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Sample records for orally-administered glycyrrhizic acid-treated

  1. Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Souza, Marcy J; Greenacre, Cheryl B; Cox, Sherry K

    2008-08-01

    To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus). 6 healthy adult sexually intact female New Zealand White rabbits. Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol). No adverse effects were detected after oral administration of tramadol to rabbits. Mean +/- SD half-life of tramadol after administration was 145.4 +/- 81.0 minutes; mean +/- SD maximum plasma concentration was 135.3 +/- 89.1 ng/mL. Although the dose of tramadol required to provide analgesia in rabbits is unknown, the dose administered in the study reported here did not reach a plasma concentration of tramadol or O-desmethyltramadol that would provide sufficient analgesia in humans for clinically acceptable periods. Many factors may influence absorption of orally administered tramadol in rabbits.

  2. Developmental toxicity of orally administered pineapple leaf extract in rats.

    Science.gov (United States)

    Hu, Jun; Lin, Han; Shen, Jia; Lan, Jiaqi; Ma, Chao; Zhao, Yunan; Lei, Fan; Xing, Dongming; Du, Lijun

    2011-06-01

    The extract of pineapple leaves (EPL) has anti-diabetic and anti-dyslipidemic effects and can be developed into a promising natural medicine. This study was conducted to evaluate EPL's effects on developmental parameters in order to provide evidence of its safety before potential medical use. Five groups were included: a negative control that was given distilled water daily, a positive control that was dosed 7 mg/kg cyclophosphamide (CP) every two days, and three groups that were respectively dosed 2.0, 1.0, and 0.5 g/kg EPL daily. Female rats were dosed during the organogenesis period of gestation days (GD) 7-17 and terminated on GD 20. A series of parameters were examined. Data revealed that CP significantly reduced maternal body weight gains, caused maternal organ weight alterations, reduced female fertility, disturbed fetal growth and development, and caused marked teratogenic effects on fetal appearances, skeleton and internal organs. Distilled water and the three high doses of EPL did not cause any of the aforementioned effects. This study concluded that orally administered EPL is safe to rats during embryonic development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  4. Radiosynthesis of 123I-labeled hesperetin for biodistribution study of orally administered hesperetin

    International Nuclear Information System (INIS)

    Jongho Jeon; So-Young Ma; Dae Seong Choi; Beom-Su Jang; Jung Ae Kang; You Ree Nam; Seonhye Yoon; Sang Hyun Park; Korea University of Science and Technology, Daejeon

    2015-01-01

    The purpose of this study is to synthesize 123 I-labeled hesperetin and to investigate its in vivo behavior. The optimized labeling condition provided two isomers of 123 I-labeled hesperetin with high radiochemical yields and radiochemical purities. Both 123 I-labeled products were orally administered to normal ICR mice, and the initial result showed that most of 123 I activity was detected in the stomach and the intestines. A part of 123 I-labeled hesperetin was absorbed from the small intestine to bloodstream and then it was distributed in normal organs. The results in the present study provided an efficient radiolabeling method of flavonoid and quantitative organ distribution of orally administered hesperetin. (author)

  5. Radiation dose calculations for orally administered radio-pharmaceuticals in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Wu, R.K.; Malmud, L.S.; Knight, L.C.; Siegel, J.A.; Stern, H.; Zelac, R.

    1983-01-01

    Radiation burden estimates for upper gastrointestinal function studies employing the following orally administered radiopharmaceuticals are reported. Technetium 99m sulfur colloid (Tc-99m-SC) in water, Indium-111-DTPA in water, Tc-99m-DTPA in water, Indium-113m DTPA in water, Tc-99m Ovalbumin, Tc-99m sulfur colloid in a cooked egg, Tc-99m sulfur colloid in vivo labeled chicken liver, and Indium-111 colloid in vivo labeled chicken liver. Orally administered radiopharmaceuticals for upper gastrointestinal studies afford clinician and investigator valuable clinical and physiologic information not previously obtainable using other techniques. The radiation burden to the patient from single or sequential studies is acceptable in comparison to fluoroscopy which results in approximately 5000 millirem per minute of exposure. The variety of preparations listed above should make these types of studies available in any routinely equipped nuclear medicine radiopharmacy laboratory

  6. Extraction of Glycyrrhizic Acid and Glabridin from Licorice

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    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.

  7. The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients.

    Science.gov (United States)

    Malingré, M M; Schellens, J H; Van Tellingen, O; Ouwehand, M; Bardelmeijer, H A; Rosing, H; Koopman, F J; Schot, M E; Ten Bokkel Huinink, W W; Beijnen, J H

    2001-11-16

    The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(-2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(-2), for the other three 15 ml m(-2). Prior to paclitaxel administration patients received 15 mg kg(-1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C(max)) and area under the concentration-time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(-2), paclitaxel C(max) and AUC values were 0.10 +/- 0.06 microM and 1.29 +/- 0.99 microM h(-1), respectively, whereas these values were 0.31 +/- 0.06 microM and 2.61 +/- 1.54 microM h(-1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(-2), paclitaxel excretion in faeces was 38.8 +/- 13.0% of the administered dose, whereas this value was 18.3 +/-15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel

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

    Science.gov (United States)

    Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin

    2014-01-01

    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 distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict

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

    Directory of Open Access Journals (Sweden)

    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

  10. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.

    Science.gov (United States)

    Bagchi, D; Misner, B; Bagchi, M; Kothari, S C; Downs, B W; Fafard, R D; Preuss, H G

    2002-01-01

    Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the

  11. Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice.

    Science.gov (United States)

    Nakanishi, Tomonori; Tokunaga, Yuzo; Yamasaki, Masao; Erickson, Laurie; Kawahara, Satoshi

    2016-12-01

    Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-γ production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis. © 2016 Japanese Society of Animal Science.

  12. 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.

  13. Total body retention of orally administered 47Ca in primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Mallette, L.E.; Sode, J.E.; Marx, S.J.; Georges, L.P.; Aurbach, G.D.

    1975-01-01

    Using a whole-body radiation detector, the total-body retention of 47 Ca 7 days after oral administration of the isotope to patients with various disorders of calcium metabolism was measured. The percent retention of 47 Ca given with 90 mg of unlabeled (carrier) calcium varied with the calcium metabolic status as follows: normals (n = 14), 33--43 percent (mean 38); primary hyperparathyroidism (n = 28), 32--74 percent (mean 52); idiopathic hypercalciuria (n = 9), 34--49 percent (mean 42); and hypercalcemia of other etiology (n = 3), 23--26 percent (mean 25). Almost half (13/28) of those with hyperparathyroidism showed a retention above 55 percent, distinguishing them from subjects with idiopathic hypercalciuria. Retention of 47 Ca correlated poorly with clinical measures of severity of hyperparathyroidism. When isotope was diluted with a smaller amount of carrier calcium (20 mg), retention was increased in normals (n = 5) to 46--54 percent (mean 50) and in hyperparathyroidism (n = 5) to 64--87 percent (mean 73). After surgical cure of hyperparathyroidism retention of isotope returned toward normal in 5 of 7 subjects. Whole-body retention of orally administered 47 Ca may prove useful in detecting hyperparathyroidism in subjects with mild hypercalcemia or hypercalciuria. (U.S.)

  14. Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs.

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    Raekallio, Marja R; Honkavaara, Juhana M; Säkkinen, Mia S; Peltoniemi, S Marikki

    2007-04-01

    To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. 6 neutered male Beagles. Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

  15. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

    Science.gov (United States)

    Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

    2016-01-01

    To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

  16. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

    Science.gov (United States)

    Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

    2017-01-01

    Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

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

    Science.gov (United States)

    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.

  18. Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation.

    Science.gov (United States)

    Afonso, T; Giguère, S; Brown, S A; Barton, M H; Rapoport, G; Barba, M; Dembek, K A; Toribio, R E; Coleman, A E

    2017-10-17

    Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. Prospective, randomised double-blind, placebo-controlled trial. Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. Very small sample size and short treatment period. Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is

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

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    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.

  20. 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.

  1. A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

    OpenAIRE

    Fritz, Sara; Henson, Michael; Greengard, Emily; Winter, Amber; Stuebner, Kathleen; Yoon, Una; Wilk, Vicki; Borgatti, Antonella; Augustin, Lance; Modiano, Jaime; Saltzman, Daniel

    2017-01-01

    Abstract We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of do...

  2. 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.

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

    International Nuclear Information System (INIS)

    Huang Yun; Cui Lijian; Wang Jianming; Huo Kun; Chen Chen; Zhan Wenhong; Wang Yongli

    2012-01-01

    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: ► Effect of atropine or glycyrrhizic acid on aconitine–BSA binding. ► UV–vis absorption and fluorescence spectroscopic techniques used. ► Aconitine quenched BSA fluorescence via dynamic quenching with r=2.62 nm. ► Atropine sulphate and glycyrrhizic acid decreased K A and n of aconitine–BSA. ► Support for aconitine detoxification by atropine and glycyrrhizic acid.

  4. 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...

  5. Orally administered sodium 4-phenylbutyrate suppresses the development of dextran sulfate sodium-induced colitis in mice.

    Science.gov (United States)

    Ono, Kazuhiko; Nimura, Satoshi; Hideshima, Yuko; Nabeshima, Kazuki; Nakashima, Manabu

    2017-12-01

    Sodium 4-phenylbutyrate (PBA) exerts therapeutic effects in a wide range of pathologies. A previous study by the present authors revealed that intraperitoneal administration of PBA suppresses the onset of dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, the effects of orally administered PBA are investigated, as this route of administration is more clinically relevant. The therapeutic efficacy of PBA (10 mg/12 h) in mice with experimental colitis was assessed based on the disease activity index, production of inflammatory cytokines, colon length and histopathological investigations. The results of the present study demonstrated a significantly higher survival rate in the PBA-treated group compared with the PBA-untreated (DSS control) group (P=0.0156). PBA treatment improved pathological indices of experimental colitis (P<0.05). Furthermore, the oral administration of PBA significantly inhibited the DSS-induced shortening of the colon (P<0.05) and overproduction of interleukin (IL)-1β and IL-6 (both P<0.05) as measured in colonic lavage fluids. A marked attenuation of the DSS-induced overproduction of tumor necrosis factor was also observed. For histopathological analysis, a marked decrease in mature goblet cells and increase in enlarged nuclei of the absorptive cells was observed in colon lesions of DSS control mice as compared with normal untreated mice. However, in the PBA-treated mice, no such lesions were observed and the mucosa resembled that of DSS-untreated mice. The results of the present study, combined with those results of a previous study, suggest that oral and intraperitoneal administration of PBA have similar preventative effects on DSS-induced colitis, achieved by suppressing its pathogenesis.

  6. 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.

  7. Comparative tissue distribution and excretion of orally administered [3H]diacetoxyscirpenol (anguidine) in rats and mice

    International Nuclear Information System (INIS)

    Wang, J.S.; Busby, W.F. Jr.; Wogan, G.N.

    1990-01-01

    A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content or the absorption, metabolism, or excretion of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity instead, the carcass and skin dropped from the top rank tissues at 90 min and were replaced by the spleen and cecum. At 24 hr and 7 days the top-ranked order of tissues shifted to include organs associated with trichothecene-induced toxicity such as the lymphohematopoietic system (spleen, thymus, and femur bone marrow), heart, and testis (in mouse) as well as the cecum and large intestine. In addition, the rate of loss of radioactivity with time generally did not decrease as rapidly in these target organs as observed in liver, kidney, skin, and carcass. Brain radioactivity, though very low, also diminished relatively slowly. Significant differences in specific radioactivity which did occur between the rat and mouse tended to occur in target organs and with the higher levels present in the mouse. These data were discussed in terms of interspecies differences in lethality and target organ toxicity

  8. Presence of orally administered rice bran oil γ-oryzanol in its intact form in mouse plasma.

    Science.gov (United States)

    Kobayashi, Eri; Ito, Junya; Kato, Shunji; Sawada, Kazue; Matsuki, Midori; Hashimoto, Hiroyuki; Miyazawa, Teruo; Nakagawa, Kiyotaka

    2016-12-07

    Although the beneficial effects (e.g., lipid-lowering activity) of γ-oryzanol (OZ), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, have been extensively investigated, few studies have evaluated the absorption and metabolism of OZ. Moreover, it is unclear whether OZ, once ingested, is directly absorbed by the intestine into the bloodstream at a sufficient level to exhibit activity. Here, we prepared OZ concentrate from purified rice bran oil (Rice Oil OZ), determined the concentration of OZ in the preparation (cycloartenyl ferulate equivalent concentration; 52.2%), and then carried out chromatography-mass spectrometry analysis of plasma samples from mice after oral administration of Rice Oil OZ. The OZ concentrations of plasma from the control (vehicle-treated) mice were low (trace levels); however, at 5 h after a single oral administration of the Rice Oil OZ (600 mg per kg body weight), the levels significantly increased, reaching 17.6 ng mL -1 for cycloartenyl ferulate, 28.2 ng mL -1 for 24-methylenecycloartanyl ferulate isomers, 15.6 ng mL -1 for campesteryl ferulate, and 5.1 ng mL -1 for β-sitosteryl ferulate, respectively, expressed in equivalence of cycloartenyl ferulate in plasma. These results provided the first mass spectrometric evidence suggesting that a portion of orally administered OZ is directly absorbed by the intestine and is present in the intact form in plasma. The presence of a significant amount of OZ in its intact form in plasma may explain the beneficial effects of OZ in vivo.

  9. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

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

    African Journals Online (AJOL)

    Fluoride in drinking water above permissible levels is responsible for dental and skeletal fluorosis. In this study, removal of fluoride ions from water using phosphoric acid treated lime was investigated in continuous and point-of-use system operations. In the continuous column operations, fluoride removal performance was ...

  11. Resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles: Preparation, characterization, and targeting effect on liver tumors.

    Science.gov (United States)

    Wu, Mingfang; Lian, Bolin; Deng, Yiping; Feng, Ziqi; Zhong, Chen; Wu, Weiwei; Huang, Yannian; Wang, Lingling; Zu, Chang; Zhao, Xiuhua

    2017-08-01

    In this study, glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were prepared to establish a tumor targeting nano-sized drug delivery system. Glycyrrhizic acid was coupled to human serum albumin, and resveratrol was encapsulated in glycyrrhizic acid-conjugated human serum albumin by high-pressure homogenization emulsification. The average particle size of sample nanoparticles prepared under the optimal conditions was 108.1 ± 5.3 nm with a polydispersity index (PDI) of 0.001, and the amount of glycyrrhizic acid coupled with human serum albumin was 112.56 µg/mg. The drug encapsulation efficiency and drug loading efficiency were 83.6 and 11.5%, respectively. The glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were characterized through laser light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, and gas chromatography. The characterization results showed that resveratrol in glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles existed in amorphous state and the residual amounts of chloroform and methanol in nanoparticles were separately less than the international conference on harmonization (ICH) limit. The in vitro drug-release study showed that the nanoparticles released the drug slowly and continuously. The inhibitory rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide method. The IC50 values of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles and resveratrol were 62.5 and 95.5 µg/ml, respectively. The target ability of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles

  12. Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study.

    Science.gov (United States)

    Cadarette, Suzanne M; Lévesque, Linda; Mamdani, Muhammad; Perreault, Sylvie; Juurlink, David N; Paterson, J Michael; Carney, Greg; Gunraj, Nadia; Hawker, Gillian A; Tadrous, Mina; Wong, Lindsay; Dormuth, Colin R

    2013-09-01

    Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults. We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis. We identified 321 755 patients who were eligible for inclusion in the study. We found little difference in fracture rates between men (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74-1.14) or women (pooled HR 1.15, 95% CI 0.73-1.56) taking risedronate and those taking alendronate. We similarly identified little difference in fracture rates between women taking etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82-1.18). However, we identified lower rates of hip fracture among men taking etidronate relative to alendronate (pooled HR 0.77, 95% CI 0.60-0.94). Results extended to 2 and 3 years' follow-up were similar. However, with 3 years' follow-up, rates of hip fracture were lower among women in British Columbia who had taken alendronate. We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our finding that etidronate is associated with lower fracture risk among men is likely due to

  13. Intestinal absorption and biliary elimination of glycyrrhizic acid diethyl ester in rats

    Directory of Open Access Journals (Sweden)

    Koga K

    2013-10-01

    Full Text Available Kenjiro Koga,1 Mayuri Kawamura,1 Hiroshi Iwase,2 Nobuji Yoshikawa31Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, 2Research Division, 3Research and Development Division, Cokey Systems Co, Ltd, Matsusaka, JapanBackground: The purpose of this study was to evaluate absorption and elimination from the gastrointestinal tract of glycyrrhizic acid diethyl ester (GZ-DE which was prepared as a prodrug of glycyrrhizic acid (a poorly absorbed compound in rats.Methods: After the GZ-DE solution was administered via the intravenous, intraduodenal, intraileal, and stomach routes, GZ-DE and GZ concentrations in bile were determined by high-performance liquid chromatography. The stability of GZ-DE was estimated from residual GZ-DE and GZ produced in GZ-DE solutions prepared with distilled water, a pH 1.2 solution, 0.9% NaCl solution, and phosphate-buffered solution (pH 7.4 at 37°C.Results: GZ-DE was eliminated into bile by the pharmacokinetic parameters of apparent distribution rate constant (4.56 ± 0.36 per hour and apparent elimination rate constant (0.245 ± 0.042 per hour. After intravenous and intraduodenal administration of GZ-DE, the concentration ratio of GZ-DE to GZ in bile was approximately 4:1, and the bioavailability of GZ containing GZ-DE was three-fold higher compared with the bioavailability of GZ after intraduodenal administration. GZ-DE was immediately precipitated in pH 1.2 solution and was converted to GZ by hydrolysis in pH 7.4 solution.Conclusion: Improvement of intestinal absorption of GZ was made possible by administration of GZ-DE into the intestine where absorption of GZ is lower than in the strong acidic environment of the stomach. However, because the elimination rate in bile simulated from kinetic parameters of GZ-DE was higher than the conversion rate from GZ-DE to GZ by hydrolysis, it is thought that the availability of GZ as a revolutionary prodrug was not high from the

  14. Immunogenicity in chickens with orally administered recombinant chicken-borne Lactobacillus saerimneri expressing FimA and OmpC antigen of O78 avian pathogenic Escherichia coli.

    Science.gov (United States)

    Ma, Sun-Ting; Ding, Guo-Jie; Huang, Xue-Wei; Wang, Zi-Wei; Wang, Li; Yu, Mei-Ling; Shi, Wen; Jiang, Yan-Ping; Tang, Li-Jie; Xu, Yi-Gang; Li, Yi-Jing

    2018-03-01

    Avian colibacillosis is responsible for economic losses to poultry producers worldwide. To combat this, we aimed to develop an effective oral vaccine for chicken against O78 avian pathogenic Escherichia coli (APEC) infection through a Lactobacillus delivery system. Eight Lactobacillus strains isolated from the intestines of broiler chickens were evaluated based on their in vitro adherence ability to assess their potential as a delivery vector. Fimbrial subunit A (FimA) and outer-membrane protein C (OmpC) of APEC with and without fusion to dendritic cell-targeting peptide (DCpep) and microfold cell-targeting peptide (Co1) were displayed on the surface of Lactobacillus saerimneri M-11 and yielded vaccine groups (pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, respectively). The colonization of the recombinant strains in vivo was assessed and the immunogenicity and protective efficacy of orally administered recombinant strains in chickens were evaluated. The colonization of the recombinant strains in vivo revealed no significant differences between the recombinant and wild-type strains. Chickens orally administered with vaccine groups showed significantly higher levels of OmpC/FimA-specific IgG in serum and mucosal IgA in cecum lavage, nasal lavage and stool compared to the pPG/M-11 group. After challenge with APEC CVCC1553, better protective efficacy was observed in chickens orally immunized with pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, but no significant differences were observed between the two groups. Recombinant chicken-borne L. saerimneri M-11 showed good immunogenicity in chickens, suggesting that it may be a promising vaccine candidate against APEC infections. However, the activity of mammalian DCpep and Co1 was not significant in chickens.

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

    Directory of Open Access Journals (Sweden)

    Jenneke Leentjens

    Full Text Available 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.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.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.The present study does not support the use of oral β-glucan to enhance innate immune responses in humans.ClinicalTrials.gov NCT01727895.

  16. Effect of orally-administered Lactobacillus plantarum LPLM-O1 strain in an immunosuppressed mouse model of urinary tract infection.

    Science.gov (United States)

    de Arellano, A Ramírez; Sánchez, M; Vera, R; Jara, S; González, M; Castro, E

    2012-03-01

    Urinary tract infections (UTIs) affect both healthy and immunocompromised people, and they are treated with antibiotics. However, the high recurrence of UTIs obliges the use of natural mechanisms to regulate the normal microbiota through the use of e.g. lactic acid bacteria. In order to induce a UTI, 20 µl of the Escherichia coli (Ec-01) strain, in doses of 2.7×10(7) cfu/ml, was inoculated by way of the urethra in female Balb/c mice, all of them immunosuppressed with dexamethasone (10 mg/kg). Lactobacillus plantarum LPLM-O1 was used as a treatment, in daily doses of 1×10(7) cfu/ml, which were orally administered for seven days before the infection (preventive) or alongside the infection for seven days (curative). The oral administration of LPLM-O1 did not cause any adverse effects when used in an immunosuppressed animal model. It was observed that, when used as a preventive measure, LPLM-O1 induces a decrease in the infection, in the concentration of urinary leukocytes, and in the bacterial load. This study proposes the use of this lactic bacterium as a probiotic.

  17. Extraction of Glycyrrhizic Acid from Glycyrrhiza uralensis Using Ultrasound and Its Process Extraction Model

    Directory of Open Access Journals (Sweden)

    Jiangqing Liao

    2016-10-01

    Full Text Available This work focused on the intensification of extraction process of glycyrrhizic acid (GA from Glycyrrhiza uralensis using ultrasound-assisted extraction (UAE method. Various process parameters such as ultrasonic power, ultrasonic frequency, extraction temperature, and extraction time which affect the extraction yield were optimized. The results showed that all process parameters had exhibited significant influences on the GA extraction. The highest GA yield of 217.7 mg/g was obtained at optimized parameters of 125 W, 55 kHz, 25 °C, and 10 min. Furthermore, the extraction kinetics model of this process was also investigated based on Fick’s first law available in the literature. Kinetic parameters such as equilibrium concentration (Ce and integrated influence coefficient (λ for different ultrasonic powers, ultrasonic frequencies, and extraction temperatures were predicted. Model validations were done successfully with the average of relative deviation between 0.96% and 4.36% by plotting experimental and predicted values of concentration of GA in extract. This indicated that the developed extraction model could reflect the effectiveness of the extraction of GA from Glycyrrhiza uralensis and therefore serve as the guide for comprehending other UAE process.

  18. Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Sun, Xue; Duan, Xingping; Wang, Changyuan; Liu, Zhihao; Sun, Pengyuan; Huo, Xiaokui; Ma, Xiaodong; Sun, Huijun; Liu, Kexin; Meng, Qiang

    2017-07-05

    Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism investigation indicated that GA reduced hepatic lipogenesis via downregulating SREBP-1c, FAS and SCD1 expression, increased fatty acids β-oxidation via an increase in PPARα, CPT1α and ACADS, and promoted triglyceride metabolism through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through repressing PEPCK and G6Pase, and increased glycogen synthesis through an induction in gene expression of PDase and GSK3β. In addition, GA increased insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In conclusion, GA produces protective effect against NAFLD, due to regulation of genes involved in lipid, glucose homeostasis and insulin sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [Studies on interaction of acid-treated nanotube titanic acid and amino acids].

    Science.gov (United States)

    Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang

    2010-06-01

    Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.

  20. Out-of-Pocket and Health Care Spending Changes for Patients Using Orally Administered Anticancer Therapy After Adoption of State Parity Laws.

