Yvonne; Vuorikoski, Heikki; Tuomela, Johanna; Holmbom, Bjarne; Bernoulli, Jenni

    2017-08-01

    Galactoglucomannan (GGM) is the main hemicellulose class in wood of coniferous trees and could be potentially utilized as a possible health-promoting substance for food and pharmaceutical industry. Our aim was to evaluate effects of orally administered GGM-rich extract from Norway spruce in a rat model of chronic prostatitis associated with lower urinary tract symptoms (LUTS). Prostatic inflammation and LUTS was induced in male rats using testosterone and 17β-estradiol exposure for 18 weeks. Rats were treated with 2% GGM dissolved in drinking water during weeks 13-18. Pelvic pain response, LUT function and histopathological evaluation of the prostate were assessed. The results show that hormonal exposure induced LUTS seen as decreased urine flow rate, increased bladder pressure, voiding times, bladder capacity and residual urine volumes. GGM had positive effects on urodynamical parameters by decreasing the basal bladder pressure, increasing the urine flow rate and volume, reducing the residual volume and increasing micturition intervals. GGM reduced the extent of the hormone exposure-induced prostatic inflammation. Increase of pelvic pain induced by hormone exposure was only slightly affected by GGM treatment. The results suggest that orally administered GGM may have potential usage for improving lower urinary tract function associated with chronic prostatic inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats

    Directory of Open Access Journals (Sweden)

    Gehan Moustafa Badr

    2014-01-01

    Full Text Available Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE on indomethacin-(IN- induced gastric inflammation in male rats. Animals were divided into six groups (n=8 control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA, myeloperoxidase (MPO, tumor necrosis factor-α (TNF-α values, and the significant decrease in the total glutathione (tGSH, superoxide dismutase (SOD, and catalase (CAT values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.

  16. Potential for tyndalized Lactobacillus acidophilus as an effective component in moisturizing skin and anti-wrinkle products.

    Science.gov (United States)

    Im, A-Rang; Kim, Hui Seong; Hyun, Jin Won; Chae, Sungwook

    2016-08-01

    It is widely accepted that ultraviolet (UV) irradiation induces skin damage. In the present study, a UVB-induced hairless mouse model of skin photoaging was developed to determine whether tyndalized Lactobacillus acidophilus was able to significantly enhance the repair of photodamaged skin. To evaluate the effects of tyndalized L. acidophilus on UVB-induced skin-wrinkle formation in vivo, HR-1 hairless male mice were exposed to UVB radiation and orally administered tyndalized L. acidophilus. Compared with the control group, the UVB irradiation mice displayed a significant increase in transepidermal water loss and a reduction in skin hydration. In mice with UVB-induced photodamage, the effacement of the fine wrinkles by tyndalized L. acidophilus was correlated with dermal collagen synthesis, accompanied by histological changes. Furthermore, western blotting was performed to investigate the protein expression levels of matrix metalloproteinases (MMPs) and mitogen-activated protein kinase. Notably, orally administered tyndalized L. acidophilus reduced the expression levels of MMP-1 and MMP-9. Based upon the aforementioned results, it was determined that tyndalized L. acidophilus effectively inhibited the wrinkle formation induced by UVB irradiation, and that this may be attributed to the downregulation of MMPs. Therefore, tyndalized L. acidophilus may be considered a potential agent for preventing skin photoaging and wrinkle formation.

  17. Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds.

    Science.gov (United States)

    Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A V

    2012-01-01

    Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption.

  18. Oral administration of Lactobacillus casei variety rhamnosus partially alleviates TMA-induced atopic dermatitis in mice through improving intestinal microbiota.

    Science.gov (United States)

    Yeom, M; Sur, B J; Park, J; Cho, S G; Lee, B; Kim, S T; Kim, K S; Lee, H; Hahm, D H

    2015-08-01

    The purpose of this study was to investigate the effect of Lactobacillus casei variety rhamnosus (LCR35) on Atopic dermatitis (AD)-like symptoms in mice. AD-like skin lesions in BALB/C mice were induced by sensitization and subsequent repeated challenges with trimellitic anhydride (TMA) for 10 days. LCR35 was orally administered to the mice once daily throughout the study. In the TMA-induced AD model, orally administered LCR35 suppressed significantly irritant-related scratching behaviour and skin dehydration as well as apparent severity of AD. LCR35 also significantly decreased serum levels of IgE and IL-4, but not IFN-γ, implying the restoration of TMA-induced disruption of Th1/Th2 balance. Quantitative real-time PCR targeting hypervariable regions of 16S rDNA gene of faecal microbiota indicated that the LCR35 treatment increased the population of Bifidobacterium, Lactobacilli, Enterococcus and Bacteroides fragilis group, but decreased those of Clostridium coccoides group. LCR35 has the ability to suppress the development of AD in mice, possibly through the modulation of Th1/Th2 balance and gut microbiota. LCR35 has a strong potential as a probiotic for preventing AD. © 2015 The Society for Applied Microbiology.

  19. Short communication. Enhancement of the immune responses to vaccination against foot-and-mouth disease in mice by oral administration of Quillaja saponaria-A and extracts of Cochinchina momordica seed

    Directory of Open Access Journals (Sweden)

    C. W. Xiao

    2013-02-01

    Full Text Available This study was designed to evaluate the effects of oral administration of extracts from Cochinchina momordica seed (ECMS or Quillaja saponaria-A (Quil-A on the immune responses in mice immunized with foot and mouth disease virus (FMDV-serotype O vaccine. Forty-two imprinting control region (ICR mice were randomly divided into seven groups of 6 animals in each group, and a dose of 400 μg of Quil-A or ECMS was orally administered for 1,, 2 or 3 days. After that, the animals were subcutaneously immunized twice with FMD vaccine at 3-week intervals and blood samples were collected 2-weeks after boosting for measurement of FMDV-specific IgG and its subclasses. Spleens were collected for lymphocytes proliferation assay. Results indicated that serum FMDV-specific IgG and the IgG subclass responses were significantly enhanced in mice orally administered ECMS or Quil-A when compared with the control group (p<0.05. Lymphocytes proliferation response to FMD vaccine was significantly enhanced by ECMS compared with the control (p<0.05. This study illustrates that ECMS induced immunomodulatory effects and performed better than Quil-A.

  20. Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

    Science.gov (United States)

    Burnett, A; McKoy, M-L; Singh, P

    2015-01-01

    ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580