    Science.gov (United States)

    Dusetzina, Stacie B; Huskamp, Haiden A; Winn, Aaron N; Basch, Ethan; Keating, Nancy L

    2017-11-09

    Oral anticancer medications are increasingly important but costly treatment options for patients with cancer. By early 2017, 43 states and Washington, DC, had passed laws to ensure patients with private insurance enrolled in fully insured health plans pay no more for anticancer medications administered by mouth than anticancer medications administered by infusion. Federal legislation regarding this issue is currently pending. Despite their rapid acceptance, the changes associated with state adoption of oral chemotherapy parity laws have not been described. To estimate changes in oral anticancer medication use, out-of-pocket spending, and health plan spending associated with oral chemotherapy parity law adoption. Analysis of administrative health plan claims data from 2008-2012 for 3 large nationwide insurers aggregated by the Health Care Cost Institute. Data analysis was first completed in 2015 and updated in 2017. The study population included 63 780 adults living in 1 of 16 states that passed parity laws during the study period and who received anticancer drug treatment for which orally administered treatment options were available. Study analysis used a difference-in-differences approach. Time period before and after adoption of state parity laws, controlling for whether the patient was enrolled in a plan subject to parity (fully insured) or not (self-funded, exempt via the Employee Retirement Income Security Act). Oral anticancer medication use, out-of-pocket spending, and total health care spending. Of the 63 780 adults aged 18 through 64 years, 51.4% participated in fully insured plans and 48.6% in self-funded plans (57.2% were women; 76.8% were aged 45 to 64 years). The use of oral anticancer medication treatment as a proportion of all anticancer treatment increased from 18% to 22% (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% CI, 0.96-1.13; P = .34) comparing months before vs after parity. In plans subject to parity laws, the

  1. 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 (PLavandula oil 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.

  2. Glycyrrhizic acid attenuates growth of Leishmania donovani by depleting ergosterol levels.

    Science.gov (United States)

    Dinesh, Neeradi; Neelagiri, Soumya; Kumar, Vinay; Singh, Sushma

    2017-05-01

    In the present study, glycyrrhizic acid (GA) the main component of Glycyrrhiza glabra was evaluated for its efficacy as antileishmanial agent and its mode of action explored. GA inhibits promastigotes and intracellular amastigotes in a dose dependent manner at an IC 50 value of 34 ± 3.0 μM and 20 ± 4.2 μM respectively. GA was non-toxic against THP-1 macrophage host cell line. GA was found to inhibit recombinant Leishmania donovani HMG-CoA reductase (LdHMGR) enzyme at the half-maximum inhibitory concentration of 24 ± 4.3 μM indicating the sensitivity and specificity of GA towards the enzyme. However, GA could cause only 30% reduction in HMGR activity when measured in Leishmania promastigotes treated with 34 μM of GA. Interestingly western blot analysis revealed fivefold reduced HMGR expression in GLA treated promastigotes. To further study the mode of action of GA, we used transgenic parasites overexpressing LdHMGR. Results indicated that ∼2 fold resistance was exhibited by LdHMGR overexpressing promastigotes to GA with an IC 50 value of 74 μM compared to the wild type parasite. This explained the specific binding of GA to LdHMGR enzyme. There was ∼2 fold depletion in ergosterol levels in wild type promastigotes compared to the HMGR overexpressors. This data was further validated by exogenous supplementation of GA treated cells with ergosterol and 40% reversal of growth inhibition was observed. The results obtained suggested that GA kills the parasite by affecting sterol biosynthetic pathway, especially by inhibiting the L. donovani HMGR and altering ergosterol levels. The finding from the current study shows that GA is a potential antileishmanial chemotherapeutic agent. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

    Science.gov (United States)

    Torella, M; Del Deo, F; Grimaldi, A; Iervolino, S A; Pezzella, M; Tammaro, C; Gallo, P; Rappa, C; De Franciscis, P; Colacurci, N

    2016-12-01

    To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if

  4. Total DNA of Glycyrrhiza uralensis transformed into Hansenula anomala by ion implantation:Preparing Glycyrrhizic acid in recombined yeasts

    International Nuclear Information System (INIS)

    Jin Xiang; Mao Peihong; Lu Jie; Ma Yuan

    2010-01-01

    Glycyrrhizic acid (GA) in Glycyrrhiza uralensis (G. uralensis) is physiologically active. In this study, the total DNA of wild G. uralensis was randomly transformed into Hansenula anomaly by implantation of low-energy Ar + and N + , to produce five recombinant yeast strains relating to biological synthesis of the GA or Glycyrrhetinic acid (GAs). After culturing in liquid medium for 96 h, the resultant GA, 18α-GAs and 18β-Gas were determined by reversed-phase high performance liquid chromatography (RP-HPLC), and the corresponding concentrations were 114.49, 0.56, and 0.81 mg·L -1 . After one hundred primers were analyzed with random amplified polymorphic DNA (RAPD), the seven different DNA fragments were produced by the N7059 strain of recombined yeasts, and, the polymerase chain reaction (PCR) verified that one of them came from the genome of G. uralensis, indicating a successful transfer of genetic information by ion implantation. (authors)

  5. Glucose and lipid metabolism in rats supplemented with glycyrrhizic acid exposed to short- or long- term stress and fed on a high-calorie diet

    OpenAIRE

    Yaw, Hui Ping

    2017-01-01

    Stress and consumption of high-calorie diet are well-recognized as the primary contributor to various metabolic diseases such as the metabolic syndrome. Glycyrrhizic acid (GA), an active compound in the root extract of the licorice plant, Glycyrrhiza glabra has been shown to improve hyperglycaemia and dyslipidaemia in rats fed on a high- calorie diet. However, the effect of GA on glucose and lipid metabolism in rats under stress in combination with high- calorie diet has yet to be expl...

  6. Glabridin and glycyrrhizic acid show no beneficial effect on the chemical composition and mechanical properties of bones in ovariectomized rats, when administered in moderate dose.

    Science.gov (United States)

    Kaczmarczyk-Sedlak, Ilona; Klasik-Ciszewska, Sylwia; Wojnar, Weronika

    2016-10-01

    One of the major causes of osteoporosis and bone fracture in postmenopausal women is estrogen deficiency. To prevent the fractures, and avoid the side effects of hormone replacement therapy, phytoestrogens including the isoflavonoids are used. In the presented study two constituents occurring in the licorice root-the isoflavane glabridin and triterpenoid saponin glycyrrhizic acid were examined on the skeletal system of ovariectomized rats. The female Wistar rats were divided into five groups: control group, ovariectomized group as well as three ovariectomized groups treated with estradiol (0.2mg/kg), glabridin (5mg/kg) or glycyrrhizic acid (15mg/kg). All substances were administered orally for 4 weeks. The estradiol served as a positive control. The mechanical properties of femoral diaphysis, tibial metaphysis and femoral neck were assessed using bending and compression tests. Moreover the chemical composition of the femur, tibia and L-4 vertebra - content of water, organic substances and minerals - was determined. Ovariectomy induced unfavorable changes in the skeletal system of the rats. Administration of glabridin and glycyrrhizic acid to the ovariectomized rats did not improve analyzed parameters of the bones. Obtained results indicate, that the tested substances revealed no beneficial effect on the mechanical properties and chemical composition of the tested bones, thus they cannot be used as the osteoporosis protective agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. 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.

  8. Electrochemical activity of iron in acid treated bentonite and influence of added nickel

    Energy Technology Data Exchange (ETDEWEB)

    Mudrinić, T., E-mail: tihana@nanosys.ihtm.bg.ac.rs [University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Center for Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Mojović, Z.; Milutinović-Nikolić, A. [University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Center for Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Mojović, M. [University of Belgrade, Faculty of Physical Chemistry, Studenski trg 12-16, 11000 Belgrade (Serbia); Žunić, M. [University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Center for Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Vukelić, N. [University of Belgrade, Faculty of Physical Chemistry, Studenski trg 12-16, 11000 Belgrade (Serbia); Jovanović, D. [University of Belgrade-Institute of Chemistry, Technology and Metallurgy, Center for Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia)

    2015-10-30

    Highlights: • Mild acid treatment followed by incorporation of nickel was performed on bentonite. • Modified bentonites based electrodes were tested in H{sub 2}SO{sub 4} by cyclic voltammetry. • Acid treatment increased current response of electroactive iron within smectite. • Incorporation of Ni improved reversibility of Fe{sup 2+}/Fe{sup 3+} oxidation/reduction process. - Abstract: Bentonite originated from Mečji Do, Serbia, was submitted to acid treatment at 70 °C for 30 min, while only the concentration of applied HCl varied. The obtained acid treated samples were used to modify glassy carbon (GC) electrode. The effect of applied acid treatment on the electrochemical behavior of GC electrodes modified with these materials was investigated. Furthermore, the effect of the introduction of nickel into acid treated samples was studied. The incorporation of nickel into acid treated bentonite was achieved by either ion exchange or impregnation/decomposition method. The obtained samples were characterized using the following methods: inductively coupled plasma (ICP), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and electron spin resonance (ESR) spectroscopy. The electrochemical behavior of these samples was tested by cyclic voltammetry in 0.1 mol dm{sup −3} H{sub 2}SO{sub 4} solution. The ICP, FTIR and ESR results exhibited a slight decrease of iron content in the acid treated samples. XRD and FTIR results confirmed that the conditions applied for the acid treatment were mild enough for the smectite structure to be preserved. The electrocatalytic test showed that the current response of Fe{sup 2+}/Fe{sup 3+} oxidation/reduction process increased on the GC electrodes separately modified with each of the acid treated samples in comparison with current obtained on the GC electrode modified with untreated sample. These results indicated that applied acid treatment probably increased the accessibility of the electroactive iron within

  9. 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.

  10. Incorporation of the Time-Varying Postprandial Increase in Splanchnic Blood Flow into a PBPK Model to Predict the Effect of Food on the Pharmacokinetics of Orally Administered High-Extraction Drugs.

    Science.gov (United States)

    Rose, Rachel H; Turner, David B; Neuhoff, Sibylle; Jamei, Masoud

    2017-07-01

    Following a meal, a transient increase in splanchnic blood flow occurs that can result in increased exposure to orally administered high-extraction drugs. Typically, physiologically based pharmacokinetic (PBPK) models have incorporated this increase in blood flow as a time-invariant fed/fasted ratio, but this approach is unable to explain the extent of increased drug exposure. A model for the time-varying increase in splanchnic blood flow following a moderate- to high-calorie meal (TV-Q Splanch ) was developed to describe the observed data for healthy individuals. This was integrated within a PBPK model and used to predict the contribution of increased splanchnic blood flow to the observed food effect for two orally administered high-extraction drugs, propranolol and ibrutinib. The model predicted geometric mean fed/fasted AUC and C max ratios of 1.24 and 1.29 for propranolol, which were within the range of published values (within 1.0-1.8-fold of values from eight clinical studies). For ibrutinib, the predicted geometric mean fed/fasted AUC and C max ratios were 2.0 and 1.84, respectively, which was within 1.1-fold of the reported fed/fasted AUC ratio but underestimated the reported C max ratio by up to 1.9-fold. For both drugs, the interindividual variability in fed/fasted AUC and C max ratios was underpredicted. This suggests that the postprandial change in splanchnic blood flow is a major mechanism of the food effect for propranolol and ibrutinib but is insufficient to fully explain the observations. The proposed model is anticipated to improve the prediction of food effect for high-extraction drugs, but should be considered with other mechanisms.

  11. Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

    Science.gov (United States)

    Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

    2013-01-01

    Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

  12. 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.

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

    Science.gov (United States)

    Refahi, Soheila; Pourissa, Masoud; Zirak, Mohammad Reza; Hadadi, GholamHassan

    2015-01-01

    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.

  14. Uncaria rhynchophylla (miq) Jack plays a role in neuronal protection in kainic acid-treated rats.

    Science.gov (United States)

    Tang, Nou-Ying; Liu, Chung-Hsiang; Su, Shan-Yu; Jan, Ya-Min; Hsieh, Ching-Tou; Cheng, Chin-Yi; Shyu, Woei-Cherng; Hsieh, Ching-Liang

    2010-01-01

    Uncaria rhynchophylla (Miq) Jack (UR) is one of many Chinese herbs. Our previous studies have shown that UR has both anticonvulsive and free radical-scavenging activities in kainic acid (KA)-treated rats. The aim of the present study was to use the effect of UR on activated microglia, nitric oxide synthase, and apoptotic cells to investigate its function in neuroproction in KA-treated rats. UR of 1.0 or 0.5 g/kg was orally administered for 3 days (first day, second day, and 30 min prior to KA administration on the third day), or 10 mg/kg (intraperitoneal injection, i.p.) N-nitro-L-arginine methyl ester (L-NAME) 30 min prior to KA (2 microg/2 microl) was injected into the right hippocampus region of Sprague-Dawly rats. ED1 (mouse anti rat CD68), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) immunoreactive cells and apoptotic cells were observed in the hippocampus region. The results indicated that 1.0 g/kg, 0.5 g/kg of UR and 10 mg/kg of L-NAME reduced the counts of ED1, nNOS, iNOS immunoreactive cells and apoptotic cells in KA-treated rats. This study demonstrates that UR can reduce microglia activation, nNOS, iNOS and apoptosis, suggesting that UR plays a neuro-protective role against neuronal damage in KA-treated rats.

  15. Efficacy of orally administered prednisolone versus partial endodontic treatment on pain reduction in emergency care of acute irreversible pulpitis of mandibular molars: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Kérourédan, Olivia; Jallon, Léonard; Perez, Paul; Germain, Christine; Péli, Jean-François; Oriez, Dominique; Fricain, Jean-Christophe; Arrivé, Elise; Devillard, Raphaël

    2017-03-28

    Irreversible pulpitis is a highly painful inflammatory condition of the dental pulp which represents a common dental emergency. Recommended care is partial endodontic treatment. The dental literature reports major difficulties in achieving adequate analgesia to perform this emergency treatment, especially in the case of mandibular molars. In current practice, short-course, orally administered corticotherapy is used for the management of oral pain of inflammatory origin. The efficacy of intraosseous local steroid injections for irreversible pulpitis in mandibular molars has already been demonstrated but resulted in local comorbidities. Oral administration of short-course prednisolone is simple and safe but its efficacy to manage pain caused by irreversible pulpitis has not yet been demonstrated. This trial aims to evaluate the noninferiority of short-course, orally administered corticotherapy versus partial endodontic treatment for the emergency care of irreversible pulpitis in mandibular molars. This study is a noninferiority, open-label, randomized controlled clinical trial conducted at the Bordeaux University Hospital. One hundred and twenty subjects will be randomized in two 1:1 parallel arms: the intervention arm will receive one oral dose of prednisolone (1 mg/kg) during the emergency visit, followed by one morning dose each day for 3 days and the reference arm will receive partial endodontic treatment. Both groups will receive planned complete endodontic treatment 72 h after enrollment. The primary outcome is the proportion of patients with pain intensity below 5 on a Numeric Scale 24 h after the emergency visit. Secondary outcomes include comfort during care, the number of injected anesthetic cartridges when performing complete endodontic treatment, the number of antalgic drugs and the number of patients coming back for consultation after 72 h. This randomized trial will assess the ability of short-term corticotherapy to reduce pain in irreversible

  16. Immunomodulatory effects of orally administered aqueous extract ...

    African Journals Online (AJOL)

    This paper reported the immunnodulation tests of Eupolyphaga sinensis Walker in immunity. Mice were fed with E. sinensis water-decoction at a dose of 1.89, 3.78 and 7.56 g/kg/d for 4 weeks, then their immune function was studied. The results of the effects of E. sinensis water-decoction on spleen index, thymus index and ...

  17. 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

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

    KAUST Repository

    Sarath Kumar, S. R.; Kurra, Narendra; Alshareef, Husam N.

    2015-01-01

    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.

  19. 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.

  20. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Science.gov (United States)

    Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

    2016-01-01

    The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

  1. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

    Directory of Open Access Journals (Sweden)

    Pirow Bekker

    Full Text Available The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan, an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

    NARCIS (Netherlands)

    Brouwers, J.E.M.; Ruchselman, M.; Rietbergen, van B.; Bouxsein, M.L.

    2009-01-01

    Summary Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other

  4. Reduction of As(V) to As(III) by commercial ZVI or As(0) with acid-treated ZVI

    International Nuclear Information System (INIS)

    Sun, Fenglong; Osseo-Asare, Kwadwo A.; Chen, Yongsheng; Dempsey, Brian A.

    2011-01-01

    Graphical abstract: Acid-treated ZVI (right) reduced As(V) to the less toxic As(0) while commercial ZVI reduced As(V) to As(III). There was no lag phase in either reaction when rigorously anoxic conditions were maintained. Highlights: ► Acid-treated ZVI reduced As(V) to the less toxic As(0). ► Commercial ZVI reduced As(V) to As(III), which was not released to solution. ► Magnetite/Fe(II) did not reduce As(V) even though the reaction is thermodynamically spontaneous. ► No lag phase was observed in any of the reactions, contrary to prior reports. ► Rigorously anoxic conditions seem necessary for observing these reactions. - Abstract: Zero-valent iron (ZVI) consists of an elemental iron core surrounded by a shell of corrosion products, especially magnetite. ZVI is used for in situ removal or immobilization of a variety of contaminants but the mechanisms for removal of arsenic remain controversial and the mobility of arsenic after reaction with ZVI is uncertain. These issues were addressed by separately studying reactions of As(V) with magnetite, commercial ZVI, and acid-treated ZVI. Strictly anoxic conditions were used. Adsorption of As(V) on magnetite was fast with pH dependence similar to previous reports using oxic conditions. As(V) was not reduced by magnetite and Fe(II) although the reaction is thermodynamically spontaneous. As(V) reactions with ZVI were also fast and no lag phase was observed which was contrary to previous reports. Commercial ZVI reduced As(V) to As(III) only when As(V) was adsorbed, i.e., for pH < 7. As(III) was not released to solution. Acid-treated ZVI reduced As(V) to As(0), shown using wet chemical analyses and XANES/EXAFS. Comparisons were drawn between reactivity of acid-treated ZVI and nano-ZVI; if true then acid-treated ZVI could provide similar reactive benefits at lower cost.

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

    International Nuclear Information System (INIS)

    Wang, D.; Guo, T.Q.; Wang, Z.Y.; Lu, J.H.; Liu, D.P.; Meng, Q.F.; Xie, J.; Zhang, X.L.; Liu, Y.; Teng, L.S.

    2014-01-01

    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

  6. 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.

  7. Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF-κB.

    Science.gov (United States)

    Mao, Yulong; Wang, Baikui; Xu, Xin; Du, Wei; Li, Weifen; Wang, Youming

    2015-01-01

    The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.

  8. 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.

  9. Anti-Inflammatory Activities of Licorice Extract and Its Active Compounds, Glycyrrhizic Acid, Liquiritin and Liquiritigenin, in BV2 Cells and Mice Liver

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Yu

    2015-07-01

    Full Text Available This study provides the scientific basis for the anti-inflammatory effects of licorice extract in a t-BHP (tert-butyl hydrogen peroxide-induced liver damage model and the effects of its ingredients, glycyrrhizic acid (GA, liquiritin (LQ and liquiritigenin (LG, in a lipopolysaccharide (LPS-stimulated microglial cell model. The GA, LQ and LG inhibited the LPS-stimulated elevation of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, tumor necrosis factor (TNF-alpha, interleukin (IL-1beta and interleukin (IL-6 in BV2 (mouse brain microglia cells. Furthermore, licorice extract inhibited the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6 in the livers of t-BHP-treated mice models. This result suggested that mechanistic-based evidence substantiating the traditional claims of licorice extract and its three bioactive components can be applied for the treatment of inflammation-related disorders, such as oxidative liver damage and inflammation diseases.

  10. Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease.

    Science.gov (United States)

    Wang, Jingjing; Chen, Xiaoqing; Wang, Wei; Zhang, Yating; Yang, Ziying; Jin, Yu; Ge, Hui Ming; Li, Erguang; Yang, Guang

    2013-05-02

    The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in China. Glycyrrhizic acid (GA) is considered the principal component in Glycyrrhiza spp. with a wide spectrum of antiviral activity. The present study attempt to validate the medicinal use of Glycyrrhiza uralensis for hand, foot and mouth disease (HFMD) and further to verify whether GA is an active antiviral component in the water extract of Glycyrrhiza uralensis. Radices of Glycyrrhiza uralensis Fisch. were extracted with hot water. The chemical contents of the extract were profiled with HPLC analysis. The antiviral activity of the extract and the major components was evaluated against infection of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) on Vero cells. The cytopathic effect caused by the infection was measured with MTT assay. Infectious virion production was determined using secondary infection assays and viral protein expression by immunoblotting analysis. The extract at 1000 μg/ml suppressed EV71 replication by 1.0 log and CVA16 by 1.5 logs. The antiviral activity was associated with the content of GA in the extract since selective depletion of GA from the extract by acid precipitation resulted in loss of antiviral activity. In contrast, the acid precipitant retained antiviral activity. The precipitant at a concentration of 200 μg/ml inhibited EV71 and CVA16 replication by 1.7 and 2.2 logs, respectively. Furthermore, GA dose-dependently blocked viral replication of EV71 and CVA16. At 3 mM, GA reduced infectious CVA16 and EV71 production by 3.5 and 2.2 logs, respectively. At 5mM, CVA16 production was reduced by 6.0 logs and EV71 by 4.0 logs. Both EV71 and CVA16 are members of Enterovirus genus, time-of-drug addition studies however showed that GA directly inactivated CVA16, while GA anti-EV71 effect

  11. 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 ...

  12. Insecticidal Potential of an Orally Administered Metabolic Extract of ...

    African Journals Online (AJOL)

    The insecticidal activity of Aspergillus niger IHCS-4 metabolic extract against Chrysomya chloropyga larvae was examined in vitro. The toxicity test revealed that 0.04 mg/g and 0.08 mg/g extract concentration significantly (P>0.05) affected the insect larvae, inducing 20% and 65% mortality respectively, within 24 hours.

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

    African Journals Online (AJOL)

    Objectives. This study assessed the efficacy of the two outpatient processes of single-dose 50 μg oral misoprostol (OM) and membrane sweeping (MS) on the outcome of labour induction and the possibility of reducing the need for hospital admission for cervical ripening/labour induction in uncomplicated post-term singleton ...

  14. Absorption of orally administered 65Zn by normal human subjects

    International Nuclear Information System (INIS)

    Aamodt, R.L.; Rumble, W.F.; Johnston, G.S.; Markley, E.J.; Henkin, R.I.

    1981-01-01

    Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption

  15. 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.

  16. 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.

  17. 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

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

    African Journals Online (AJOL)

    produce clinically important benefits;11 however, it may be beneficial ... membrane sweeping for labour induction in uncomplicated ... Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology Teaching Hospital, ...

  19. Transfer of Orally Administered Terpenes in Goat Milk and Cheese

    Directory of Open Access Journals (Sweden)

    I. Poulopoulou

    2012-10-01

    Full Text Available The objective of the present study was to investigate the relationships between terpenes’ intake and their presence in animal tissues (blood and milk as well as in the final product (cheese. Eight dairy goats were divided in two balanced groups, representing control (C and treatment (T group. In T group oral administration of a mixture of terpenes (α-pinene, limonene and β-caryophyllene was applied over a period of 18 d. Cheese was produced, from C and T groups separately, on three time points, twice during the period of terpenes’ oral administration and once after the end of experiment. Terpenes were identified in blood by extraction using petroleum ether and in milk and cheese by the use of solid phase micro-extraction (SPME method, followed by GC-MS analysis. Chemical properties of the milk and the produced cheeses were analyzed and found not differing between the two groups. Limonene and α-pinene were found in all blood and milk samples of the T group after a lag-phase of 3 d, while β-caryophyllene was determined only in few milk samples. Moreover, none of the terpenes were traced in blood and milk of C animals. In cheese, terpenes’ concentrations presented a more complicated pattern implying that terpenes may not be reliable feed tracers. We concluded that monoterpenes can be regarded as potential feed tracers for authentification of goat milk, but further research is required on factors affecting their transfer.

  20. 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.

  1. Evaluation on the concentration change of paeoniflorin and glycyrrhizic acid in different formulations of Shaoyao-Gancao-Tang by the tri-level infrared macro-fingerprint spectroscopy and the whole analysis method

    Science.gov (United States)

    Liu, Aoxue; Wang, Jingjuan; Guo, Yizhen; Xiao, Yao; Wang, Yue; Sun, Suqin; Chen, Jianbo

    2018-03-01

    As a kind of common prescriptions, Shaoyao-Gancao-Tang (SGT) contains two Chinese herbs with four different proportions which have different clinical efficacy because of their various components. In order to investigate the herb-herb interaction mechanisms, we used the method of tri-level infrared macro-fingerprint spectroscopy to evaluate the concentration change of active components of four SGTs in this research. Fourier transform infrared spectroscopy (FT-IR) and Second derivative infrared spectroscopy (SD-IR) can recognize the multiple prescriptions directly and simultaneously. 2D-IR spectra enhance the spectral resolution and obtain much new information for discriminating the similar complicated samples of SGT. Furthermore, the whole analysis method from the analysis of the main components to the specific components and the relative content of the components may evaluate the quality of TCM better. Then we concluded that paeoniflorin and glycyrrhizic acid were the highest proportion in active ingredients in SGT-12:1 and the lowest one in SGT-12:12, which matched the HPLC-DAD results. It is demonstrated that the method composed by the tri-level infrared macro-fingerprint spectroscopy and the whole analysis can be applicable for effective, visual and accurate analysis and identification of very complicated and similar mixture systems of traditional Chinese medicine.

  2. 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.

  3. 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.

  4. Electrochemical corrosion behavior of acid treated strip cast AM50 and AZX310 magnesium alloys in 3.5 wt.% NaCl solution

    Directory of Open Access Journals (Sweden)

    Srinivasan Arthanari

    2017-09-01

    Full Text Available The influence of acid treatments on the surface morphology and electrochemical corrosion behavior of strip-cast AM50 and AZX310 alloys have been studied in the present investigation. The alloys were acid treated using H3PO4 (AT-1, HF (AT-2 and HNO3 (AT-3 for different treatment durations viz., 60, 300 and 600 s. The acid treatments produced a surface layer consisting of corresponding magnesium salts of the acids and were confirmed from the X-ray diffraction (XRD, scanning electron microscopy (SEM and energy dispersive X-ray analysis (EDAX. AT-1 treatment produced cracked and network porous morphology for AM50 and AZX310 alloys respectively and AT-3 treatment exhibited dense creaked surface layer formation while AT-2 does not produce any significant change in the morphology. Polarization studies revealed that, the acid treatment significantly altered the corrosion process by altering anodic and cathodic reaction rates of AM50 and AZX310 alloys. The HNO3 (AT-3 treatment was effective compared to other treatments to control the corrosion rate in the studied treatment conditions. The surface morphology and chemical composition of surface layer produced during the treatment was correlated to explain the corrosion results.

  5. Characterization of absorption enhancers for orally administered therapeutic peptides in tablet formulations - Applying statistical learning

    DEFF Research Database (Denmark)

    Welling, Søren Havelund

    . In the Caco-2 model all reagents are pre-dissolved, and therefore the assay cannot predict critical solubility issues and bile salt interactions in the final tablet formulation. A QSAR solubility model was built to foresee and avoid slow tablet dissolution. Due to enzyme kinetics, slow tablet dissolution...

  6. Antimalarial Activity of Orally Administered Curcumin Incorporated in Eudragit®-Containing Liposomes

    Directory of Open Access Journals (Sweden)

    Elisabet Martí Coma-Cros

    2018-05-01

    Full Text Available Curcumin is an antimalarial compound easy to obtain and inexpensive, having shown little toxicity across a diverse population. However, the clinical use of this interesting polyphenol has been hampered by its poor oral absorption, extremely low aqueous solubility and rapid metabolism. In this study, we have used the anionic copolymer Eudragit® S100 to assemble liposomes incorporating curcumin and containing either hyaluronan (Eudragit-hyaluronan liposomes or the water-soluble dextrin Nutriose® FM06 (Eudragit-nutriosomes. Upon oral administration of the rehydrated freeze-dried nanosystems administered at 25/75 mg curcumin·kg−1·day−1, only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.

  7. Lipopolysaccharide contamination of beta-lactoglobulin affects the immune response against intraperitoneally and orally administered antigen

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Kjær, T.M.R.; Barkholt, Vibeke

    2004-01-01

    Microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram- negative bacteria, is extensively present in food products like co......-LG was contaminated with LPS. Conclusions: LPS contamination of an aqueous protein solution does not affect oral tolerance induction, whereas LPS present in emulsion prevents oral tolerance induction towards the food protein.......Microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram- negative bacteria, is extensively present in food products like cow......'s milk. It is not well established, however, how this presence of LPS affects oral tolerance induction. Methods: We studied the effect of LPS contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen-specific immune responses. IgG1/IgG2a production upon...

  8. 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

    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...... penetration for a significant number of marketed central nervous system (CNS) agents. The Biopharmaceutics Drug Disposition Classification System (BDDCS) has proved useful in predicting drug disposition in the human body, particularly in the liver and intestine. Here we discuss the value of using BDDCS...

  9. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

    Science.gov (United States)

    Kim, Y I; Fluckiger, L; Hoffman, M; Lartaud-Idjouadiene, I; Atkinson, J; Maincent, P

    1997-02-01

    1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

  10. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    Fauran-Clavel, M.J.; Oustrin, J.; Godin, J.; Boudene, C.

    1982-01-01

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m 3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd ++ ion on the bone crystallization process [fr

  11. Effect of orally administered sodium bicarbonate on caecal pH.

    Science.gov (United States)

    Taylor, E A; Beard, W L; Douthit, T; Pohlman, L

    2014-03-01

    Caecal acidosis is a central event in the metabolic cascade that occurs following grain overload. Buffering the caecal acidosis by enterally administered sodium bicarbonate (NaHCO3 ) may be beneficial to affected horses. To determine the effect and duration of enterally administered NaHCO3 on caecal pH in healthy horses. Experimental study using horses with caecal cannulas. Nine horses had been previously fitted with a caecal cannula. Six horses received 1.0 g/kg bwt NaHCO3 and 3 control horses were given 3 l of water via nasogastric tube. Clinical parameters, water consumption, venous blood gases, caecal pH, faecal pH and faecal water content were measured at 6 h intervals over a 36 h study period. Horses that received enterally administered NaHCO3 had significantly increased caecal pH that lasted the duration of the study. Treated horses increased their water intake, and developed metabolic alkalaemia, significantly increased plasma sodium concentrations and significantly decreased plasma potassium concentrations. Enterally administered NaHCO3 may be beneficial in buffering caecal acidosis. © 2013 EVJ Ltd.

  12. Orally administered Chrysin improves post-thawed sperm quality and fertility of rooster.

    Science.gov (United States)

    Zhandi, M; Ansari, M; Roknabadi, P; Zare Shahneh, A; Sharafi, M

    2017-12-01

    Chrysin is a bioflavonoid compound found in passion flower, chamomile, propolis and honey at high levels. Post-thawed sperm quality and fertility of Chrysin-fed roosters were assessed in this study. Twenty 40-week-old male broiler breeders were randomly divided into four groups and fed basal diet supplemented with different levels of Chrysin including 0 (Ch-0), 25 (Ch-25), 50 (Ch-50) or 75 (Ch-75) mg/day for 12 consecutive weeks. Semen samples were weekly collected from 6th to 9th week of experiment to evaluate some sperm quality parameters including total and progressive motility, plasma membrane integrity and functionality (in fresh and post-thawed samples) and mitochondrial activity (only in post-thawed samples). Also, collected semen samples from 10th, 11th and 12th week of experiment were frozen and then artificially inseminated to test fertility rate. According to the results, an improvement in both fresh and post-thawed sperm quality including total [fresh: 88.00 ± 0.58 and 87.25 ± 0.67 (p roosters could ameliorate cryopreservation-induced impairment of sperm quality and fertility rate. © 2017 Blackwell Verlag GmbH.

  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

  14. Growth phase of orally administered Lactobacillus strains differentially affects T helper-cell pathways

    NARCIS (Netherlands)

    Maassen, C.B.M.; Boersma, W.J.A.; Holten-Neelen, van J.C.P.A.; Claassen, E.A.W.; Laman, J.D.

    2003-01-01

    Lactobacillus strains with probiotic activity are major constituents of numerous common food products. Due to their `generally regarded as safe¿-status (GRAS-status), Lactobacillus strains can also be genetically engineered for use in oral immunotherapeutic applications, such as vaccination and T

  15. Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model.

    Science.gov (United States)

    Li, Wenyang; Zhu, Songsong; Hu, Jing

    2015-07-01

    Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus. We asked whether bovine lactoferrin enhances bone formation of the distraction callus as determined by (1) radiographic and histologic appearances; (2) dual-energy x-ray absorptiometry (DXA) analysis of bone mineral composition and bone mineral density; (3) micro-CT measures of trabecular architecture; and (4) biomechanical strength of the healing bone. Additionally, serology, reverse transcription (RT)-PCR, and immunohistochemistry were used to explore the possible mechanisms of bovine lactoferrin use on bone formation during distraction osteogenesis. Unilateral tibial osteodistraction was performed on 80 New Zealand White rabbits with a distraction rate of 1 mm per day for 10 days. Animals then were divided randomly into two groups: (1) vehicle and (2) bovine lactoferrin. At 4 and 8 weeks after completion of distraction, the animals were sacrificed. Lengthened tibias and serum samples were obtained and subjected to radiologic, DXA, micro-CT, histologic, and biomechanical examinations, and serum, RT-PCR and immunohistochemical analyses. Radiologic, DXA, micro-CT, histologic, and biomechanical examinations indicated that bovine lactoferrin treatment not only accelerated bone formation at early stages of distraction osteogenesis but also promoted bone consolidation at late stages. The ultimate force of the distracted calluses was increased by 37% (118.8 ± 6.65 N in the lactoferrin group and 86.5 ± 5.47 N in the vehicle group; p bovine lactoferrin treatment significantly increased serum levels of bone alkaline phosphatase and decreased serum levels of tartrate resistant acid phosphatase 5b. In addition, RT-PCR and immunohistochemical analyses suggested that bovine lactoferrin treatment induced a lower receptor activator of nuclear factor-kappaB (RANK) ligand/osteoprotegerin (RANKL/OPG) ratio in the distracted callus. The results of our study suggest that bovine lactoferrin treatment could promote bone regeneration during distraction osteogenesis in the rabbit. The results indicate that the OPG/RANKL/RANK system might be a major mechanism for increased bone formation and decreased bone resorption in distraction osteogenesis with bovine lactoferrin treatment. Oral administration of bovine lactoferrin may provide a feasible approach for promoting osteogenesis during distraction osteogenesis.

  16. 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.

  17. Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.

    Science.gov (United States)

    Saarikoski, Tuukka; Saari, Teijo I; Hagelberg, Nora M; Backman, Janne T; Neuvonen, Pertti J; Scheinin, Mika; Olkkola, Klaus T; Laine, Kari

    2015-03-01

    Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor). We used a randomized placebo-controlled crossover study design with 12 healthy subjects, of which 8 were extensive and 4 were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine (250 mg once daily), itraconazole (200 mg once daily) or placebo, subjects were given tramadol 50 mg orally. Plasma concentrations of tramadol and M1 were determined over 48 h and some pharmacodynamic effects over 12 h. Pharmacokinetic variables were calculated using standard non-compartmental methods. Terbinafine increased the area under plasma concentration-time curve (AUC0-∞) of tramadol by 115 % and decreased the AUC0-∞ of M1 by 64 % (P Terbinafine increased the peak concentration (C max) of tramadol by 53 % (P terbinafine pretreatment the elimination half-life of tramadol and M1 were increased by 48 and 50 %, respectively (P Terbinafine reduced subjective drug effect of tramadol (P Terbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.

  18. Measurement of the incorporation of orally administered arachidonic acid into tissue lipids

    International Nuclear Information System (INIS)

    Kulmacz, R.J.; Sivarajan, M.; Lands, W.E.

    1986-01-01

    The applicability of a stable isotope method to monitor the mixing of dietary arachidonic acid with endogenous arachidonic acid in tissue lipids was evaluated. Rats were fed octadeuterated arachidonic acid during a 20-day period, and the entry of the dietary acid into lipid esters of various tissues was examined by gas chromatography-mass spectrometric (GC-MS) analysis of their fatty acids. The rats were maintained on a fat-free diet from weaning until 63 days old to enhance the ratio of the dietary acid to endogenous arachidonate. Three separate forms of eicosatetraenoic acid in the tissue lipids could be distinguished by GC-MS: octadeuterated arachidonic acid (recent dietary origin), unlabeled arachidonic acid (maternal origin) and unlabeled 4,7,10,13-eicosatetraenoic acid (originating from palmitoleic acid). The total eicosatetraenoic acid in the tissue lipids contained about 90% arachidonate from recent dietary origin in lung, kidney, heart and fat, 70% in muscle and liver and 27% in brain. The n-7 isomer of eicosatetraenoic acid was estimated to make up 6% or less of the total eicosatetraenoic acid in lung, kidney, brain, muscle and heart tissue lipids, but it comprised around 15% of the total eicosatetraenoic acid in liver. The unlabeled arachidonic acid of maternal origin thus comprised only about 10% of the eicosatetraenoic acid in all tissues examined except muscle and brain, where it was 24% and 70% of the eicosatetraenoic acid, respectively

  19. Calming effect of orally administered γ-aminobutyric acid in Shih Tzu dogs.

    Science.gov (United States)

    Uetake, Katsuji; Okumoto, Ayano; Tani, Noriko; Goto, Akihiro; Tanaka, Toshio

    2012-12-01

    The calming effects of γ-aminobutyric acid (GABA) by oral administration were investigated in four adult Shih Tzu dogs. Three dosage levels (1, 2 and 4 mg/kg body weight) and non-administration were tested by an increase and decrease method. Changes in activity (for 1.5 h) and urinary cortisol levels (pre-administration, 3 and 7 h later) of dogs were monitored after administration. Without reference to dosage level, the mean times spent standing (P = 0.06), sitting (P level was observed at 7 h after administration (P GABA exerts calming effects on dogs as well as humans. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

  20. An overview of site-specific delivery of orally administered proteins ...

    African Journals Online (AJOL)

    Oral delivery of proteins and peptides poses one of the greatest challenges in controlled drug delivery due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. Therapeutic proteins/peptides are useful in correcting metabolic disorders (e.g., insulin in diabetes mellitus), ...

  1. Health benefits of orally administered anti-IL-10 antibody in milk-fed dairy calves.

    Science.gov (United States)

    Raabis, S M; Ollivett, T L; Cook, M E; Sand, J M; McGuirk, S M

    2018-05-16

    The primary objective of this randomized controlled trial was to determine whether anti-IL-10 egg yolk antibodies fed upon arrival to a calf ranch would lower the prevalence of Cryptosporidium parvum shedding in naturally challenged preweaned dairy calves. The secondary objectives included measuring the effect of anti-IL-10 antibodies on calf health, performance, and shedding of less common diarrheal pathogens. A total of 133 calves, enrolled at 24 to 72 h of age, received a daily dose of 0.96 g of egg yolk powder with anti-IL-10 antibodies (MAB, n = 71) or without anti-IL-10 antibodies (MEP, n = 62) split between 2 feedings for the first 11 d on feed at a calf ranch. Daily health evaluations were completed for 15 d after arrival and on d 56. Digital weights were collected at enrollment and d 56, and hipometer weights were collected at enrollment and d 7 and 56. Packed cell volume and serum total protein concentration were measured at enrollment and on d 7 and 14. Fecal pH was measured at enrollment and on d 5 and 14, and fecal pathogen (C. parvum, coronavirus, rotavirus, and Salmonella spp.) shedding was assessed at d 5 and 14. Continuous outcomes were compared between groups using a Student's t-test or Wilcoxon rank sum test. Fecal pathogen shedding at d 14, respiratory disease at d 56, and antibiotic usage were compared using relative risk (RR) and chi-squared test. Fecal pH (median and interquartile range) on d 14 was 6.65 (6.39-6.99) and 6.52 (5.97-6.81) for MAB and MEP, respectively. On d 56, the risk of respiratory disease was lower for MAB compared with MEP (RR = 0.40; confidence interval = 0.16-0.99). The risk for antibiotic treatment was lower for MAB- compared with MEP-treated calves (RR = 0.38; confidence interval = 0.17-0.88). The risk of shedding rotavirus was higher in MAB (RR = 1.38; confidence interval = 1.10-1.81) calves. After multivariable analyses, hipometer weights (least squares means ± standard error) were 1.7 ± 0.8 kg greater on d 56 in MAB compared with MEP; however, ADG was 0.04 ± 0.02 kg/d lower in MAB calves. Total health score, diarrhea days, average respiratory score, packed cell volume, and serum total protein were not affected by feeding anti-IL-10 egg antibodies. In summary, feeding anti-IL-10 antibodies was associated with increased fecal pH, reduced risk of respiratory disease later in the preweaning period, and decreased antibiotic usage despite higher rotavirus infection. These findings might be associated with improved mucosal immunity, enhanced host defenses, or reduced susceptibility and warrant further investigation. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

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

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available 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.

  4. Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats

    Science.gov (United States)

    Nagahama, Kenji; Nishio, Hikaru; Yamato, Masanori; Takeuchi, Koji

    2012-01-01

    Summary Background Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats. Material/Methods After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor. Results The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action. Conclusions The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide. PMID:22207112

  5. 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.

  6. Alteration of intestinal microbiota in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Directory of Open Access Journals (Sweden)

    Krisana Asano

    Full Text Available Proteoglycan (PG extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community.

  7. Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

    Science.gov (United States)

    Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

    2017-04-03

    Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

  8. Distribution of orally administered and chronically fed sup(95m)Tc in Japanese quail tissues and eggs

    International Nuclear Information System (INIS)

    Thomas, J.M.; Cadwell, L.L.; Cataldo, D.A.; Garland, T.R.

    1986-01-01

    In the present study, male and female Japanese quail were chronically fed alfalfa grown on solutions containing TcO 4 which was mixed into a commercial turkey starter. The objective was to estimate concentration ratios and transfer coefficients from Tc incorporated into alfalfa tissue to quail eggs, edible tissues and other organs. (author)

  9. Development of a sedation protocol using orally administered tiletamine-zolazepam-acepromazine in free-roaming dogs.

    Science.gov (United States)

    Huang, Hsiao-Chun; Huang, Shih-Wei; Yu, Kuan-Hua; Wang, Jiann-Hsiung; Wu, Jui-Te

    2017-09-01

    To investigate the sedative effects in dogs of tiletamine-zolazepam-acepromazine (TZA) or ketamine-flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs. Experimental study followed by a field trial. Six research dogs and 27 free-roaming dogs. In a pilot study, six research dogs were administered liquid TZA (20 mg kg -1 tiletamine-zolazepam and 2 mg kg -1 acepromazine) or liquid KF (50 mg kg -1 ketamine and 2 mg kg -1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs. In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35-80) minutes (67%); treatment 2, 30 (15-65) minutes (83%); and treatment 3, 75 (45-110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg -1 ) and acepromazine (2 mg kg -1 ). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg -1 ) and xylazine (1.1-2.2 mg kg -1 ) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food. Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  10. Orally administered marine (1-3)-Beta-D-glucan Phycarine stimulates both humoral and cellular immunity

    Czech Academy of Sciences Publication Activity Database

    Větvička, V.; Dvořák, B.; Větvičková, J.; Richter, Jan; Křižan, Jiří; Šíma, Petr; Yvin, J.; C.

    2007-01-01

    Roč. 40, - (2007), s. 291-298 ISSN 0141-8130 R&D Projects: GA ČR GA301/05/0078 Institutional research plan: CEZ:AV0Z50200510 Keywords : phagocytosis * immunity * cancer Subject RIV: EE - Microbiology, Virology Impact factor: 1.578, year: 2007

  11. Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep.

    Science.gov (United States)

    Marini, D; Pippia, J; Colditz, I G; Hinch, G; Petherick, J C; Lee, C

    2015-08-01

    To determine the efficacy and bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep. Randomised experimental design with four treatment groups: three NSAID groups and one control group (n = 10/group). The study animals were 40 18-month-old Merino ewes with an average weight of 31.4 ± 0.5 kg. Treatment was given orally at 24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce inflammation and pain; responses (force plate pressure, skin temperature, limb circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12, 24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by ultra-high-pressure liquid chromatography. The NSAIDs were detectable in ovine plasma 2 h after oral administration, with average concentrations of 4.5-8.4 µg/mL for ketoprofen, 2.6-4.1 µg/mL for flunixin and 30-80 µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. Pain response to an oil of turpentine injection was assessed using the measures applied but no effect of the NSAIDs was observed. Although this pain model has been previously validated, the responses observed in this study differed from those in the previous study. The three NSAIDs reached inferred therapeutic concentrations in blood at 2 h after oral administration. The oil of turpentine lameness model may need further validation. © 2015 Australian Veterinary Association.

  12. Age-related P-glycoprotein expression in the intestine and affecting the pharmacokinetics of orally administered enrofloxacin in broilers.

    Science.gov (United States)

    Guo, Mengjie; Bughio, Shamsuddin; Sun, Yong; Zhang, Yu; Dong, Lingling; Dai, Xiaohua; Wang, Liping

    2013-01-01

    Bioavailability is the most important factor for the efficacy of any drug and it is determined by P- glycoprotein (P-gp) expression. Confirmation of P-gp expression during ontogeny is needed for understanding the differences in therapeutic efficacy of any drug in juvenile and adult animals. In this study, Abcb1 mRNA levels in the liver and intestine of broilers during ontogeny were analysed by RT qPCR. Cellular distribution of P-gp was detected by immunohistochemstry. Age-related differences of enrofloxacin pharmacokinetics were also studied. It was found that broilers aged 4 week-old expressed significantly (P0.05) age-related difference in the duodenum. Furthermore, the highest and lowest levels of Abcb1 mRNA expression were observed in the jejunum, and duodenum, respectively. P-gp immunoreactivity was detected on the apical surface of the enterocytes and in the bile canalicular membranes of the hepatocytes. Pharmacokinetic analysis revealed that the 8 week-old broilers, when orally administrated enrofloxacin, exhibited significantly higher Cmax (1.97 vs. 0.98 μg • ml(-1), P=0.009), AUC(14.54 vs. 9.35 μg • ml(-1) • h, P=0.005) and Ka (1.38 vs. 0.43 h(-1), P=0.032), as well as lower Tpeak (1.78 vs. 3.28 h, P=0.048) and T1/2 ka (0.6 vs. 1.64 h, P=0.012) than the 4 week-old broilers. The bioavailability of enrofloxacin in 8 week-old broilers was increased by 15.9%, compared with that in 4 week-old birds. Interestingly, combining verapamil, a P-gp modulator, significantly improved pharmacokinetic behaviour of enrofloxacin in all birds. The results indicate juvenile broilers had a higher expression of P-gp in the intestine, affecting the pharmacokinetics and reducing the bioavailability of oral enrofloxacin in broilers. On the basis of our results, it is recommended that alternative dose regimes are necessary for different ages of broilers for effective therapy.

  13. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial.

    Science.gov (United States)

    Avni, Isaac; Garzozi, Hanna J; Barequet, Irina S; Segev, Fanni; Varssano, David; Sartani, Gil; Chetrit, Noa; Bakshi, Erez; Zadok, David; Tomkins, Oren; Litvin, Gilad; Jacobson, Kenneth A; Fishman, Sari; Harpaz, Zivit; Farbstein, Motti; Yehuda, Sara Bar; Silverman, Michael H; Kerns, William D; Bristol, David R; Cohn, Ilan; Fishman, Pnina

    2010-07-01

    To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. Proprietary or commercial disclosure may be found after the references. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Enhanced bioavailability of orally administered flurbiprofen by combined use of hydroxypropyl-cyclodextrin and poly(alkyl-cyanoacrylate) nanoparticles.

    Science.gov (United States)

    Zhao, Xiaoyun; Li, Wei; Luo, Qiuhua; Zhang, Xiangrong

    2014-03-01

    Flurbiprofen was formulated into nanoparticle suspension to improve its oral bioavailability. Hydroxypropyl-β-cyclodextrin inclusion-flurbiprofen complex (HP-β-CD-FP) was prepared, then incorporating this complex into poly(alkyl-cyanoacrylate) (PACA) nanoparticles. HP-β-CD-FP-PACA nanoparticle was prepared by the emulsion solvent polymerization method. The zeta potential was -26.8 mV, the mean volume particle diameter was 134 nm, drug encapsulation efficiency was 53.3 ± 3.6 % and concentration was 1.5 mg/mL. The bioavailability of flurbiprofen from optimized nanoparticles was assessed in male Wistar rats at a dose of 15 mg/kg. As compared to the flurbiprofen suspension, 211.6 % relative bioavailability was observed for flurbiprofen nanoparticles. The reduced particle size and increased surface area may contribute to improve oral bioavailability of flurbiprofen.

  15. Orally administered Taenia solium Calreticulin prevents experimental intestinal inflammation and is associated with a type 2 immune response.

    Directory of Open Access Journals (Sweden)

    Fela Mendlovic

    Full Text Available Intestinal helminth antigens are inducers of type 2 responses and can elicit regulatory immune responses, resulting in dampened inflammation. Several platyhelminth proteins with anti-inflammatory activity have been reported. We have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT and shown that it predominantly induces a type 2 response characterized by IgG1, IL-4 and IL-5 production in mice. Here, we report the rTsCRT anti-inflammatory activity in a well-known experimental colitis murine model. Mice were orally immunized with purified rTsCRT and colitis was induced with trinitrobenzene sulfonic acid (TNBS. Clinical signs of disease, macroscopic and microscopic tissue inflammation, cytokine production and micronuclei formation, as a marker of genotoxicity, were measured in order to assess the effect of rTsCRT immunization on experimentally induced colitis. rTsCRT administration prior to TNBS instillation significantly reduced the inflammatory parameters, including the acute phase cytokines TNF-α, IL-1β and IL-6. Dampened inflammation was associated with increased local expression of IL-13 and systemic IL-10 and TGF-β production. Genotoxic damage produced by the inflammatory response was also precluded. Our results show that oral treatment with rTsCRT prevents excessive TNBS-induced inflammation in mice and suggest that rTsCRT has immunomodulatory properties associated with the expression of type 2 and regulatory cytokines commonly observed in other helminths.

  16. An orally administered lavandula oil preparation (Silexan) for anxiety disorder and related conditions: an evidence based review.

    Science.gov (United States)

    Kasper, Siegfried

    2013-11-01

    Silexan is a lavender oil preparation in gelatine capsules containing 80 mg. We reviewed the clinical trials investigating the anxiolytic efficacy and tolerability of Silexan as well as its safety and potential for drug interactions. Seven trials were included, among which four therapeutic trials had a treatment duration of 6 or 10 weeks. In patients with subsyndromal anxiety or generalised anxiety disorder (GAD) an anxiolytic effect of Silexan was evident after 2 weeks. Patients treated with Silexan showed Hamilton Anxiety Scale (HAMA) total score decreases between 10.4 ± 7.1 and 12.0 ± 7.2 points at Week 6 and between 11.8 ± 7.7 and 16.0 ± 8.3 points at Week 10. HAMA total score reductions between baseline and end of treatment were significantly superior to placebo in patients with subsyndromal anxiety and comparable to lorazepam in its starting dose in patients with GAD. Silexan had beneficial effects on typical co-morbidity symptoms of anxiety disorders, for example, disturbed sleep, somatic complaints, or decreased quality of life. Except for mild gastrointestinal symptoms, the drug was devoid of adverse effects and did not cause drug interactions or withdrawal symptoms at daily doses of 80 or 160 mg.

  17. Distribution of orally administered and chronically fed /sup 95m/Tc in Japanese quail tissues and eggs

    International Nuclear Information System (INIS)

    Thomas, J.M.; Cadwell, L.L.; Garland, T.R.; Cataldo, D.A.

    1984-10-01

    Previous coefficients for transfer of technetium from feed to poultry have utilized default values. These investigations examined the uptake and distribution of /sup 95m/Tc in male and female Japanese quail following their ingestion of Tc incorporated into alfalfa during growth. Approximately 8% of the daily ingested Tc was transferred to eggs. Biological half-time was one to two days. After 10 days of feeding, 80% of the Tc was in yolk, 20% in albumin, and less than 1% in shell and associated membranes. The Tc levels in albumin reached a maximum between three and five days, compared to six to seven days for yolk. Laying female quail contained 27% of the daily-ingested Tc compared to 5% for males. However, approximately 23% of the daily female Tc intake was contained in the developing ova and reproductive organs. The highest Tc concentrations were in oocytes of laying hens, followed by the fully formed unlaid egg and the ovaries. The uterine shelled egg contained five times the amount of Tc present in other edible tissues combined. For males, the gizzard contained about 53% of the Tc in other edible tissues, followed by muscle (25%), liver (19%), and heart (3%). The transfer coefficient (pCi/kg edible tissue per pCi/day) for plant-incorporated /sup 95m/Tc was about 0.35 day/kg for both sexes. 17 references, 4 tables

  18. A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

    Science.gov (United States)

    Huxford, K E; Dart, A J; Perkins, N R; Bell, R; Jeffcott, L B

    2017-11-01

    AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (phorses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

  19. The effects of orally administered diacerein on cartilage and subchondral bone in an ovine model of osteoarthritis.

    Science.gov (United States)

    Hwa, S Y; Burkhardt, D; Little, C; Ghosh, P

    2001-04-01

    An ovine model of osteoarthritis (OA) induced by bilateral lateral meniscectomy (BLM) was used to evaluate in vivo effects of the slow acting antiarthritic drug diacerein (DIA) on degenerative changes in cartilage and subchondral bone of the operated joints. Twenty of 30 adult age matched Merino wethers were subjected to BLM in the knee joints and the remainder served as non-operated controls (NOC). Half of the BLM group (n = 10) were given DIA (25 mg/kg orally) daily for 3 mo, then 50 mg/kg daily for a further 6 mo. The remainder of the meniscectomized (MEN) group served as OA controls. Five DIA, 5 MEN, and 5 NOC animals were sacrificed at 3 mo and the remainder at 9 mo postsurgery. One knee joint of each animal was used for bone mineral density (BMD) studies. Osteochondral slabs from the lateral femoral condyle and lateral tibial plateau were cut from the contralateral joint and were processed for histological and histomorphometric examination to assess the cartilage and subchondral bone changes. No significant difference was observed in the modified Mankin scores for cartilage from the DIA and MEN groups at 3 or 9 mo. However, in animals treated with DIA, the thickness of cartilage (p = 0.05) and subchondral bone (p = 0.05) in the lesion (middle) zone of the lateral tibial plateau were decreased relative to the corresponding zone of the MEN group at 3 mo (p = 0.05). At 9 mo subchondral bone thickness in this zone remained the same as NOC but BMD, which included both subchondral and trabecular bone, was significantly increased relative to the NOC group (p = 0.01). In contrast, the subchondral bone thickness of the outer zone of lateral tibial plateau and lateral femoral condyle of both MEN and DIA groups increased after 9 mo, while BMD remained the same as in the NOC. DIA treatment of meniscectomized animals mediated selective responses of cartilage and subchondral bone to the altered mechanical stresses induced across the joints by this procedure. While subchondral bone thickness in tibial lesion sites was reduced, cartilage and bone proliferation at the outer joint margins, a region where osteophyte formation occurred, were enhanced, suggesting that DIA supported the processes of repair and endochondral ossification.

  20. Lack of in vivo embryotoxic and genotoxic activities of orally administered stem bark aqueous extract of Mangifera indica L. (Vimang).

    Science.gov (United States)

    González, J E; Rodríguez, M D; Rodeiro, I; Morffi, J; Guerra, E; Leal, F; García, H; Goicochea, E; Guerrero, S; Garrido, G; Delgado, R; Nuñez-Selles, A J

    2007-12-01

    Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a new natural product with antioxidant, anti-inflammatory and immunomodulatory effects known by the brand name of its formulations as Vimang. Previously, the oral toxicity studies of the extract showed a low toxicity potential up to 2000 mg/kg. This work reports the results about teratogenic and genotoxicologic studies of MSBE. For embryotoxicity study, MSBE (20, 200, or 2000 mg/kg/day) was given to Sprague-Dawley rats by gavage on days 6-15 of gestation. For genotoxicity, MSBE was administered three times during 48 h to NMRI mice. Cyclophosphamide (50 mg/kg) was used as a positive control. No maternal or developmental toxicities were observed when the rats were killed on day 20th. The maternal body-weight gain was not affected. No dose-related effects were observed in implantations, fetal viability or external fetal development. Skeletal and visceral development was similar among fetuses from all groups. No genotoxicity was observed in bone marrow erythrocytes and liver cells after administration. MSBE appears to be neither embryotoxic nor genotoxic as measured by bone marrow cytogenetics in rodents.

  1. 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.

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

    Science.gov (United States)

    Abhari, Khadijeh; Shekarforoush, Seyed Shahram; Hosseinzadeh, Saeid; Nazifi, Saeid; Sajedianfard, Javad; Eskandari, Mohammad Hadi

    2016-01-01

    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. 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. 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+ 10(9) spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 10(9) 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 (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively. Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.

  3. Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function.

    Science.gov (United States)

    Broux, B; De Clercq, D; Decloedt, A; De Baere, S; Devreese, M; Van Der Vekens, N; Ven, S; Croubels, S; van Loon, G

    2016-02-01

    Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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...

  5. Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

    OpenAIRE

    Nikoulina, Svetlana E; Fuchs, Dietmar; Moheno, Phillip

    2012-01-01

    Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Guérin mycobacteria). These compunds modulate the immuno-enzyme indoleamine 2,3-dioxygenase (IDO) and the blood levels of severa...

  6. Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

    Directory of Open Access Journals (Sweden)

    Fuchs D

    2012-02-01

    Full Text Available Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Guérin mycobacteria. These compunds modulate the immuno-enzyme indoleamine 2,3-dioxygenase (IDO and the blood levels of several identified inflammatory cytokines. Recent research into the pathology of diabetes implicates inflammatory factors in the progression of the disease, leading the authors to study its possible control by one of the calcium pterins, dipterinyl calcium pentahydrate (DCP.The investigators tested DCP as a novel therapeutic for type 2 diabetes. Female C57BL/6 J mice with diet-induced obesity were fed a high-fat diet and were administered DCP in 0.4% carboxymethylcellulose for 21 days. Blood glucose was followed during the dosing period, and an oral glucose tolerance test (OGTT was carried out on day 21. Measurements of plasma indoleamine 2,3-dioxygenase metabolites (tryptophan and kynurenine and certain cytokines and chemokines were also taken. DCP 7 mg/kg/day reduced OGTT area under the curve (OGTT/AUC by 50% (P < 0.05. A significant multivariate regression (P = 0.013; R2 = 0.571 of OGTT/AUC was derived from DCP dosage and plasma Trp. Elevated plasma Trp concentration, likely from heterogeneity in diet and/or indoleamine 2,3-dioxygenase activity, was found to correlate with higher OGTT/AUC diabetic measures, possibly via inhibition of histamine degradation. In conclusion, an optimum dose of DCP 7 mg/kg/day significantly improved the OGTT diabetic state in these female diet-induced obese mice.Keywords: diabetes, immunotherapy, oral glucose tolerance test, tryptophan, kynurenine

  7. Failure of orally administered attenuated goose parvovirus strain B to induce a humoral immune response in adult geese.

    Science.gov (United States)

    Kisary, J; Kelemen, M

    1981-01-01

    Two-month-old geese responded with the production of virus neutralising antibodies against virulent goose parvovirus strain B administered either per os or intramuscularly. They were shedding the virus within a short period after exposure. Humoral immune response in geese of the same age was induced by the attenuated goose parvovirus strain B only by intramuscular injection but not with per os administration.

  8. Fate of Transgenic DNA from Orally Administered Bt MON810 Maize and Effects on Immune Response and Growth in Pigs

    Science.gov (United States)

    Walsh, Maria C.; Buzoianu, Stefan G.; Gardiner, Gillian E.; Rea, Mary C.; Gelencsér, Eva; Jánosi, Anna; Epstein, Michelle M.; Ross, R. Paul; Lawlor, Peadar G.

    2011-01-01

    We assessed the effect of short-term feeding of genetically modified (GM: Bt MON810) maize on immune responses and growth in weanling pigs and determined the fate of the transgenic DNA and protein in-vivo. Pigs were fed a diet containing 38.9% GM or non-GM isogenic parent line maize for 31 days. We observed that IL-12 and IFNγ production from mitogenic stimulated peripheral blood mononuclear cells decreased (PGM maize exposure. While Cry1Ab-specific IgG and IgA were not detected in the plasma of GM maize-fed pigs, the detection of the cry1Ab gene and protein was limited to the gastrointestinal digesta and was not found in the kidneys, liver, spleen, muscle, heart or blood. Feeding GM maize to weanling pigs had no effect on growth performance or body weight. IL-6 and IL-4 production from isolated splenocytes were increased (PGM maize while the proportion of CD4+ T cells in the spleen decreased. In the ileum, the proportion of B cells and macrophages decreased while the proportion of CD4+ T cells increased in GM maize-fed pigs. IL-8 and IL-4 production from isolated intraepithelial and lamina propria lymphocytes were also increased (PGM maize. In conclusion, there was no evidence of cry1Ab gene or protein translocation to the organs and blood of weaning pigs. The growth of pigs was not affected by feeding GM maize. Alterations in immune responses were detected; however, their biologic relevance is questionable. PMID:22132091

  9. Influence of hydralazine on the pharmacokinetics of orally administered d-propranolol and lidocaine in conscious dogs.

    Science.gov (United States)

    Heinzow, B G; Somogyi, A; McLean, A J

    1987-03-01

    A study was conducted on the influence of oral coadministration of hydralazine (H) on the pharmacokinetics of d-propranolol (P) and lidocaine (L) in 6 conscious dogs. They were given an oral solution containing P (2 mg/kg) and L (15 mg/kg) alone or together with 25 mg H. Plasma concentrations of P and L and the metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured by specific HPLC methods. Concomitant administration of H caused a significant (p less than 0.05) increase in P peak concentrations (Cmax, 34 +/- 5: 73 +/- 10 ng/ml) and the area under plasma concentration time curve (AUC, 142 +/- 18: 254 +/- 56 ng/ml X hr) of P with significant (p less than 0.05) 24% reduction of the apparent oral clearance. The time to reach peak concentrations (Tmax) and the terminal half life (t1/2 beta) were not altered. In contrast to the pattern seen with P the disposition of L was not affected by H. The change in presystemic clearance of P by H cannot be explained by a general underlying mechanism such as an alteration in liver blood flow alone or portal-systemic shunting, since then the pharmacokinetics of L should parallel those of P. It is speculated that other mechanisms, most likely alteration of P metabolism, are primarily responsible for the observed interaction between P and H.

  10. Lack of nonspecific protection against all-cause nonrotavirus gastroenteritis by vaccination with orally administered rotavirus vaccine.

    Science.gov (United States)

    Grant, Lindsay; Watt, James; Moulton, Lawrence; Weatherholtz, Robert; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine

    2013-06-01

    Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens. Safety and efficacy of the pentavalent bovine-human reassortant rotavirus vaccine were studied in multiple populations, including children of the Navajo and White Mountain Apache tribes in the southwestern United States. Stool specimens were collected from children with AGE and tested for rotavirus using an enzyme immunoassay. Analyses were conducted to detect the presence or absence of a vaccine effect on incidence, severity, and duration of AGE in which rotavirus was not detected. The majority of AGE (N = 558: 472 nonrotavirus vs 86 rotavirus) occurred between August 2002 and March 2004 among children ranging from ages 4 to 23 months. The incidence of nonrotavirus AGE was similar by vaccine groups with an incidence rate ratio of 1.07 (incidence rate ratio = vaccinated/unvaccinated, 95% confidence interval 0.89-1.29). The hazards of first, second, third, or any AGE in which rotavirus was not detected differed little by vaccination status (P > 0.05). Duration of symptoms and severity of nonrotavirus AGE were similar by vaccine group. There was no vaccine effect on frequency or severity of nonrotavirus AGE.

  11. 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.

  12. Fluoride adsorption onto an acid treated lateritic mineral from Kenya ...

    African Journals Online (AJOL)

    1) from Kenya was studied by batch experiments. The effect of acid-treatment of adsorbent and change in temperature, mass of LM-1, pH and selected competing ions was evaluated. The adsorption process was strongly influenced by ...

  13. 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.

  14. Fluoride adsorption onto an acid treated lateritic mineral from Kenya ...

    African Journals Online (AJOL)

    Wambu

    adsorption on commercial activated carbons and alumina. (Chaturvedi et al., 1990), ion-exchange ... chemical composition showed that the adsorbent had a ..... fixed bed packed with granular calcite Water Res., 33: 3395–3402. Onyango MS ...

  15. 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.

  16. 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...... efficient to stimulate body growth and feed intake after weaning, by reducing gastric emptying and intestinal mucosa weight and by increasing feed digestibility....

  17. Absorption, distribution, metabolism and excretion of intravenously and orally administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats

    International Nuclear Information System (INIS)

    Knudsen, G.A.; Jacobs, L.M.; Kuester, R.K.; Sipes, I.G.

    2007-01-01

    Tetrabromobisphenol A bis[2,3-dibromopropyl ether],2,2-bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane is a brominated flame retardant with substantial U.S. production. Due to the likelihood of human exposure to TBBPA-DBPE and its probable metabolites, studies regarding the absorption, distribution, metabolism, and excretion were conducted. Male Fischer-344 rats were dosed with TBBPA-DBPE (20 mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBPA-DBPE, elimination of [ 14 C] equivalents in the feces was extensive and rapid (95% of dose by 36 h). Following repeated daily oral doses for 5 or 10 days, route and rate of elimination was similar to single administrations of TBBPA-DBPE. After IV administration, fecal excretion of [ 14 C] equivalents was much slower (27% of dose eliminated by 36 h, 71% by 96 h). Urinary elimination was minimal ( 1/2β : 24.8 h; CL b : 0.1 mL min -1 . Kinetic constants following oral dosing were: t 1/2α : 2.5 h; t 1/2β : 13.9 h; CL b : 4.6 mL min -1 . Systemic bioavailability was 2.2%. Liver was the major site of disposition following oral or IV administration. After oral administration, 1% of the dose was eliminated in bile in 24 h (as metabolites). In in vitro experiments utilizing hepatocytes or liver microsomal protein, no detectable metabolism of TBBPA-DBPE occurred. These data indicate that TBBPA-DBPE is poorly absorbed from the gastrointestinal tract. Compound which is absorbed is sequestered in the liver, slowly metabolized, and eliminated in the feces

  18. Effect of some drugs on radioprotective effectiveness, toxicity and distribution of 35S-Aminopropyl-aminoethyl-thiophosphate orally administered to mice

    International Nuclear Information System (INIS)

    Grechka, I.I.; Belavina, L.P.; Kalistpatov, G.V.; Zherebchenko, P.G.

    1979-01-01

    Studied was the influence of adreno- adn cholinolytics and cholinomimetic substances on radioprotective effectiveness and toxicity of aminopropyl-aminoehtyl-thiophosphate (APAETP) and distribution thereof among organs after oral and intraperitoneal administration. Atropine and INPEA decrease the toxicity and radioprotectiVe efficiency of APAETP when administered orally and do not influence these properties after intraperitoneal in ection. Deposition of the labelled radioprotector within the organs after oral administration is also indicative that atropine and INPEA can delay the transfer of APAETP from the stomach to the intenstine

  19. Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

    Science.gov (United States)

    Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

    2015-05-01

    The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

  20. The acaricidal speed of kill of orally administered fluralaner against poultry red mites (Dermanyssus gallinae) on laying hens and its impact on mite reproduction.

    Science.gov (United States)

    Brauneis, Maria D; Zoller, Hartmut; Williams, Heike; Zschiesche, Eva; Heckeroth, Anja R

    2017-12-02

    Dermanyssus gallinae, the poultry red mite, is a growing threat to chickens in poultry farms. This nocturnal hematophagous ectoparasite has a rapid rate of proliferation with a negative impact on the birds' health, welfare and productivity resulting in severe economic consequences for poultry farmers. A study was performed with fluralaner, a novel systemic ectoparasiticide, to evaluate its effect on mite vitality and reproduction after oral administration to laying hens. Sixteen healthy hens were randomly allocated to two study groups (n = 8). One group was orally treated with fluralaner by gavage at a dose of 0.5 mg/kg bodyweight twice 7 days apart. The negative control group received no treatment. Hens in each group were repeatedly infested with approximately 200 unfed adult D. gallinae at 1, 5, 8, 12, 15, 19, 22 and 26 days after the initial administration. After infestation and feeding for 2.5 h, 25 engorged mites per hen were collected and incubated in tubes. Mites were assessed for vitality (dead/live) at 4, 8, 12, and 24 h after each infestation. Tubes containing eggs and/or living mites were incubated another 8 days for assessment of mite reproductive capacity. Fluralaner demonstrated a fast speed of kill in mites within 4 h post-infestation for 12 days after treatment initiation. An efficacy (mite mortality) of 98.7-100% was achieved. At 15 days after treatment initiation, 100% efficacy was achieved within 24 h post-infestation, and no mite oviposition occurred during this period. Nineteen days after treatment initiation, the mites' ability to generate nymphs was reduced by 90.8%, which decreased to < 24.1% at later infestations. Fluralaner administered orally to hens twice, 7 days apart, provides efficacy against experimental poultry red mite infestation for at least 2 weeks. The demonstrated rapid speed of kill results in substantial depletion of the mites' oviposition and suggests that fluralaner can be an effective tool in the control of D. gallinae, one of the most urgent problems in poultry farms.

  1. 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

    combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...... and at the end of each day. Both treatments were effective immediately after the first dose and during the subsequent multiple-dose phase. There were no statistically significant differences between ketorolac and Ketogan. The results show that 10-mg doses of ketorolac in intramuscular injections followed by 10......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...

  2. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Effect of orally administered azadirachtin on non-specific immune parameters of goldfish Carassius auratus (Linn. 1758) and resistance against Aeromonas hydrophila.

    Science.gov (United States)

    Kumar, Saurav; Raman, R P; Pandey, P K; Mohanty, Snatashree; Kumar, Abhay; Kumar, Kundan

    2013-02-01

    Modulation of the immune responses using active bio-ingredients as a possible prophylaxis measure has been novel prospect for aquaculture. The present study evaluated the effects of azadirachtin EC 25% on non-specific immune responses in goldfish Carassius auratus and resistance against pathogenic bacteria Aeromonas hydrophila. The experimental trial for effects of azadirachtin on immuno-haematoloical parameters in goldfish was conducted by feeding the various levels of azadirachtin as control T(0) (without azadirachtin), T(1) (0.1%), T(2) (0.2%), T(3) (0.4%), T(4) (0.8%) and T(5) (1.6%) for a period of 28 days. Fishes were challenged with A. hydrophila 28 days post feeding and relative percentage survival (%) was recorded over 14 days post infection. Immuno-haematoloical (total erythrocyte count, total leukocyte count, haemoglobin, packed cell volume, NBT activity, phagocytic activity, serum lysozyme activity, myeloperoxidase activity, total immunoglobulin) and serum biochemical parameters (serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and blood glucose) of fishes were examined at 14 and 28 days of feedings. Fish fed with azadirachtin, showed significantly (p 0.05) in the treatment groups compared to control groups. Azadirachtin at the concentration of 4 g kg(-1) showed significantly (p azadirachtin EC 25% (4 g kg(-1)) showed higher NBT activity, serum lysozyme, protein profiles, leukocyte counts and resistance against A. hydrophila infection and thus, can be used as a potential immunostimulant in aquaculture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Immunogenicity in Swine of Orally Administered Recombinant Lactobacillus plantarum Expressing Classical Swine Fever Virus E2 Protein in Conjunction with Thymosin α-1 as an Adjuvant

    Science.gov (United States)

    Xu, Yi-Gang; Guan, Xue-Ting; Liu, Zhong-Mei; Tian, Chang-Yong

    2015-01-01

    Classical swine fever, caused by classical swine fever virus (CSFV), is a highly contagious disease that results in enormous economic losses in pig industries. The E2 protein is one of the main structural proteins of CSFV and is capable of inducing CSFV-neutralizing antibodies and cytotoxic T lymphocyte (CTL) activities in vivo. Thymosin α-1 (Tα1), an immune-modifier peptide, plays a very important role in the cellular immune response. In this study, genetically engineered Lactobacillus plantarum bacteria expressing CSFV E2 protein alone (L. plantarum/pYG-E2) and in combination with Tα1 (L. plantarum/pYG-E2-Tα1) were developed, and the immunogenicity of each as an oral vaccine to induce protective immunity against CSFV in pigs was evaluated. The results showed that recombinant L. plantarum/pYG-E2 and L. plantarum/pYG-E2-Tα1 were both able to effectively induce protective immune responses in pigs against CSFV infection by eliciting immunoglobulin A (IgA)-based mucosal, immunoglobulin G (IgG)-based humoral, and CTL-based cellular immune responses via oral vaccination. Significant differences (P plantarum/pYG-E2-Tα1 and L. plantarum/pYG-E2, suggesting a better immunogenicity of L. plantarum/pYG-E2-Tα1 as a result of the Tα1 molecular adjuvant that can enhance immune responsiveness and augment specific lymphocyte functions. Our data suggest that the recombinant Lactobacillus microecological agent expressing CSFV E2 protein combined with Tα1 as an adjuvant provides a promising strategy for vaccine development against CSFV. PMID:25819954

  6. Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid.

    Science.gov (United States)

    Al-Salem, Huda S; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf

    2016-04-23

    It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.

  7. 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.

  8. 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 combin......-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.......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...... combination product containing the narcotic analgesic, ketobemidone, plus a spasmolytic agent) by intramuscular injection every 1-6 h as needed for pain. When patients were able to tolerate an oral diet and were expected to respond to oral analgesic medication, based on overall pain sensitivity, they were...

  9. 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

  10. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

  12. Prevention of severe infectious complications after colorectal surgery using preoperative orally administered antibiotic prophylaxis (PreCaution) : study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Mulder, Tessa; Kluytmans-van den Bergh, Marjolein F Q; de Smet, Anne Marie G A; van 't Veer, Nils E; Roos, Daphne; Nikolakopoulos, Stavros; Bonten, Marc J M; Kluytmans, Jan A J W

    2018-01-01

    BACKGROUND: Colorectal surgery is frequently complicated by surgical site infections (SSIs). The most important consequences of SSIs are prolonged hospitalization, an increased risk of surgical reintervention and an increase in mortality. Perioperative intravenously administered antibiotic

  13. Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

    Science.gov (United States)

    Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

    2018-05-01

    CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  14. Effects of BCL oral administation and herbal acupuncture at BL18, BL19 on Liver function changes induced by Alcohol in the mice

    Directory of Open Access Journals (Sweden)

    Sa-Hyun Park

    2002-02-01

    Full Text Available This dissertation was designed to evaluate the effect of BCL(refinded Bambusae Caulis in Liqua-men oral administration and herbal acupuncture on alcohol metabolism and liver function. For this study. mice were damaged by a large quantity of alcohol and received treatment of either BCL 1 mg/kg in oral or BCL 250㎍/kg in herbal acupuncture-BL18 . BL19 bilateral. and then such parameters as GOT. GPT. catalase and superoxide dismustase(CuZn-SOD, Mn-SOD were measured. The results of the experiments were summarized as follows. 1. Compared with control group, the proper degree of alcohol in serum was not significantly differ from oral administration group and herbal acupuncture group. 2. Compared with control group. the activity of GOT in serum was significantly reduced both oral administration and herbal acupuncture group. 3. Compared with control group. the activity of GPT in serum was significantly reduced both oral administration and herbal acupuncture group. 4. The activity of catalase in liver cell tissue, compared with control group. was not sigificantly affected either by oral administration and herbal acupuncture group. 5. The activity of CuZn-SOD in liver cell tissue was not significantly change in herbal acupuncture and oral administration group. The activity of Mn-SOD was significantly increased in oral administration group. while it was not the case in acupuncture group. In conclusion. we consider that BCL oral administration and herbal acupuncture is highly effetive in recovering alcohol metabolism and liver disfunction induced by alcohol.

  15. 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

  16. 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. © 2013 John Wiley & Sons Ltd.

  17. 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.

  18. Divalent metal ion removal from aqueous solution by acid-treated ...

    African Journals Online (AJOL)

    ions determined from the Langmuir isotherm showed that C. indica had the largest sorption capacity for Pb2+ ions and the least sorption for Ni2+. The results also showed that garlic-treatment of C. indica biomass enhanced its sorption capacity for the divalent metal ions, with the enhancement factor varying from 1.22 to 1.44 ...

  19. Adsorption properties and porous structure of sulfuric acid treated bentonites determined - SHORT COMMUNICATION

    Directory of Open Access Journals (Sweden)

    SNEZANA BREZOVSKA

    2005-02-01

    Full Text Available In a previous paper adsorption isotherms of benzene vapor on natural bentonite from Ginovci, Macedonia, and forms acid activated with 10 % and 15 % solutions of hydrochloric were interpreted by means of the Dubinin–Radushkevich–Stoeckli and Dubinin–Astakhov equations; the investigation has been continued with bentonites acid activated with 10 % and 15 % solutions of sulfuric acid where X-ray analysis indicates smaller structural changes. Using the above equations, the heterogeneity of the micropores and the energetic heterogeneity of the bentonites were determined from the differential distribution of the micropore volume with respect to the structural parameter of the equations characterizing the microporous structure and to the molar free energy of adsorption. Activated bentonites obtain bigger pores but also a certain quantity of new small pores appear during acid activation with the higher concentration of acid. The micropore volumes, determined from the adsorption of benzene vapor, of bentonites activated with 10 % and 15 % solution of hydrochloric acid (144.60 cm3 kg-1 and 110.06 cm3 kg-1, respectively, decrease in comparison with that of natural bentonite (162.55 cm3 kgv.1 In contrast, the values of the micropore volume for bentonities treated with 10 % and 15 % solutions of sulfuric acids increase (169.19 cm3 kg-1 and 227.74 cm3 kg-1. That is due to the difference in the structural changes occurring during activation with hydrochloric and sulfuric acids. The values of the free energy of adsorption of benzene vapor for natural bentonite are higher than those of the acid acitivated bentonities, what is in accordance with the structural and porosity changes.

  20. TiO2 activation using acid-treated vermiculite as a support: Characteristics and photoreactivity

    International Nuclear Information System (INIS)

    Jin Ling; Dai Bin

    2012-01-01

    Vermiculite was treated by sulfuric or nitric acid aqueous solutions with different concentration. These modified materials as the promising supports, were used to immobilize TiO 2 . TiO 2 was prepared by the precursor, which was obtained by substituting partly isopropyl alcohol with Cl - in titanium chloride {[Ti(IV)(OR) n Cl m ] (n = 2-3, m = 4 - n)}. The TiO 2 /vermiculite composites were characterized by X-ray diffraction, scanning electron microscopy, and the nitrogen absorption. Their photocatalytic activity was evaluated by removal of methylene blue (MB). The pure anatase type crystalline phase was well deposited on the supports. The concentrations of acid for treatment had a significant influence on pore sizes and surface area of vermiculite. The treatment process changed microstructure of vermiculite, modified its characteristics, and farther improved the catalytic activity and absorption capacity of TiO 2 /vermiculite composites. The treatment effect of nitric acid was superior to that of sulfuric acid.

  1. Characterization by temperature programmed techniques of spent and acid treated vanadium catalysts

    Directory of Open Access Journals (Sweden)

    Iran David Charry

    2011-01-01

    Full Text Available Muestras de V2O5/SiO2-YAl2O3 desactivado durante la producción de ácido sulfúrico se trataron con ácido con el fin de recuperar el vanadio. Los materiales se caracterizaron mediante técnicas de temperatura programada: TPR-H2, TPO-O2, TPD-NH3, y TGA-DTA con el fin de determinar el efecto de las especies responsables de la desactivación en la recuperación del metal. Análisis por DRX y UV-Vis se utilizaron para confirmar algunas señales obtenidas en los perfiles de temperatura programada. Los resultados sugieren que la presencia de sulfovanadatos y óxidos de vanadio en las muestras tratadas hacen difícil recuperar más del 86% del vanadio presente en las muestras de catalizador.

  2. Effect of demineralization on the physiochemical structure and thermal degradation of acid treated indigenous rice husk

    Directory of Open Access Journals (Sweden)

    Aslam Umair

    2016-09-01

    Full Text Available Energy generation from biomass presents some serious problems like slagging, fouling and corrosion of boilers. To address these problems, demineralization of biomass is performed using different leaching agents. This study is focused on determining the influence of leaching agents and leaching time on the physiochemical structure of rice husk during demineralization. Dilute (5% wt solutions of HCl and H2SO4 were used for the demineralization of rice husk separately with leaching time of 15, 60 and 120 minutes. It is shown that H2SO4 exhibited higher removal of alkali and alkaline earth metals (AAEM comparatively as depicted by the 34.2% decrease in ash content along with an increase of 7.10% in the heating value. The acid has been seen to induce more notable changes in physiochemical structure as depicted by the FTIR spectra and SEM micrographs. The thermal degradation behavior of the demineralized rice husk has also been reported.

  3. The effects of alfalfa particle size and acid treated protein on ruminal ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of alfalfa particle size (long vs. fine) and canola meal treated with hydrochloric acid solution (untreated vs treated) on ruminal chemical composition, liquid, particulate, escapable and non escapable phases in Zel sheep. Four ruminally cannulated sheep received a mixed ...

  4. Microwave-acid treated bentonite as adsorbent for removal of radiocobalt from liquid radioactive waste

    International Nuclear Information System (INIS)

    Egamediev, S.; Nurbaeva, D.; Saidova, Z.; Khujaev, S.

    2014-01-01

    Full text : Development of new sorbents and study of its sorption properties is an important task for nuclear waste management. In this study it was examined the ability of modified bentonite clays to sorb 60Co radionuclide with aim to evaluate the possibility of using them as sorbents for treatment of radioactively contaminated solutions. The radioactive tracer technique was used for determination of distribution coefficients and to monitor the modification processes of bentonite

  5. Frequency of different congenital anomalies in prenatally valproic acid treated chick embryos

    International Nuclear Information System (INIS)

    Akhtar, L.; Khan, M.Y.

    2016-01-01

    To determine the frequency of different congenital anomalies in surviving chick embryo on hatching after the prenatal administration of valproic acid by comparing with age-matched controls. Study Design: Experimental study. Place and Duration of Study: Anatomy Department, College of Physicians and Surgeons Pakistan (CPSP) Regional Centre, Islamabad, from February 2010 to February 2011. Material and Methods: Thirty fertilized chicken eggs were injected with valproic acid, incubated and then evaluated for different gross congenital anomalies, on hatching or day 22 of incubation whichever was earlier. Chicks of this group were labeled as experimental group-A. Similarly, another group of thirty fertilized chicken eggs labeled as control group-B, underwent sham treatment using normal saline. The weight and length of alive chicks, the total number of chicks with gross anomalies and the number of different types of gross anomalies in both groups were noted and statistically compared. Results: In control group-B, 28 chicks hatch out on 21 day of hatching with no visible gross deformities. Whereas in experimental group-A, 23 chicks were alive, out of which, 9 chicks were with delayed hatching on 22 days of hatching. The chicks with gross deformities were 8 (p=0.0008) which included: limb abnormalities (i.e. inverted feet) in 6 chicks (p=0.006), eye abnormality (i.e. closed palpebral fissure of both eyes) in 2 chick (p=0.2), 1 chick showed multiple deformities including gastroschisis, closed palpebral fissures and inverted foot (p=0.45). There were behavioral changes in 10 chicks (p=0.0001). There was statistically significant difference in their weights (p=0.03). Conclusion: Prenatal exposure of chick embryos to valproic acid increased the incidence of different gross deformities. (author)

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

    International Nuclear Information System (INIS)

    Fu, Congli; Liu, Shuling; Gong, Tianlong; Gu, Aiqun; Yu, Zili

    2014-01-01

    Highlights: • A new transformation (conversion) mechanism of PTFE surface from a hydrophobicity to a hydrophilicity was proposed through the treatment of KMnO 4 /HNO 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 4 /HNO 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

  7. 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.

  8. The effects of alfalfa particle size and acid treated protein on ruminal ...

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2011-10-17

    Oct 17, 2011 ... received a mixed diet (% of dry matter) consisting of 23.73 alfalfa, 8.70 canola meal, 39.56 wheat straw,. 13.45 beet pulp and 13.45 ... ruminal mean retention time of plastic particles in sheep. (Kaske and Engelhardt .... 13.45 and 13.45% of alfalfa forage, canola meal, wheat straw, beet pulp and barley grain, ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Shamsuddin, Shahidah Arina; Hashim, Uda; Halim, Nur Hamidah Abdul [Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Derman, Mohd Nazree, E-mail: nazree@unimap.edu.my; Tahir, Muhammad Faheem Mohd [Centre of Excellence Geopolymer & Green Technology (CEGeoGTech), School of Material Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Kashif, Muhammad [Faculty of Engineering, Universiti Malaysia Sarawak, 94300, Kota Samarahan, Sarawak (Malaysia); Adam, Tijjani [Faculty of Engineering Technology, Universiti Malaysia Perlis, 02100, Padang Besar, Perlis (Malaysia)

    2016-07-19

    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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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.

  11. Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.

    Science.gov (United States)

    Hara, Yuta; Takuma, Kazuhiro; Takano, Erika; Katashiba, Keisuke; Taruta, Atsuki; Higashino, Kosuke; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

    2015-08-01

    Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

    2016-04-01

    Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

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

    KAUST Repository

    Amr, Issam Thaher; Al-Amer, Adnan M J; Selvin, Thomas P.; Al-Harthi, Mamdouh Ahmed; Girei, Salihu Adamu; Sougrat, Rachid; Atieh, Muataz Ali

    2011-01-01

    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

  15. 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.

  16. The effects of alfalfa particle size and acid treated protein on ruminal ...

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2011-10-17

    Oct 17, 2011 ... changes in canola meal protein (khorasani et al., 1993). ... studies have been done in relation to the effects of different particle size and acid .... taken out during the time of measurement of the saliva secretion rate, the effect of ...

  17. Effects of orally administered chemotherapeutics (quinine, salinomycin) against Henneguya sp. Thelohán, 1892 (Myxozoa: Myxobolidae), a gill parasite in the tapir fish Gnathonemus petersii Günther, 1862 (Teleostei).

    Science.gov (United States)

    Dohle, Angelika; Schmahl, Günter; Raether, Wolfgang; Schmidt, Hartmut; Ritter, Günter

    2002-09-01

    When given orally, quinine or salinomycin cause irreversible damage to the plasmodial developmental stages of Henneguya sp., a gill parasite in the tapir fish Gnathonemus petersii. Naturally infected tapir fish measured 75-169 mm in total length and their total weight ranged over 4.3-11.7 g. The fish bore 7-77 plasmodia in their gill arches. Medicinal food containing either quinine (5 g/1000 g food) or salinomycin (0.075 g/1000 g food) was given once a day to naturally infected fish in a food chain via water fleas ( Daphnia spp) for a period of 3, 6, or 9 days. From the monitored feeding of the tapir fish and weight determinations of the water fleas, it was calculated that gross uptake was 18.5 micro g/kg body weight fish daily for pure salinomycin and was 1.25 mg/kg body weight daily for quinine. After the end of the experiments, the fish were sacrificed and the plasmodia were carefully prepared from the gill arches and processed for transmission electron microscopy. As seen by ultrastructure investigations, for both substances the grade of damage in the parasites correlated positively with the period of application. When quinine was given for a 3-day period, the trophozoite ecto- and endoplasm exerted numerous vacuoles, caused by the drug, and the presporogonous and the pansporoblastic stages were malformed. Following a 6-day period, numerous abortive polar capsules were found in the trophozoite cytoplasm. To a large extent, the limiting membranes of the polaroblasts and valvogenic cells were destroyed. In addition, deep clefts between the polaroblasts, the valvogenic cells and between the two sporoblasts were observed. Following a 9-day treatment, all damage increased and, in addition, generative cells and two-cell stages were no longer detectable. As a first sign for the effects of salinomycin, following a 3-day treatment, a shrinking of the whole plasmodia occurred and the sutures in the pansporoblasts were enlarged. The polar capsules were malformed and the zonar structures of the polar filament were no longer detectable. The sporoplasmosomes were more electron-pale than those of the control samples. After a 9-day treatment, the pansporoblasts were completely destroyed. Under the experimental conditions chosen, both compounds were very well tolerated by the fishes.

  18. Pharmacokinetics and physiologic effects of intramuscularly administered xylazine hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination with orally administered sodium salicylate on biomarkers of pain in Holstein calves following castration and dehorning.

    Science.gov (United States)

    Baldridge, Sarah L; Coetzee, Johann F; Dritz, Steve S; Reinbold, James B; Gehring, Ronette; Havel, James; Kukanich, Butch

    2011-10-01

    To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning. 40 Holstein bull calves from 3 farms. Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated. ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods. SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.

  19. Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages.

    Science.gov (United States)

    Jeong, Hee-Yeong; Choi, Yong-Seok; Lee, Jae-Kang; Lee, Beom-Joon; Kim, Woo-Ki; Kang, Hee

    2017-07-10

    Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.

  20. An in Vitro Assessment of Interaction Between Grape Phylloxera and Indole Acetic Acid Treated Grape Plants Daktulosphaira Vitifolia (FITCH)

    International Nuclear Information System (INIS)

    Makee, H.; Charbaji, T.; Idris, I.; Taher, N.

    2011-01-01

    the Life table of local strain of grape phylloxera was determined to evaluate the relationship between indole acetic acid (IAA) and phylloxera on our local variety Helwani. The study was carried out by applying in vitro dual culture system. The results showed that there was a great variation in mean developmental time, female longevity, number of laid eggs and egg distribution between all IAA concentrations and plant ages. Based on the tested biological parameters of phylloxera, (Helwani) would be unsuitable host for such destructive insect as it became older and when 2mg/1 of IAA was applied to in vitro culture media. (author)

  1. Amino acids composition of mycelial protein of penicillium expansum grown in acid treated rice husk mineral medium

    International Nuclear Information System (INIS)

    Khan, M.Y.; Dahot, M.U.

    2012-01-01

    The aim of the present study was to analyze the amino acids composition of single cell protein of Penicillium expansum . Mycelial biomass was produced when fungus was grown in 0.6N H/sub 2/SO/sub 4/ pretreated rice husk mineral medium incorporated with 0.5% and 1% of nitrogen sources like potassium nitrate, sodium nitrate, ammonium nitrate, peptone, yeast extract, urea, corn steep liquor and ammonium sulphate. It was observed that the growth rate of Penicillium expansum increased with 0.5% sodium nitrate produces 1.390 +- 0.084g/l of mycelial biomass. In the subsequent experiment, fermentation medium was supplemented with 0.5% and 1.0% different sugars (sucrose, glucose, fructose, maltose, galactose, lactose, carboxymethyl-cellulose, starch, mannose, and molasses) at pH 6.0 for 240 hours at 35 +- 2 deg. C in a fermenter. The highest amount of mycelial biomass (5.107 +- 0.169g/l) was obtained with 1% sucrose and followed by 4.953 +- 0.17g/l, 4.808 +- 0.14g/l and 4.844 +- 0.10g/l mycelial biomass using glucose, maltose and galactose, respectively. The mycelial biomass of Penicillium expansum contains essential and non essential amino acids like phospho-serine, serine, valine, aspartic acid, threonine, glutamic acid, glycine, isoleucine, leucine, phenylalanine, alo-lysine, halo-lysine, lysine and arginine. The glutamic acid (3355.0 +- 19.798 mu mol/g mycelia) and proline (785.0 +- 9.899 mu mol/g mycelia) were found in higher concentration than other amino acids produced by Penicillium expansum grown on rice husk supplemented with lactose. (author)

  2. 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.

  3. Enhancement of acid treated g-C3N4sbnd Cu2O photocatalytic activity by PEG under visible light irradiation

    Science.gov (United States)

    Zuo, Shiyu; Xu, Haiming; Liao, Wei; Sun, Lei; Li, Qiang; Zan, Jie; Zhang, Binyang; Li, Dongya; Xia, Dongsheng

    2018-05-01

    In this study, g-C3N4sbnd Cu2O was successfully synthesized in the presence of PEG-400 surfactant via an acid treatment hydrothermal method and a high-temperature calcination method. The structures and properties of as-synthesized samples were characterized using a range of techniques, such as XPS, TEM, PL and BET. The g-C3N4sbnd Cu2O heterojunction exhibits the enhanced photocatalytic performance and high stability. It is revealed that the addition of PEG can promote the heterojunction effect of g-C3N4sbnd Cu2O, effectively improving the crystallinity and specific surface area of the photocatalyst, separation efficiency of photocarriers, and light absorption, thus enhancing the photocatalytic performance.

  4. Effects of oxcarbazepine on monoamines content in hippocampus and head and body shakes and sleep patterns in kainic acid-treated rats.

    Science.gov (United States)

    Alfaro-Rodríguez, Alfonso; González-Piña, Rigoberto; Bueno-Nava, Antonio; Arch-Tirado, Emilio; Ávila-Luna, Alberto; Uribe-Escamilla, Rebeca; Vargas-Sánchez, Javier

    2011-09-01

    The aim of this work was to analyze the effect of oxcarbazepine (OXC) on sleep patterns, "head and body shakes" and monoamine neurotransmitters level in a model of kainic-induced seizures. Adult Wistar rats were administered kainic acid (KA), OXC or OXC + KA. A polysomnographic study showed that KA induced animals to stay awake for the whole initial 10 h. OXC administration 30 min prior to KA diminished the effect of KA on the sleep parameters. As a measure of the effects of the drug treatments on behavior, head and body shakes were visually recorded for 4 h after administration of KA, OXC + KA or saline. The presence of OXC diminished the shakes frequency. 4 h after drug application, the hippocampus was dissected out, and the content of monoamines was analyzed. The presence of OXC still more increased serotonin, 5-hidroxyindole acetic acid, dopamine, and homovanilic acid, induced by KA.

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

    Directory of Open Access Journals (Sweden)

    Giovana M B Veronezi

    Full Text Available 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.

  6. Anticonvulsive and free radical scavenging actions of two herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia elata Bl., in kainic acid-treated rats.

    Science.gov (United States)

    Hsieh, C L; Tang, N Y; Chiang, S Y; Hsieh, C T; Lin, J G

    1999-01-01

    Uncaria rhynchophylla (Miq.) Jack (UR) and Gastrodia elata BI. (GE) are traditional Chinese herbs that are usually used in combination to treat convulsive disorders, such as epilepsy, in China. The aim of this study was to compare the anticonvulsive and free radical scavenging activities of UR alone and UR in combination with GE in rats. For the in vitro studies, brain tissues from 6 male Sprague-Dawley (SD) rats were treated with 120 microg/ml kainic acid (KA), with or without varied concentrations of UR or UR plus GE. For the in vivo studies, male SD rats (6 per group) received intraperitoneal (i.p.) injection of KA 12 mg/kg to induce epileptic seizures and generation of free radicals, with or without oral administration of UR 1 g/kg alone or UR 1 g/kg plus GE 1 g/kg. Epileptic seizures were verified by behavioral observations, and electroencephalography (EEG) and electromyography (EMG) recordings. These results showed that UR alone decreased KA-induced lipid peroxide levels in vitro, whereas UR plus GE did not produce a greater effect than UR alone. UR significantly reduced counts of wet dog shakes (WDS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats and significantly delayed the onset time of WDS, from 27 min in the control group to 40 min in the UR group. UR plus GE did not inhibit seizures more effectively than UR alone, but did further prolong the onset time of WDS to 63 min (P < 0.05 vs. UR alone). UR alone reduced the levels of free radicals in vivo, as measured by lipid peroxidation in the brain and luminol-chemiluminescence (CL) counts and lucigenin-CL counts in the peripheral whole blood, but the combination of GE and UR did not reduce free radical levels more markedly than UR alone. In conclusion, our results indicate that UR has anticonvulsive and free radical scavenging activities, and UR combined with GE exhibit greater inhibition on the onset time of WDS than UR alone. These findings suggest that the anticonvulsive effects of UR and GE may be synergistic. However, the mechanism of interaction between UR and GE remains unknown.

  7. Uncaria rhynchophylla and Rhynchophylline inhibit c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activity in kainic acid-treated rats.

    Science.gov (United States)

    Hsieh, Ching-Liang; Ho, Tin-Yun; Su, Shan-Yu; Lo, Wan-Yu; Liu, Chung-Hsiang; Tang, Nou-Ying

    2009-01-01

    Our previous studies have shown that Uncaria rhynchophylla (UR) can reduce epileptic seizures. We hypothesized that UR and its major component rhynchophylline (RH), reduce epileptic seizures in rats treated with kainic acid (KA) by inhibiting nuclear factor-kappaB (NF-kappaB) and activator-protein-1 (AP-1) activity, and by eliminating superoxide anions. Therefore, the level of superoxide anions and the DNA binding activities of NF-kappaB and AP-1 were measured. Sprague-Dawley (SD) rats were pre-treated with UR (1.0 g/kg, i.p.), RH (0.25 mg/kg, i.p.), or valproic acid (VA, 250 mg/kg, i.p.) for 3 days and then KA was administered intra-peritoneal (i.p.). The results indicated that UR, RH, and VA can reduce epileptic seizures and the level of superoxide anions in the blood. Furthermore, KA was demonstrated to induce the DNA binding activities of NF-kappaB and AP-1. However, these inductions were inhibited by pre-treatment with UR, RH, or VA for 3 days. Moreover, UR and RH were shown to be involved in the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. This study suggested that UR and RH have antiepileptic effects in KA-induced seizures and are associated with the regulation of the innate immune system via a reduction in the level of superoxide anions, JNK phosphorylation, and NF-kappaB activation.

  8. Active application of primer acid on acid-treated enamel: Influence on the bond effectiveness of self-etch adhesives systems.

    Science.gov (United States)

    Araújo, Cíntia Tereza Pimenta; Prieto, Lúcia Trazzi; Costa, Daiane Cristianismo; Bosso, Mariana Avalone; Coppini, Erick Kamiya; Dias, Carlos Tadeu Santos; Paulillo, Luis Alexandre Maffei Sartini

    2017-08-01

    Evaluate the composite-to-enamel bond after passive or active application of self-etching primer systems on polished or pre-etched enamel with phosphoric acid. Two self-etch adhesives systems (SEAS) were used: Clearfil SE Bond and Easy Bond. Third human molars were divided into 8 groups (N = 10). The crown of each tooth was sectioned into halves and the mesial/distal surfaces were used. The adhesives were actively or passively applied on enamel with or without prior phosphoric-acid etching. Resin composite cylinders were built after adhesive application. After stored in relative humidity for 24 hr/37°C the specimens were subjected to microshear test in universal testing a machine at a crosshead speed of 0.5 mm/minute. The results were analyzed with three-way ANOVA and the Tukey test. The enamel-etching pattern was evaluated under SEM. The 2-step SEAS system presented significantly higher adhesive bond strength means (47.37 MPa) than the 1-step (36.87 MPa). A poor enamel- etching pattern was observed in active mode showing irregular and short resin tags, however there was not compromised the bond strength. Active or passive application produced similar values of bond strength to enamel regardless of enamel pretreatment and type of SEAS. © 2017 Wiley Periodicals, Inc.

  9. 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.

  10. Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.

    Science.gov (United States)

    Zhang, Jun; Goering, Peter L; Espandiari, Parvaneh; Shaw, Martin; Bonventre, Joseph V; Vaidya, Vishal S; Brown, Ronald P; Keenan, Joe; Kilty, Cormac G; Sadrieh, Nakissa; Hanig, Joseph P

    2009-08-01

    The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI.

  11. 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.

  12. 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.

  13. 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.

    Science.gov (United States)

    Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

    2013-01-01

    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)-1 β , 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.

  14. 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

    OpenAIRE

    Hsu, Hsin-Cheng; Tang, Nou-Ying; Liu, Chung-Hsiang; Hsieh, Ching-Liang

    2013-01-01

    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,...

  15. [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.

  16. 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). Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Anticonvulsant and sedative effect of Fufang Changniu pills and ...

    African Journals Online (AJOL)

    Results: Gallic acid, liquiritin, cinnamyl alcohol, cinnamic acid and glycyrrhizic acid were detected in. FCP decoction. FCP (50, 100 and 200 mg/kg) showed significant anticonvulsant and sedative effects on epileptic mice induced by MES (p < 0.05) and PTZ (p < 0.05). Moreover, pentobarbital sodium-induced sleeping time ...

  18. The permeability characteristics and interaction of main components from Si-Ni-San in a MDCK epithelial cell monolayer model.

    Science.gov (United States)

    Chen, Ruonan; Shen, Chenlin; Xu, Qingqing; Liu, Yaru; Li, Bo; Huang, Cheng; Ma, Taotao; Meng, Xiaoming; Wu, Maomao; Li, Jun

    2017-07-26

    1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4°C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

  19. Evaluation of selected parameters of rat liver and kidney function ...

    African Journals Online (AJOL)

    Dr. J. T. Ekanem

    grouped into two such that one group was orally administered with 14mg/kg body weight on daily basis for 15days ... The complex nature of human sexual response and penile physiology .... measured by the dye excretion tests, clearance.

  20. Effects of Ascorbic Acid on Reproductive Functions of Male Wistar ...

    African Journals Online (AJOL)

    Effects of Ascorbic Acid on Reproductive Functions of Male Wistar Rats Exposed to Nicotine. ... smoke, and its effects on male reproductive system and fertility are well documented. ... The drugs were orally administered for thirty-five days.

  1. Effect of lithium carbonate on leukocyte number after influence of ionizing radiation. 3. Influence of lithium carbonate on peripheral leukocytes after fractionated caudal half-body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rose, H.; Saul, G.; Kehrberg, G. (Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite))

    1985-01-01

    Fractionated half-body irradiation of rats resulted in leukopenia of the peripheral blood. The decrease of leukocytes was smaller in animals pretreated with an orally administered dose of lithium carbonate for 14 days.

  2. 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...

  3. 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...

  4. Journal of Agriculture and Social Research (JASR) Vol. 8, No. 2, 2008

    African Journals Online (AJOL)

    boycott of red meat and poultry eggs, thereby throwing those involved in this line of business out .... pharmacological amounts of copper have been orally administered to ... reduce the risk of CVD is still a green area waiting to be researched.

  5. Inventory of oral anticancer agents : Pharmaceutical formulation aspects with focus on the solid dispersion technique

    NARCIS (Netherlands)

    Sawicki, E.; Schellens, J. H M; Beijnen, J. H.; Nuijen, B.

    2016-01-01

    Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and

  6. Aqueous Extract of Flueggea leucopyrus Increases Urine Output in ...

    African Journals Online (AJOL)

    FLAE) on the urinary output of rats. Method: Three different doses of FLAE (500, 1000 and 1500 mgkg-1), furosemide (13 mg kg-1 as diuretic reference) and distilled water (as control) were orally administered to healthy adult hydrated rats.

  7. Preclinical Safety Assessment of Standardized Extract of Centella asiatica (L.) Urban Leaves

    OpenAIRE

    Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad

    2015-01-01

    Context: Centella asiatica (CA) leaves extract has been shown therapeutic potential. However, safety information is lacking. Aims: To evaluate acute oral toxicity (AOT), sub-chronic toxicity, and mutagenic potential of standardized extract of CA (L.) Urban leaves (INDCA). Materials and Methods: For the acute toxicity study, INDCA was orally administered to Sprague-Dawley rats at a dose range of 0?2000 mg/kg. For the repeated dose toxicity study, the rats of either sex were orally administered...

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

    OpenAIRE

    Tohda, Chihiro; Nakayama, Natsuki; Hatanaka, Fumiyuki; Komatsu, Katsuko

    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...

  9. Toxicological Evaluation of the Methanol Extract of Gmelina arborea Roxb. Bark in Mice and Rats

    OpenAIRE

    Kulkarni, Y. A.; Veeranjaneyulu, A.

    2012-01-01

    Objective: The present study was designed to evaluate acute and repeated dose toxicity of the methanol extract (ME) of the Gmelina arborea stem bark. Materials and Methods: For the acute toxicity study, ME of G. arborea was orally administered to Swiss albino mice at a dose range of 300–5000 mg/kg. For the repeated dose toxicity study, the Wistar rats of either sex were orally administered with ME of G. arborea at the doses of 300, 1000, and 2000 mg/kg/day for a period of 28 days. The effects...

  10. Structure, Content, and Bioactivity of Food-Derived Peptides in the Body.

    Science.gov (United States)

    Sato, Kenji

    2018-03-28

    Orally administered peptides are assumed to be degraded into amino acids in the body. However, our recent studies revealed some food-derived prolyl and pyroglutamyl peptides with 2-3 amino acid residues in the blood of humans and animals, while most of the peptides in the endoproteinase digest of food protein are degraded by exopeptidase. Some food-derived dipeptides in the body display in vitro and in vivo biological activities. These facts indicate that the biological activities of food-derived peptides in the body rather than those in food are crucial to understanding the mechanism of the beneficial effects of orally administered peptides.

  11. 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...

  12. Radioiodine uptake measurements in thyroid

    International Nuclear Information System (INIS)

    Kadireshn, A.; Kapur, S.C.; Samuel, J.R.; Mahajan, M.K.

    1988-01-01

    Evaluation of thyroid function can be carried out by measuring the uptake of orally administered radioactive iodine. The results of the thyroid uptake measurements for the period 1982-1987 in Christian Medical College, Ludhiana are presented here. About 3000 patients were screened during the analysis period. (author)

  13. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    This study was carried out qualitatively and quantitatively to investigate the presence and the concentrations of anabolic steroids in urine collected from orally administered humans. Microanalysis of conjugated steroids by gas chromatography and mass spectrometry (GC/MS) has been carried out. Following oral ...

  14. Haematinic activity of Hibiscus Cannabinus | Agbor | African Journal ...

    African Journals Online (AJOL)

    The haematinic activity of an orally administered aqueous extract of Hibiscus cannabinus leaves was studied on haemolytic anaemic rats. Anaemia was induced by an oral administration of phenylhydrazine for a period of 8 days. Red blood cell count, haemoglobin concentration, and pack cell volume were analysed as ...

  15. Comparison between fish and linseed oils administered orally for ...

    African Journals Online (AJOL)

    The objective of this study was to compare the efficacy of two sources of omega 3 and 6, fish oil (FO) and linseed oil (LO), orally administered, alone or in combination, for treating experimentally induced keratoconjunctivitis sicca (KCS) in rabbits. Twenty-eight New Zealand rabbits were used in this study. Seven animals ...

  16. Stress effect on humoral and cell mediated immune response: Indispensable part of corticosterone and cytokine in neutrophil function

    Directory of Open Access Journals (Sweden)

    Sakthivel Srinivasan

    2016-01-01

    Conclusion: This result further concludes that prior immunization of SRBC in animal’s act as a vaccination, which helps to prevent noise stress induced impairment in immune system. Orally administered I. tinctoria prevented noise altered immune system. These results also concluded that I. tinctoria supplementation could act as an immunomodulators and suggesting its therapeutic efficacy as an antistressor.

  17. Diuretic Activity of Rubus idaeus L (Rosaceae) in Rats

    African Journals Online (AJOL)

    Erah

    291). Diuretic test. Diuretic activity was determined, following the methods of Kawashima [15], but with a minor modification. The rats (48) were fasted for 18 h with free access to drinking water, and then orally administered 30 ml/kg of bicarbonate.

  18. Calcium absorption

    International Nuclear Information System (INIS)

    Carlmark, B.; Reizenstein, P.; Dudley, R.A.

    1976-01-01

    The methods most commonly used to measure the absorption and retention of orally administered calcium are reviewed. Nearly all make use of calcium radioisotopes. The magnitude of calcium absorption and retention depends upon the chemical form and amount of calcium administered, and the clinical and nutritional status of the subject; these influences are briefly surveyed. (author)

  19. Elimination of high-refined-sugar diet as treatment strategy for ...

    African Journals Online (AJOL)

    Purpose: To investigate the potency of ampicillin in altering gut flora in the presence of a high-sucrose diet in rat pups, and to determine its effect on selected neurotransmitters and a cytokine as markers of the persistent autistic features repeatedly induced in orally administered propionic acid rat pups.. Methods: ...

  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, ind...

  1. An overview of once-weekly glucagon-like peptide-1 receptor agonists--available efficacy and safety data and perspectives for the future

    DEFF Research Database (Denmark)

    Madsbad, S; Kielgast, U; Asmar, M

    2011-01-01

    Incretin-based therapies, such as the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and orally administered dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been introduced into clinical practice. At present, the GLP-1 receptor agonists need to be administered once or twice...

  2. 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

  3. Efficacy of some essential oils in mice infected with Trypanosoma cruzi

    African Journals Online (AJOL)

    Purpose: To evaluate the efficacy of orally administered Cymbopogon citratus, Zingiber officinale and Syzygium aromaticum essential oils (EOs) in mice infected with Trypanosoma cruzi. Methods: Three experiments were conducted with 48 Swiss mice each. The animals were inoculated with 2 x 106 metacyclic ...

  4. In vivo, hypolipidemic and antioxidant effects of Citrullus colocynthis ...

    African Journals Online (AJOL)

    ethanol extract on alloxan-induced hyperlipidemia in diabetic rats. 24 albino rats with body weights of 150 to 200 g were divided into one control and three experimental groups. Group 1 was the normal control rats, orally administered ...

  5. Hypoglycemic Effects of Clitoria ternatea Linn. (Fabaceae) in ...

    African Journals Online (AJOL)

    Purpose: This study aims to investigate the therapeutic effects of the aqueous extract of Clitoria ternatea Linn. Fabaceae leaves and flowers on alloxan-induced diabetes in rats. Methods: The effect of orally administered aqueous extracts (400 mg/kg body weight) of Clitoria ternatea leaves and flowers on serum glucose, ...

  6. 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...

  7. Cannabinoids from Cannabis sp.: mechanism of their activity and potential health benefits in human body

    Directory of Open Access Journals (Sweden)

    Grzegorz Dąbrowski

    2017-08-01

    Conclusions: Despite well-documented health effect of marijuana using, cultivation of cannabis is highly restricted by the law. The main obstacles limiting the use of marijuana in medicine are the psychotropic side effects. In this case, the compromise is difficult to achieve. In future, researchers must cooperate to develop orally administered, highly bioavailable, non-psychoactive phytocannabinoid products.

  8. Antitumor activity of Scutellaria baicalensis Georgi total flavonoids ...

    African Journals Online (AJOL)

    The mice models bearing U14 cervical cancer were established in our study and STF were orally administered to mice at a dose of 1000, 500 and 250 mg/kg body weight, respectively. The rate of tumor inhibition was studied, and the cell morphology of tumor, liver and kidney were observed after HE staining. The cell cycle ...

  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.

    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

  10. 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...

  11. 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

  12. Sub-acute toxicity evaluation of ethanol extract of rheumatic tea ...

    African Journals Online (AJOL)

    Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on body weight, ...

  13. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

    NARCIS (Netherlands)

    Willemsen, A.E.C.A.B.; Lubberman, F.J.E.; Tol, J.; Gerritsen, W.R.; Herpen, C.M.L. van; Erp, N. van

    2016-01-01

    Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and

  14. Antimicrobial screening and effect of the pulp extracts of Zizyphus ...

    African Journals Online (AJOL)

    Groups of rats were orally administered 200mg/kg, 400mg/kg and 800mg/kg body weight of extracts daily for three (3) weeks. The animals were sacrificed by decapitation and blood collected for biochemical analysis. The pulp aqueous extract showed more susceptibility on E. coli, P. aeruginosa and C. albicans which is a ...

  15. Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity

    NARCIS (Netherlands)

    Broker, LE; de Vos, FYFL; van Groeningen, CJ; Kuenen, BC; Gall, HE; Woo, MH; Voi, M; Gietema, JA; deVries, EGE; Giaccone, G

    2006-01-01

    Purpose: BMS-275183 is an orally administered C-4 methyl carbonate analogue of paclitaxel. We did a dose-escalating phase I study to investigate its safety, tolerability, pharmacokinetics, and possible antitumor activity. Experimental Design: A cycle consisted of four weekly doses of BMS-275183. The

  16. 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...

  17. Effects Of Extracts Of Telfairia occidental Is Leaves On Some ...

    African Journals Online (AJOL)

    Ethanolic extract of the leaf of Telfairea occidentalis was orally administered to wistar rats for 14 days. On the 15th day the rats were sacrificed and blood was taken from their hearts for analysis. The levels of proteins, hemoglobin, protein fractions, glucose, cholesterol, alanine transaminase (ALAT) and aspartate ...

  18. The Effects of Crude Aqueous and Alcohol Extracts of Aloe Vera on ...

    African Journals Online (AJOL)

    The gastrointestinal tract of neonates is sensitive to dietary manipulations. When nursing mothers use Aloe vera, their babies are at risk of indirect exposure to Aloe vera via breast feeding or directly as health supplements. The effects of orally administered extracts of Aloe vera in unweaned rats were investigated. Six day ...

  19. Astragaloside IV liposomes ameliorates adriamycin-induced ...

    African Journals Online (AJOL)

    Methods: The rats were given a single tail intravenous injection of adriamycin (6 mg/kg) within 1 week, and then divided into four groups including normal, model, benazepril and astragaloside IV liposomes group. They were all orally administered dosage of benazepril and astragaloside IV liposomes once daily for 8 weeks.

  20. Antidiuretic Activity of the Methanol Extract of Aporusa lindleyana ...

    African Journals Online (AJOL)

    Methods: Three doses (500, 1000 and 1500 mg/kg) of the methanol extract (ME) of Aporusa lindleyana (Leaf and bark in 5:1 ratio) were orally administered to female, adult Sprague Dawley rats. Furosemide, vasopressin (antidiuretic hormone) and distilled water were used as diuretic reference, antidiuretic reference and ...

  1. Evaluation of the Diuretic Activity and Phytochemical Screening of ...

    African Journals Online (AJOL)

    Diuretic activity was examined in adult male rats, which were orally administered with aqueous, methanol and ethyl acetate fractions of 80% methanol extract of R. abyssinicus at doses of 250, 500 and 750 mg/kg; furosemide (10 mg/kg) or vehicle. Total urine output and electrolyte content of the urine was computed over 24 ...

  2. Serum total protein, albumin and globulin levels in Trypanosoma ...

    African Journals Online (AJOL)

    The effect of orally administered Scoparia dulcis on Trypanosoma brucei-induced changes in serum total protein, albumin and globulin were investigated in rabbits over a period of twenty eight days. Results obtained show that infection resulted in hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. However ...

  3. Ligation of Cadmium (II) complex by 2,5-diamino-1,3,4-thiadiazole ...

    African Journals Online (AJOL)

    A low value of conductivity revealed the non-electrolytic nature of the compound. The metal chelates possessed greater activities against bacterial strains used compared to the control drug and the ligand used. The study concluded that the metal complex showed mild toxicity at the orally administered dosage-level (0.6 ...

  4. 2124-IJBCS-Article-Jude Okoye

    African Journals Online (AJOL)

    hp

    4Department of Medical Laboratory Services, Federal Medical Centre Gusau, ... This study aimed at investigating the effects of Escravos crude oil on ... and 30 mg kg-1 body weight of Escravos crude oil were orally administered to groups A, B, C, D and ... Estradiol, Anti-Spermatogenesis, Total cholesterol, Chinchilla rabbits.

  5. The Remarkable Beneficial Effect of Adding Oral Simvastatin to ...

    African Journals Online (AJOL)

    Psoriasis is a common chronic inflammatory disease with unpredictable prognosis. Given the immunomodulatory effects of statins, the present study was conducted to determine whether the addition of orally administered simvastatin to the topical betamethasone, a standard antipsoriatic treatment, can produce a more ...

  6. 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...

  7. Effect of repeated administration of Damiana on selected kidney ...

    African Journals Online (AJOL)

    The effect of repeated oral administration of Damiana, an aphrodisiac, on selected renal function indices of male rats for 20 days was investigated. Male rats were orally administered with appropriate volume corresponding to human therapeutic dose of 3.6mg/kg body weight of diamiana at 24hour intervals. The effects on ...

  8. Evaluation of selected parameters of rat liver and kidney function ...

    African Journals Online (AJOL)

    The effects of administration of yohimbine, an aphrodisiac on some functional parameters of rat liver and kidney were investigated. White male albino rats weighing between 200-250g were grouped into two such that one group was orally administered with 14mg/kg body weight on daily basis for 15days while the control ...

  9. Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.

    Science.gov (United States)

    Wojciechowski, Kamil; Orczyk, Marta; Gutberlet, Thomas; Geue, Thomas

    2016-02-01

    The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. The oleanolic acid-type saponins (α-hederin and hederacoside C) were shown to form 1:1 complexes with lipids in bulk, characterized by stability constants in the range (4.0±0.2)·10(3)-(5.0±0.4)·10(4) M(-1). The complexes with cholesterol are generally stronger than those with DPPC. On the contrary, ammonium glycyrrhizate does not form complexes with any of the lipids in solution. The saponin-lipid interactions were also studied in a confined environment of Langmuir monolayers of DPPC and DPPC/cholesterol with the saponins present in the subphase. A combined monolayer relaxation, surface dilational rheology, fluorescence microscopy and neutron reflectivity (NR) study showed that all three saponins are able to penetrate pure DPPC and mixed DPPC/cholesterol monolayers. Overall, the effect of the saponins on the model lipid monolayers does not fully correlate with the lipid-saponin complex formation in the homogeneous solution. The best correlation was found for α-hederin, for which even the preference for cholesterol over DPPC observed in bulk is well reflected in the monolayer studies and the literature data on its membranolytic activity. Similarly, the lack of interaction of ammonium glycyrrhizate with both lipids is evident equally in bulk and monolayer experiments, as well as in its weak membranolytic activity. The combined bulk and monolayer results are discussed in view of the role of confinement in modulating the saponin-lipid interactions and possible mechanism of membranolytic activity of saponins. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Application of an amine functionalized biopolymer in the colonic delivery of glycyrrhizin: a design and in vivo efficacy study.

    Science.gov (United States)

    Kumar De, Amit; Datta, Sriparna; Mukherjee, Arup

    2013-01-01

    In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X1) and guar gum alkyl amine (X2) as the independant variables. The percent cumulative drug release at 240 mins (Q240), 720 mins (Q720), and at 1,440 mins (Q1440) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue's nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.

  11. Determination of asperosaponin VI in dog plasma by high-performance liquid chromatography-tandem mass spectrometry and its application to a pilot pharmacokinetic study.

    Science.gov (United States)

    Shakya, Shailendra; Zhu, He; Ding, Li; Du, Xiao Lang; Qi, Xie Min; Yang, Xiao Lin; Yang, Zhong Lin

    2012-01-01

    A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of asperosaponin VI in beagle dog plasma using glycyrrhizic acid as the internal standard (IS). Plasma samples were simply pretreated with methanol for deproteinization. Chromatographic separation was performed on a Hedera ODS-2 column using mobile phase of methanol-10 mm ammonium acetate buffer solution containing 0.05% acetic acid (71:29, v/v) at a flow rate of 0.38 mL/min. Asperosaponin VI and the IS were eluted at 2.8 and 1.9 min, respectively, ionized in negative ion mode, and then detected by multiple reaction monitoring. The detection used the transitions of the deprotonated molecules at m/z 927.5 → 603.4 for asperosaponin VI and m/z 821.4 → 645.4 for glycyrrhizic acid (IS). The assay was linear over the concentration range of 0.15-700 ng/mL and was successfully applied to a pilot pharmacokinetic study in beagle dogs. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Simultaneous Determination of Nine Active Compounds of the Traditional Chinese Medicinal Prescription Shaoyao-Gancao-Tang and Analysis of the Relationship between Therapeutical Effect and Compatibility of Medicines

    Science.gov (United States)

    Zhang, Guijun; Wang, Meng; Wang, Jingjuan; Zeng, Weixin; Gao, Xiaomei

    2014-01-01

    A simple and sensitive HPLC-DAD detection method was established for the simultaneous determination of nine compounds including oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, glycyrrhizic acid, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in the Traditional Chinese Medicinal Prescription Shaoyao-Gancao-Tang (SGT) and we analyze the relationship between therapeutical effect and compatibility of medicines by using an Agilent extend-C18 column at a flow rate of 1 mL/min. The column temperature was maintained at 30°C and the detection wavelength was set at 230 nm for oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, and glycyrrhizic acid; 276 nm for liquiritin and liquiritigenin; 360 nm for isoliquiritin and isoliquiritigenin. The total contents of the nine compounds in SGT varied from 4.65 to 20.06 mg/mL. The results of this study showed that the content of chemical compounds of Traditional Chinese Medicinal Prescription is mainly influenced by the dosage and compatibility of medicines and the therapeutical effect of Traditional Chinese Medicinal prescription is mainly influenced by the dosage and compatibility of medicines. The method could be suitable for quality control of SGT with bioactive multicompounds. PMID:25431610

  13. [Simultaneous determination of five effective components in Sijunzi bolus using high performance liquid chromatography-evaporation light scattering detection].

    Science.gov (United States)

    Li, Chunying; Zhang, Xiaojun

    2010-01-01

    A high performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of lobetyolin, pachymic acid, glycyrrhizic acid, atractylenoide III and atractylenolide I in Sijunzi bolus. The separation was performed on an HIQ SIL C18 V column (250 mm x 4.6 mm, 5 microm) with 0.5% acetic acid-methanol as the mobile phase of gradient elution at a flow rate of 1.0 mL/min. The detection was performed with an evaporation light scattering detector (ELSD) and the sample volume was 10 microL. The temperature of drift tube and heating grade of nebulizer was respectively set at 55 degrees C and 60% at 0.2 MPa of pressure. Nitrogen gas was used as carrier gas. Under the optimized conditions, there were good linear relationships between the logarithm values of mass concentration and the peak areas of lobetyolin, pachymic acid, glycyrrhizic acid, atractylenoide III and atractylenolide I in the ranges of 0.076 - 1.21, 0.048 -0.76, 0.153 - 2.45, 0.045 - 0.72 and 0.098 - 1.56 g/L, respectively. The recoveries of the five components were between 97.13% and 100.25%, the relative standard deviations (RSDs) were between 1.23% and 2.44%. This method is simple, rapid, accurate and suitable for the quality control of Sijunzi bolus.

  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. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Danneskiold-Samsøe, B; Andersen, R B

    1991-01-01

    S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and anti-depressant effects. Efficacy of 800 mg orally administered s-adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind settings. Tender poi...... effects on primary fibromyalgia and could be an important option in the treatment hereof.......S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and anti-depressant effects. Efficacy of 800 mg orally administered s-adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind settings. Tender point...... = 0.03) and mood evaluated by Face Scale (P = 0.006) in the actively treated group compared to placebo. The tender point score, isokinetic muscle strength, mood evaluated by Beck Depression Inventory and side effects did not differ in the two treatment groups. S-adenosylmethionine has some beneficial...

  16. 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...

  17. 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.

  18. Effects of diethyldithiocarbamate on the toxicokinetics of cadmium chloride in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B

    1989-01-01

    Diethyldithiocarbamate (DDC) efficiently alleviates the acute toxicity of injected cadmium chloride, but enhances the acute toxicity of orally administered cadmium chloride. Further, DDC induces extensive changes in organ distribution of cadmium, and mobilizes aged cadmium depots. The present study...... investigates effects of DDC on the toxicokinetics of cadmium at lower doses of cadmium than those used in previous studies. During single exposure to subtoxic oral doses of cadmium chloride DDC enhanced intestinal cadmium absorption, both after intraperitoneal and oral administration of DDC. In such acute...... exposure experiments orally administered DDC only slightly changed the relative organ distribution of absorbed cadmium, while intraperitoneal administration of DDC induced extensive changes in organ preference of absorbed cadmium. The relative hepatic and testicular deposition was reduced, while...

  19. 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)...

  20. Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments

    DEFF Research Database (Denmark)

    Madsen, Cecilie Maria; Feng, Kung-I; Leithead, Andrew

    2018-01-01

    The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess...... studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound....

  1. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects

    OpenAIRE

    Mueller, F.; Lenz, C.; Dolder, P. C.; Harder, S.; Schmid, Y.; Lang, U. E.; Liechti, M. E.; Borgwardt, S.

    2017-01-01

    Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological pea...

  2. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

    OpenAIRE

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-01-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured s...

  3. Unraveling the Rat Intestine, Spleen and Liver Genome-Wide Transcriptome after the Oral Administration of Lavender Oil by a Two-Color Dye-Swap DNA Microarray Approach

    OpenAIRE

    Kubo, Hiroko; Shibato, Junko; Saito, Tomomi; Ogawa, Tetsuo; Rakwal, Randeep; Shioda, Seiji

    2015-01-01

    The use of lavender oil (LO) – a commonly, used oil in aromatherapy, with well-defined volatile components linalool and linalyl acetate – in non-traditional medicine is increasing globally. To understand and demonstrate the potential positive effects of LO on the body, we have established an animal model in this current study, investigating the orally administered LO effects genome wide in the rat small intestine, spleen, and liver. The rats were administered LO at 5 mg/kg (usual therapeutic ...

  4. Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women

    OpenAIRE

    Tanaka, Miyuki; Misawa,Eriko; Yamauchi,Koji; Abe,Fumiaki; Ishizaki,Chiaki

    2015-01-01

    Miyuki Tanaka,1 Eriko Misawa,1 Koji Yamauchi,1 Fumiaki Abe,1 Chiaki Ishizaki2 1Functional Food Research Department, Food Science and Technology Institute, Morinaga Milk Industry Co, Ltd, Zama, Kanagawa, 2Ebisu Skin Research Center, Inforward, Inc., Tokyo, Japan Background: Aloe is known for its topical use for treating wounds and burns. Many previous studies reported the healing effects of Aloe vera. However, there are few clinical studies on the effect of orally administered A. vera gel on ...

  5. 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.

  6. Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models

    OpenAIRE

    Zopf, Dieter; Fichtner, Iduna; Bhargava, Ajay; Steinke, Wolfram; Thierauch, Karl?Heinz; Diefenbach, Konstanze; Wilhelm, Scott; Hafner, Frank?Thorsten; Gerisch, Michael

    2016-01-01

    Abstract Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment?refractory metastatic colorectal cancer. In clinical studies, steady?state exposure to the M?2 and M?5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of thes...

  7. Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat

    OpenAIRE

    Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

    2016-01-01

    Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1–16 (250 and 500 mg/kg body weight). Six...

  8. Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

    OpenAIRE

    Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

    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...

  9. Engineering Probiotics that Improve Warfighter Performance by Maintaining Lean Body Mass and Inhibiting Anxiety

    Science.gov (United States)

    2017-10-03

    From - To) 03/10/2017 Final Technical Report 15-05-14 to 14-05-17 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Engineering probiotics that improve...ABSTRACT The overall goal of this work is to engineer "synthetic probiotics": orally-administered gut bacteria that sense and compute the metabolic...Final Technical Report Grant number: ONR N00014-14-1-0487 Title: Engineering probiotics that improve warfighter performance by maintaining lean body

  10. Current topics and perspectives in the field of radioprotective compounds

    International Nuclear Information System (INIS)

    Sentenac-Roumanou, H.; Fatome, M.

    1978-01-01

    Since discovery, between 1951 and 1955, of the classical radioprotective agents cysteamine, serotonin and A.E.T., synthesis of more active molecules, long acting polymers and compounds active when orally administered, have been performed, especially during the last decade. On the other hand, extensive investigations on mechanism of action of radioprotective agents and particularly discovery of the essential role displayed by protection of the central nervous system of mammals allowed a marked improvement of concepts in the field of chemical radioprotection [fr

  11. Chemical radioprotection: current data and perspectives

    International Nuclear Information System (INIS)

    Sentenac-Roumanou, H.; Fatome, M.

    1978-01-01

    Since discovery, between 1951 and 1955, of the classical radioprotective agents cysteamine, serotonin and A.E.T., synthesis of more active molecules, long acting polymers and compounds active when orally administered, have been performed, especially during the last decade. On the other hand, extensive investigations on mechanism of action of radioprotective agents and particularly discovery of the essential role displayed by protection of the central nervous system of mammals allowed a marked improvement of concepts in the field of chemical radioprotection [fr

  12. Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis

    OpenAIRE

    Wei, Chen Chao; You, Fan Tian; Mei, Li Yu; Jian, Sun; Qiang, Chen Yong

    2013-01-01

    Background Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. Methods TGP was orally administered for 3?months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chon...

  13. Evaluation of in-vitro antibacterial activity and anti-inflammatory activity for different extracts of Rauvolfia tetraphylla L. root bark

    OpenAIRE

    B. Ganga Rao; P. Umamaheswara Rao; E. Sambasiva Rao; T. Mallikarjuna Rao; V.S. Praneeth. D

    2012-01-01

    Objective: To assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats. Methods: In-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 20...

  14. A Multinational Study to Measure the Value that Patients with Cancer Place on Improved Emesis Control Following Cisplatin Chemotherapy

    OpenAIRE

    George Dranitsaris; Pauline Leung; Renoto Ciotti; Ana Ortega; Maria Spinthouri; Lycurgus Liaropoulos; Roberto Labianca; Antonello Quadri

    2001-01-01

    Background: The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. Objective: To measure the value that patients with cancer place on improved emesis control and quality of life. Design: ...

  15. Vehicle-Dependent Disposition Kinetics of Fluoranthene in Fisher-344 Rats

    OpenAIRE

    Harris, Deacqunita L.; Hood, Darryl B.; Ramesh, Aramandla

    2008-01-01

    The objective of this study was to evaluate how the vehicles of choice affect the pharmacokinetics of orally administered Fluoranthene [FLA] in rats. Fluoranthene is a member of the family of polycyclic aromatic hydrocarbon chemicals. Fluoranthene exposure to humans may occur as a result of cigarette smoking, consumption of contaminated food and water, heating woods in stoves and boilers, industrial sources such as coal gasification, carbon and graphite electrode manufacturing. Adult male Fis...

  16. Antioxidant effect of Arabian coffee ( Coffea arabica L) blended with ...

    African Journals Online (AJOL)

    Purpose: To investigate the antioxidant activity of Coffea Arabica L in high-fat diet (HFD)-fed C57BL/6J mice. Methods: A decoction of Arabian coffee blended with or without cardamom or cloves was orally administered to HFD-fed C57BL/6J mice for a period of 60 days. At the end of the treatment, blood and tissue samples ...

  17. The Antithrombotic and Fibrinolytic Effect of Natto in Hypercholesterolemia Rats

    OpenAIRE

    Park, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Yeo, Ik-Hyun

    2012-01-01

    Antithrombotic and fibrinolytic activity of natto was evaluated on platelet aggregation in vitro and in vivo. Natto showed inhibitory effects on platelet aggregation induced by adenosine 5′diphosphate (ADP) and collagen. Orally administered natto also showed fibrinolytic activity in hypercholesterolemia rats. Normal levels of natto, when administered for four weeks, shortened euglobulin clot lysis time (ECLT) and prolonged partial thromboplastin time (PATT) significantly compared to non-treat...

  18. Oral pharmacokinetics of the acidic drugs, diclofenac and sulfamonomethoxine in male Shiba goats.

    Science.gov (United States)

    Elbadawy, Mohamed; Sakiyama, Takara; Abohatab, Rania; Sasaki, Kazuaki; Shimoda, Minoru

    2015-01-01

    In the present study, we examined the oral pharmacokinetics of the acidic drugs, diclofenac (DF) and sulfamonomethoxine (SMM), which have different physicochemical properties, in Shiba goats. DF and SMM were intravenously and orally administered to 5 male goats using a crossover design. The T(max) of DF and SMM were reached 1.5 and 5.6 hr after they have been orally administered, respectively, and this was followed by their slow elimination. The elimination of both drugs was markedly faster after being intravenously rather than orally administered, which indicated flip-flop phenomena after the oral administration. The mean absorption times (MATs) of DF and SMM were 6 and 15 hr, respectively. This slow absorption may have been due to slow gastric emptying in goats. The large difference observed in MATs between DF and SMM may have been because DF, which is more lipophilic than SMM, was partly absorbed from the forestomach. Therefore, these results suggest that the absorption of highly lipophilic drugs from the forestomach may be markedly high in Shiba goats. In case of drugs whose elimination is quite fast, their efficacies may appear from the early stage after oral administration even in ruminants, because elimination rate is the determinant factor of T(max) in flip-flop phenomena. Such drugs may be used orally even in ruminants.

  19. 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.

  20. Development of polymer film dosage forms of lidocaine for buccal administration. I. Penetration rate and release rate.

    Science.gov (United States)

    Okamoto, H; Taguchi, H; Iida, K; Danjo, K

    2001-12-13

    We examined the penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration.

  1. 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

  2. Semi-quantitative estimation by IR of framework, extraframework and defect Al species of HBEA zeolites.

    Science.gov (United States)

    Marques, João P; Gener, Isabelle; Ayrault, Philippe; Lopes, José M; Ribeiro, F Ramôa; Guisnet, Michel

    2004-10-21

    A simple method based on the characterization (composition, Bronsted and Lewis acidities) of acid treated HBEA zeolites was developed for estimating the concentrations of framework, extraframework and defect Al species.

  3. 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.

  4. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  5. The Mealiness and Quality of Herbal Medicine: Licorice for Example.

    Science.gov (United States)

    Liu, Xueying; Hou, Weilong; Dou, Deqiang

    2017-01-01

    The morphological identification is an effective and simple quality evaluation method in Chinese drugs, and the traits of mealiness and color were widely used in the commercial market of Chinese drugs. The objective of this study was to explore the correlation between mealiness of herbal drugs and its quality; licorice was selected as an example. The mealiness of licorice was graded by its weight; meanwhile, the content of glycyrrhizic acid and liquiritin was determined by high-performance liquid chromatography-diode-array detection method; the content of polysaccharides, soluble sugars, pectin, total starch, amylose, and amylopectin was measured by colorimetric method; and the number and diameter of starch granule were observed by microscope. The results showed that the mealiness of licorice which collected from wild and cultivated plants is positively correlated with the content of glycyrrhizic acid, liquiritin, the ratio of amylose to total starch, and the number of starch granules whose diameter was over 5 μm. However, the mealiness is negatively correlated with the total starch. Further, the formation mechanism of starch granule was discussed. It is for the first time to report the positive correlation between the mealiness and the starch granule size, the ratio of amylose to total starch, which can provide rationality for the quality evaluation using the character of mealiness in herbal medicine. It is a convenient method to justify the quality of herbal medicine. To explore the correlation between mealiness of herbal drugs and its quality, licorice was selected as an example. The result indicated that the effective constituent is correlated with mealiness of licorice. Abbreviations Used: TCM: Traditional Chinese Medicine.

  6. [Simultaneous determination of principal components and related substances of raw material drug of ammonium glycyrrhizinate by reversed-phase high performance liquid chromatography].

    Science.gov (United States)

    Zhao, Yanyan; Liu, Liyan; Han, Yuanyuan; Li, Yueqiu; Wang, Yan; Shi, Minjian

    2013-09-01

    An analytical method for the simultaneous determination of 18alpha-glycyrrhizic acid, 18beta-glycyrrhizinic acid, related substances A and B and drug quality standard by reversed-phase high performance liquid chromatography (RP-HPLC) was established. The assay was carried out on a Durashell-C18 column (250 mm x 4.6 mm, 5 microm) with 10 mmol/L ammonium perchlorate (the pH value was adjusted to 8.20 with ammonia)-methanol (48:52, v/v) as mobile phase at a flow rate of 0.80 mL/min, and the detection wavelength was set at 254 nm. The column temperature was 50 degrees C and the injection volume was 10 microL. Under the separation conditions, the calibration curves of the analytes showed good linearities within the mass concentrations of 0.50 -100 mg/L (r > 0.999 9). The detection limits for 18alpha-glycyrrhizic acid, 18beta-glycyrrhizinic acid, related substances A and B were 0.15, 0.10, 0.10, 0.15 mg/L, respectively. The average recoveries were between 97.32% and 99.33% (n = 3) with the relative standard deviations (RSDs) between 0.05% and 1.06%. The method is sensitive, reproducible, and the results are accurate and reliable. The method can be used for the determination of principal components and related substances of ammonium glycyrrhizinate for the quality control of raw material drug of ammonium glycyrrhizinate.

  7. Effect of Lactobacillus salivarius on growth performance, diarrhea incidence, fecal bacterial population and intestinal morphology of suckling pigs challenged with F4+ enterotoxigenic Escherichia coli.

    Science.gov (United States)

    Sayan, Harutai; Assavacheep, Pornchalit; Angkanaporn, Kris; Assavacheep, Anongnart

    2018-04-12

    Gut health improvements were monitored with respect to growth performance, diarrhea incidence, fecal bacterial population and intestinal morphology of suckling pigs orally supplemented with live Lactobacillus salivarius oral suspensions and challenged with F4+ enterotoxigenic Escherichia coli (ETEC). Two groups of newborn pigs from 18 multiparous sows were randomly designated as non-supplemented (control: n=114 piglets) and L. salivarius supplemented groups (treatment: n=87 piglets). Treatment pigs were orally administered with 2 ml of 109 CFU/ml L. salivarius on days 1 - 3, then they were orally administered with 5 ml of 109 CFU/ml L. salivarius on days 4 - 10, while those in control group received an equal amount of phosphate buffered saline solution (PBS). On day 24 (2 weeks post supplementation), one pig per replicate of both groups was orally administered with 108 CFU/ml F4+ ETEC, then they were euthanized on day 29 of experiment. Results revealed that pigs in treatment group had statistically significant in average daily gain (ADG), body weight and weight gain, and tended to lower diarrhea throughout the study. Numbers of Lactobacillus population in feces of treatment pigs were higher than control pigs, especially on day 10 of study. Numbers of total bacteria in intestinal contents of control pigs were also increased, but not Coliform and Lactobacillus populations. Histological examination revealed statistically significant improvement of villous height and villous/crypt ratio of duodenum, proximal jejunum and distal jejunum parts of treatment pigs better than control. Duodenal pH of treatment group was significantly decreased. Oral supplementation of live L. salivarius during the first 10 days of suckling pig promoted growth performance and guts health, reduced diarrhea incidence, and increased fecal Lactobacillus populations, and improved intestinal morphology.

  8. Potential pharmacokinetic effect of rifampicin on enrofloxacin in broilers: Roles of P-glycoprotein and BCRP induction by rifampicin.

    Science.gov (United States)

    Guo, Mengjie; Dai, Xiaohua; Hu, Dongmin; Zhang, Yu; Sun, Yong; Ren, Weilong; Wang, Liping

    2016-09-01

    P-glycoprotein ( P-GP: , encoding gene Abcb1) and Breast Cancer Resistance Protein ( BCRP: , encoding gene Abcg2) are transport proteins that play a major role in modulating the bioavailability of oral drugs in humans and rodents. It has been shown that rifampicin is the typical inducer of P-gp in rodents by activating the nuclear receptor. However, its effect on Abcb1, Abcg2, CYP3A, and chicken xenobiotic-sensing orphan nuclear receptor ( CXR: ) mRNA expression in broilers is poorly understood. This study explored the effect of rifampicin on mRNA expression of Abcb1, Abcg2, CYP3A37, CXR as well as its effect on the pharmacokinetics of enrofloxacin in broilers. The mRNA levels of Abcb1, Abcg2, CYP3A37, and CXR were significantly increased in the liver (except Abcg2), kidney, jejunum, and ileum (P 0.05) after treated with rifampicin. Further analysis revealed that the variation tendencies of Abcb1, Abcg2, and CYP3A37 expression levels were significantly correlated with CXR mRNA expression levels in liver, kidney, jejunum, and ileum. Coadministration of rifampicin significantly changed the pharmacokinetic behavior of enrofloxacin orally administered by showing clearly lower AUC0-∞, AUC0-t, and Cmax as well as longer Tmax. The bioavailability of orally administered enrofloxacin was decreased from 72.5% to 24.8% by rifampicin. However, rifampicin did not significantly change the pharmacokinetics of enrofloxacin following intravenous administration. Our study shows that rifampicin up-regulated the small intestinal level of P-gp and BCRP and suggests that P-gp and BCRP are key factors that affected pharmacokinetic behavior of orally administered enrofloxacin by limiting its absorption from the intestine in broilers. © 2016 Poultry Science Association Inc.

  9. The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia.

    Science.gov (United States)

    Kaneko, Kumi; Umehara, Masato; Homan, Takashi; Okamoto, Ken; Oka, Michiko; Oyama, Tatsuya

    2014-03-06

    (±)-Tramadol hydrochloride (tramadol) is a widely used analgesic for the treatment of cancer pain and chronic pain. Although many animal studies have shown antinociceptive effects of tramadol in both acute and chronic pain, little is known about the effect of tramadol in putative animal models of fibromyalgia. In this study, we compared the antiallodynic effects of oral administration of tramadol in two kinds of rat chronic pain models, neuropathic pain induced by partial sciatic nerve ligation (PSL) and reserpine-induced myalgia (RIM). In PSL rats, the threshold for responses induced by tactile stimulation with von Frey filaments was significantly decreased seven days after the operation, suggesting that the operation induced tactile allodynia. Orally administered tramadol showed a potent and dose-dependent antiallodynic effect on PSL-induced allodynia. In RIM rats, the threshold was significantly decreased five days after reserpine treatment. Orally administered tramadol also attenuated reserpine-induced tactile allodynia. To explore the mechanism of the antiallodynic effect of tramadol in RIM rats, we investigated the effect of the opioid antagonist naloxone on the tramadol-induced analgesic effect in these rats. The effect of tramadol was partially antagonized by naloxone, suggesting that the opioid receptor is involved at least in part in the antiallodynic effect of tramadol in RIM rats. These data indicate that orally administered tramadol produced improvement in both PSL rats and RIM rats at similar doses and provide evidence that the opioid system is partly involved in the analgesic effect of tramadol in RIM rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. 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.

  11. Small bowel permeability to 51Cr-EDTA in children with recurrent abdominal pain

    International Nuclear Information System (INIS)

    Meer, S.B. van der.; Forget, P.P.

    1990-01-01

    Small bowel permeability was investigated in 87 children with recurrent abdominal pain by measuring the 24-h urinary excretion of orally administered 51 Cr-EDTA. The mean excreation was 3.64% ± 1.49% per 24 h. The difference between the mean urinary excretion in children with recurrent abdominal pain and control children (2.51% ± 0.70%), was significant (p<0.01, two sample t-test). The increased small permeability in children with recurrent abdominal pain might indicate an intestinal etiology for the patients complaints

  12. Persimmon bezoar successfully treated by oral intake of Coca-Cola: a case report.

    Science.gov (United States)

    Hayashi, Kazuki; Ohara, Hirotaka; Naitoh, Itaru; Okumura, Fumihiro; Andoh, Tomoaki; Itoh, Takafumi; Nakazawa, Takahiro; Joh, Takashi

    2008-12-11

    An 82-year-old male presented with a chief complaint of upper abdominal pain. Subsequently, a bezoar and a gastric ulcer were detected by upper gastrointestinal endoscopy. The bezoar was dark green in color and extremely hard, having a major axis of 7 cm. After hospitalization, 500-1000 ml/day of Coca-Cola was orally administered continuously for 3 weeks. Thereafter, the bezoar decreased in size to a major axis of 4 cm and showed a softening trend. Therefore, lithotripsy was thereafter carried out under endoscopy using forceps.

  13. 15N-ammonium test in clinical research

    International Nuclear Information System (INIS)

    Jung, K.; Metzner, C.; Teichmann, B.; Leipzig Univ.

    1989-01-01

    By use of the 15 N-ammonium test the liver function is investigated under influence of hormonal contraceptives in women and in liver diseases in children. With the described noninvasive nonradioactive isotope test the ammonia detoxification capability and the urea synthesis capacity of the liver is determined by measuring of the 15 N excretion in ammonia and urea in urine after oral administering of 15 N-ammonium chloride. The 15 N-ammonium test shows a significant influence of the hormonal contraceptives on the liver function and gives diagnostic evidence for liver diseases in children. (author)

  14. sup 15 N-ammonium test in clinical research. Der ( sup 15 N)-Ammoniumtest in der klinischen Forschung

    Energy Technology Data Exchange (ETDEWEB)

    Jung, K; Metzner, C; Teichmann, B [Akademie der Wissenschaften der DDR, Leipzig (German Democratic Republic). Zentralinstitut fuer Isotopen- und Strahlenforschung Leipzig Univ. (German Democratic Republic). Bereich Medizin

    1989-01-01

    By use of the {sup 15}N-ammonium test the liver function is investigated under influence of hormonal contraceptives in women and in liver diseases in children. With the described noninvasive nonradioactive isotope test the ammonia detoxification capability and the urea synthesis capacity of the liver is determined by measuring of the {sup 15}N excretion in ammonia and urea in urine after oral administering of {sup 15}N-ammonium chloride. The {sup 15}N-ammonium test shows a significant influence of the hormonal contraceptives on the liver function and gives diagnostic evidence for liver diseases in children. (author).

  15. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  16. Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

    Science.gov (United States)

    Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

    2005-01-01

    To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

  17. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers

    OpenAIRE

    Miyake, Mika; Kirisako, Takayoshi; Kokubo, Takeshi; Miura, Yutaka; Morishita, Koji; Okamura, Hisayoshi; Tsuda, Akira

    2014-01-01

    Background L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small. Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals. From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could...

  18. Recycling rate of bile acids in the enterohepatic recirculation as a major determinant of whole body 75SeHCAT retention.

    Science.gov (United States)

    Peters, A Michael; Walters, Julian R F

    2013-10-01

    Measurement of the whole body retention of orally administered (75)SeHCAT is used to investigate patients with unexplained diarrhoea. Retention values of recycling rate of bile acids. Increased recycling has been largely ignored as a cause of BAD, but, as shown in this study, can readily result in excess bile acids reaching the colon even when ileal absorption efficiency is normal (i.e. 95-97 %). There needs to be a re-evaluation of the causes of BAD in patients without a history of previous intestinal resection or evidence of ileal pathology, such as Crohn's disease.

  19. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

    OpenAIRE

    Nakamura, Shigeru; Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

    2017-01-01

    Sea buckthorn (Hippophae rhamnoides)–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, pr...

  20. Intravenøs eller oral N-acetylcysteinbehandling til paracetamolforgiftede patienter. Er det tid til at revurdere behandlingsinstruksen?

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Hanne Rolighed; Dalhoff, Kim

    2010-01-01

    Danish paracetamol (PCM) poisoned patients are treated with N-acetylcysteine (NAC) intravenously for 36 hours. This probably leads to overtreatment. Today, patients with poor prognoses can be identified and, in addition, NAC may have serious side effects. We reviewed the literature (route...... of administration, duration and timing of treatment) and found that intravenous NAC often leads to side effects (some serious), primarily when serum paracetamol is low. These patients are often only mildly poisoned and they may therefore benefit from a shorter, orally administered regimen (equally efficient...

  1. Diclofenac-induced biochemical and histopathological changes in white leghorn birds (Gallus domesticus)

    OpenAIRE

    Jain, Teenu; Koley, K.M.; Vadlamudi, V.P.; Ghosh, R.C.; Roy, S.; Tiwari, Sandhya; Sahu, Upasana

    2009-01-01

    Objective: Objective: To evaluate diclofenac-induced biochemical and histopathological changes in White Leghorn birds. Materials and Methods: Six-week-old birds were equally divided into three groups of six birds each. Group I served as control and received vehicle orally. The birds of Group II and III were orally administered with a single low (2 mg/kg) and high dose (20 mg/kg) of diclofenac sodium, respectively, and were observed for 7 days. The acute toxicity was assessed by observing the ...

  2. Alteration of gastrointestinal transit time in the rat after bile duct cannulation surgery

    International Nuclear Information System (INIS)

    Ayres, P.H.; Medinsky, M.A.; Muggenburg, B.A.; Bond, J.A.

    1985-01-01

    Alteration of gastrointestinal (GI) transit time could affect the bioavailability of a toxicant if the toxicant is absorbed in the GI tract. The effect of surgery on GI transit time was investigated using radiographic imaging of barium during passage through the GI tract of the rat. Bile duct cannulation surgery delayed transit of barium to over 18 h, whereas in the normal animal, transit required approximately 6 h. GI transit time was only moderately affected by laparotomy after an 18-h postsurgery recovery period. These results suggest that the gastrointestinal absorption of orally administered toxicants could be affected by bile duct cannulation. 3 references, 1 figure, 1 table

  3. Clinical studies with oral lipid based formulations of poorly soluble compounds

    DEFF Research Database (Denmark)

    Fatouros, Dimitrios; Karpf, Ditte M; Nielsen, Flemming S

    2007-01-01

    . Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune((R)) and Sandimmune Neoral((R)) (cyclosporin A, Novartis), Norvir((R)) (ritonavir), and Fortovase((R)) (saquinavir) have been formulated in self-emulsifying drug delivery...... systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact...

  4. The importance of localisation within 131J-retention measurements

    International Nuclear Information System (INIS)

    Greifeneder, G.; Aiginger, H.; Steger, F.; Flores, J.

    1996-01-01

    A widely used method to investigate thyroid gland carcinomas, but also disorders of the thyroid gland is the measurement of the 131 J-retention behaviour using a high-sensitivity whole-body counter (HWBC). Normally just the retention of oral administered Radioiodine is controlled. However, it is possible to visualize the distribution of 131 J (using a modified profilescantechnique) beside the retention in the human body and this provides much better information on human metabolism as will be demonstrated in the following

  5. Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

    Science.gov (United States)

    Futatsugi, Kentaro; Kung, Daniel W; Orr, Suvi T M; Cabral, Shawn; Hepworth, David; Aspnes, Gary; Bader, Scott; Bian, Jianwei; Boehm, Markus; Carpino, Philip A; Coffey, Steven B; Dowling, Matthew S; Herr, Michael; Jiao, Wenhua; Lavergne, Sophie Y; Li, Qifang; Clark, Ronald W; Erion, Derek M; Kou, Kou; Lee, Kyuha; Pabst, Brandon A; Perez, Sylvie M; Purkal, Julie; Jorgensen, Csilla C; Goosen, Theunis C; Gosset, James R; Niosi, Mark; Pettersen, John C; Pfefferkorn, Jeffrey A; Ahn, Kay; Goodwin, Bryan

    2015-09-24

    The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

  6. Estimation of plasma tacrine concentrations using an in vitro cholinesterase inhibition assay

    International Nuclear Information System (INIS)

    Moriearty, P.L.; Kenny, W.; Kumar, V.

    1989-01-01

    THA (9-amino, 1,2,3,4-tetrahydroacridine; tacrine) is currently under study as a cholinesterase (ChE) inhibitor in Alzheimer disease. In this study, a sensitive radiometric assay for THA inhibition of human plasma ChE, suitable for detection of effects of orally administered drug, is described. The assay is sensitive in a range of 4-50 ng/ml plasma. Reversibility of the inhibition permits distinguishing of drug effects on ChE from changes in amount of enzyme synthesized during treatment

  7. Antioxidative potential of parsley on gamma irradiated Rats

    International Nuclear Information System (INIS)

    Kafafy, Y.A.; Ashry, M.O.

    2000-01-01

    Phenolic compounds synthesized by plants display significant free radical scavenging capability. This study aims to evaluate the possible anti oxidative potential of parsley on the liver tissue and glycogen as well as serum cholesterol, LDL, HDL, Alkaline. phosphatases, lactic dehydrogenase, glucose and insulin in rats exposed to 9 Gy fractionated gamma irradiation. Parsley oil was orally administered (100 mg/kg body wt) for 7 days before irradiation and throughout the experimental period. The results revealed noticeable limitation of radiation-induced damage in most tested parameters

  8. Intestinal Microbiota in Pediatric Surgical Cases Administered Bifidobacterium Breve: A Randomized Controlled Trial.

    Science.gov (United States)

    Okazaki, Tadaharu; Asahara, Takashi; Yamataka, Atsuyuki; Ogasawara, Yuki; Lane, Geoffrey J; Nomoto, Koji; Nagata, Satoru; Yamashiro, Yuichiro

    2016-07-01

    The efficacy of perioperative probiotic administration has been reported in adults. We examined the effects of orally administered Bifidobacterium breve strain Yakult (BBG-01) on outcomes in pediatric surgical cases by assessing intestinal and blood microbiota. BBG-01 was well tolerated without adverse effects, and postoperative infectious complications were significantly decreased. Fecal analysis showed increased Bifidobacterium and decreased Enterobacteriaceae, Clostridium difficile, and Pseudomonas. Concentrations of fecal acetic acid were significantly increased, maintaining fecal pH at <7.0. The incidence of detecting bacteria in blood was significantly reduced. BBG-01 improved the intestinal environment, and may be implicated in suppressing bacterial translocation.

  9. Intravenøs eller oral N-acetylcysteinbehandling til paracetamolforgiftede patienter. Er det tid til at revurdere behandlingsinstruksen?

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Hanne Rolighed; Dalhoff, Kim

    2010-01-01

    of administration, duration and timing of treatment) and found that intravenous NAC often leads to side effects (some serious), primarily when serum paracetamol is low. These patients are often only mildly poisoned and they may therefore benefit from a shorter, orally administered regimen (equally efficient......Danish paracetamol (PCM) poisoned patients are treated with N-acetylcysteine (NAC) intravenously for 36 hours. This probably leads to overtreatment. Today, patients with poor prognoses can be identified and, in addition, NAC may have serious side effects. We reviewed the literature (route...

  10. 99mTc-sucralfate scintigraphy in inflammatory bowel disease

    International Nuclear Information System (INIS)

    Mortensen, P.B.; Lech, Y.; Moeller-Petersen, J.; Vilien, M.; Fallingborg, J.; Ekelund, S.

    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 99m Tc-albumin-sucralfate scintigraphy is of no value in the detection of inflammatory bowel disease. 8 refs

  11. 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.

  12. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Wen-bin He

    2018-01-01

    Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

  13. Radiation dose estimates for oral agents used in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Siegel, J.A.; Wu, R.K.; Knight, L.C.; Zelac, R.E.; Stern, H.S.; Malmud, L.S.

    1983-01-01

    Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation

  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. Pharmacokinetics of thiamine derivatives especially of benfotiamine.

    Science.gov (United States)

    Loew, D

    1996-02-01

    Pharmacokinetic data of orally administered lipid-soluble thiamine analogues like benfotiamine are reviewed and assessed. It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates. The physiological activity (alphaETK) increased only after benfotiamine was given. Due to its excellent pharmacokinetic profile benfotiamine should be preferred in treatment of relevant indications.

  16. Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative.

    Science.gov (United States)

    Bitsch, R; Wolf, M; Möller, J; Heuzeroth, L; Grüneklee, D

    1991-01-01

    The bioequivalence of thiamin in 2 therapeutically used preparations was tested in 10 healthy young men. Thiamin was orally administered either as lipophilic benfotiamine or as water-soluble thiamin mononitrate. Biokinetic data, measured as area under the curve and maximal concentration in plasma and hemolysate after ingestion, demonstrated a significantly improved bioavailability from the lipophilic derivative despite an ingested dose of only 40% as compared with the water-soluble salt. A superior cellular efficacy of benfotiamine was also concluded from the short-term stimulation of the thiamin-dependent transketolase activity in erythrocytes.

  17. Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

    OpenAIRE

    Kanitani, Masanao; Nishimura, Nobuo; Edamoto, Hiroshi; Kase, Yoshio

    2016-01-01

    Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either s...

  18. Activation of P-glycoprotein and CYP 3A by Coptidis Rhizoma in vivo: Using cyclosporine as a probe substrate in rats

    OpenAIRE

    Chung-Ping Yu; Ching-Ya Huang; Shiuan-Pey Lin; Yu-Chi Hou

    2018-01-01

    Coptidis Rhizoma (CR), the rhizome of Coptis chinensis FRANCH, is a popular Chinese herb. CR contains plenty of isoquinoline alkaloids such as berberine, coptisine and palmatine. Cyclosporine (CSP), an important immunosuppressant with narrow therapeutic window, is employed as a probe substrate of P-glycoprotein (P-gp) and CYP3A4 in order to investigate the in vivo modulation effect of CR on P-gp and CYP3A4. Three groups of rats were orally administered CSP without and with single dose or repe...

  19. Tissue Disposition and Withdrawal Time of Fosfomycin in Swines after Oral and Intramuscular Administration

    OpenAIRE

    Pérez, Denisa Soledad; Soraci, Alejandro Luis; Tapia, Maria Ofelia

    2016-01-01

    A HPLC-MS/MS method, which was suitable to be used in withdrawal time studies, was validated for the determination of fosfomycin in swine muscle, liver, kidney and skin-fat. Therefore, the withdrawal time of fosfomycin in swines, considering a MRL of 0.5 μg/mL was studied. Forty-eight pigs were assigned to two groups; in group one, fosfomycin was orally administered daily with 30 mg⁄kg bw and to the other group a dose of 15 mg⁄kg bw of the antibiotic was intramuscularly administered. Pigs wer...

  20. Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta)

    International Nuclear Information System (INIS)

    Pounds, J.G.; Marlar, R.J.; Allen, J.R.

    1978-01-01

    Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead

  1. 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 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...

  2. A kinetic compartment model for evaluating salivary gland scintigraphies

    DEFF Research Database (Denmark)

    Afzelius, Pia; Fuglsang, Stefan

    2014-01-01

    referred for (99m) Tc-pertechnetate thyroid scintigraphy were studied. Dynamic imaging of the head in a fixed anterior projection was performed after an intravenous bolus injection of 150 MBq (99m) Tc-pertechnetate using a gamma scintillation camera. After 30 min, lemon juice was orally administered...... through a syringe. Time activity curves were generated for each of the four major salivary glands (i.e. the right and left submandibular and right and left parotid glands). Excretion fractions (the fraction of mobilizable radioactivity after administering lemon juice) and the gland activity...

  3. Update on capecitabine alone and in combination regimens in colorectal cancer patients.

    Science.gov (United States)

    Silvestris, N; Maiello, E; De Vita, F; Cinieri, S; Santini, D; Russo, A; Tommasi, S; Azzariti, A; Numico, G; Pisconti, S; Petriella, D; Lorusso, V; Millaku, A; Colucci, G

    2010-11-01

    Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Quantitative mass fragmentographic determination of unlabeled and deuterium-labeled propoxyphene in plasma

    International Nuclear Information System (INIS)

    Sullivan, H.R.; McMahon, R.E.

    1977-01-01

    A quantitative gas chromatographic-mass spectrometric method for determination of plasma levels of d-propoxyphene has been developed by using d-propoxyphene-benzyl-d 7 as internal standard. Steady-state pharmacokinetics were studied in a dog by orally administering d-propoxyphene-d 0 for 19 days and d-propoxyphene-d 2 on the 20th day, and monitoring the plasma levels of both compounds and the ratio for 48 hours. It was established that the use of propoxyphene-d 2 did not lead to an isotope effect

  5. Antibiotic susceptibility of probiotic strains: Is it reasonable to combine probiotics with antibiotics?

    Science.gov (United States)

    Neut, C; Mahieux, S; Dubreuil, L J

    2017-11-01

    The main goal of this study was to determine the in vitro susceptibility of strains collected from marketed probiotics to antibiotics used to treat community-acquired infections. The minimum inhibitory concentrations (MICs) of 16 antibiotics were determined using a gradient strip (E test) or the agar dilution method for fidaxomicin. The probiotics demonstrated various antibiotic patterns. Bacterial probiotics are generally susceptible to most prescribed antibiotics orally administered, whereas yeast probiotics, such as Saccharomyces boulardii, are resistant. Special attention must be paid to co-prescriptions of antibiotics and probiotics to ensure that the probiotic strain is not susceptible. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. 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...

  7. Pharmacological studies of lappaconitine. Analgesic activities.

    Science.gov (United States)

    Ono, M; Satoh, T

    1988-07-01

    The analgesic activity of lappaconitine, which is contained in the root of Aconitum sinomantanum Nakai, was examined after oral and subcutaneous administration to mice or rats by using methods for screening of analgesics, i.e., hot plate, tail immersion, tail pinch, tail pressure, acetic acid-induced writhing, bradykinin-induced flexor reflex of hind limb and Randall-Selitto methods. The results were compared with those for morphine, indometacin and acetylsalicylic acid (ASA). Analgesic activities of lappaconitine were greater than those of indometacin and ASA, but generally about 2 to 5 times less than those of morphine. However, in the rat tail immersion test, orally administered lappaconitine exhibited more potent analgesic activity than morphine; in this test, lappaconitine was almost equipotent when given orally and subcutaneously, whereas the potency of orally administered morphine was only one-twentieth of that of subcutaneously administered morphine. Like morphine, lappaconitine increased the pain threshold of the normal paw as well as that of the inflamed paw when tested by the Randall-Selitto method. The results show that lappaconitine has strong analgesic activity, and further suggest that the central nervous system may be involved in the action on the pain threshold.

  8. Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

    Science.gov (United States)

    Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

    2008-02-04

    The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

  9. Lactoferrin from Milk: Nutraceutical and Pharmacological Properties

    Directory of Open Access Journals (Sweden)

    Francesco Giansanti

    2016-09-01

    Full Text Available Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin’s main function is non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article.

  10. Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

    Science.gov (United States)

    Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

    2018-03-19

    Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

  11. Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

    Science.gov (United States)

    Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan; Kim, Woo Kyoung

    2018-03-01

    Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg.

  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. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

    Science.gov (United States)

    Wehner, S; Vilz, T O; Sommer, N; Sielecki, T; Hong, G S; Lysson, M; Stoffels, B; Pantelis, D; Kalff, J C

    2012-10-01

    Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

  15. Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin in the Blood.

    Science.gov (United States)

    Ozawa, Hitomi; Imaizumi, Atsushi; Sumi, Yoshihiko; Hashimoto, Tadashi; Kanai, Masashi; Makino, Yuji; Tsuda, Takanori; Takahashi, Nobuaki; Kakeya, Hideaki

    2017-01-01

    Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

  16. Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats.

    Science.gov (United States)

    Folarin, Rachael O; Omirinde, Jamiu O; Bejide, Ronald; Isola, Tajudeen O; Usende, Levi I; Basiru, Afisu

    2014-01-01

    This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.

  17. Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR.

    Science.gov (United States)

    Prabhala, Bala K; Aduri, Nanda G; Iqbal, Mazhar; Rahman, Moazur; Gajhede, Michael; Hansen, Paul R; Mirza, Osman

    2017-06-01

    Proton-dependent oligopeptide transporters (POTs) are secondary active transporters found in all kingdoms of life. POTs utilize the proton electrochemical gradient for the uptake of nutrient dipeptides and tripeptides. The human POT hPepT1 is known to transport a number of drugs. As part of ongoing studies on substrate specificities of POTs from Escherichia coli, our aim in this study was to investigate whether bacterial POTs could also transport these drugs. For this, we selected the common orally administered drugs sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir, that are all transported by hPepT1. The transport of these drugs was evaluated using the prototypical POT YdgR from E. coli. The transport studies were pursued through combining cell-based assays with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These investigations revealed that YdgR from E. coli is able to transport five (sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir) drugs. Furthermore, cells not overexpressing YdgR were also able to transport these drugs in a POT-like manner. Orthologues of YdgR are found in several species in the gut microbiome; hence, our findings could have implications for further understanding about the interaction between gut microbes and orally administered drugs. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  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......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 latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington...... between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL...

  19. Laser Acupuncture at Large Intestine 4 Compared with Oral Glucose Administration for Pain Prevention in Healthy Term Neonates Undergoing Routine Heel Lance: Study Protocol for an Observer-Blinded, Randomised Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Jasmin Stadler

    2018-01-01

    Full Text Available Background. Nonpharmacological strategies have actually become more important in neonatal pain management during routinely applied minor painful procedures. However, commonly used nonpharmacological strategies are inferior to orally administered sweet solutions. Therefore, we will compare laser acupuncture, as a recent nonpharmacological method, with the standard care of oral glucose solution for pain prevention. Methods. Ninety-five healthy term neonates will be allocated into one of two groups. Before routine heel lance for metabolic screening, one group will receive laser acupuncture at acupuncture point Large Intestine 4 (LI 4 bilaterally for 60 seconds per point (acupuncture group and the other will receive the standard care with orally administered glucose solution (glucose group. The complete procedure of blood sampling will be recorded on video, excluding the intervention before heel lance. A paediatric nurse, blinded with respect to the allocation, will evaluate these video recordings and determine the Premature Infant Pain Profile (PIPP for each neonate. Primary outcome will be the mean difference in PIPP scores between groups. Discussion. This observer-blinded randomised controlled trial has been designed to explore potential advantages of laser acupuncture in the management of neonatal pain because more data are required to provide information about its efficacy and safety. Trial Registration. This trial is registered with DRKS00010122.

  20. Antioxidative and hypolipidemic efficacy of alcoholic seed extract of Swietenia macrophylla in streptozotocin diabetic rats.

    Science.gov (United States)

    Kalpana, Kalaivanan; Pugalendi, Kodukkur Viswanathan

    2011-06-17

    The present study was designed to examine the antioxidative potential and antihyperlipidemic activity of Swietenia macrophylla in streptozotocin diabetic rats. The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of streptozotocin (STZ; 40 mg/kg body weight, BW). Rats with glucose levels >200 mg/dL were considered diabetic and were divided into five groups. Three groups of diabetic animals were orally administered daily with seed extract (SME) at a dosage of 50, 100 and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and another group orally administered 600 μg/kg BW glibenclamide daily. Repeated daily oral administration of S. macrophylla significantly reduced blood glucose levels after 45 days of treatment. The lipid peroxidation products such as thiobarbituric acid reactive substances and lipid hydroperoxides of SME treated rats decreased in the plasma, liver and kidney. Glutathione peroxidase, superoxide dismutase and catalase activity were significantly increased in SME treated rats. Antioxidants such as reduced glutathione level in the plasma, liver and kidney and vitamins C and E levels in the plasma increased in SME treated rats. Total cholesterol, triglycerides, phospholipids and free fatty acids and lipoproteins levels increased. Altered lipid profile of treated rats lead to normality with treatment of S. macrophylla. Thus, our results indicate that the administration of 100 mg/kg BW SME restores near normal blood glucose, redox status and lipid profile in STZ-diabetic rats.

  1. Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

    Science.gov (United States)

    Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

    2016-05-01

    Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

  2. Polypodium leucotomos as an Adjunct Treatment of Pigmentary Disorders.

    Science.gov (United States)

    Nestor, Mark; Bucay, Vivian; Callender, Valerie; Cohen, Joel L; Sadick, Neil; Waldorf, Heidi

    2014-03-01

    Extracts of the tropical fern Polypodium leucotomos appear to possess beneficial properties for the skin attributed to the presence of numerous compounds within the extract that have antioxidant and photoprotective properties. Orally administered Polypodium leucotomos may provide protection against the detrimental photoaging effects of sunlight and can also help reduce the frequency and severity of polymorphous light eruption. Polypodium leucotomos has also been shown to be beneficial for the prevention and potential treatment of several aesthetically relevant conditions. The purpose of this review is to investigate the beneficial role of Polypodium leucotomos as an adjunct treatment for vitiligo, melasma, and postinflammatory hyperpigmentation. Based on a review of relevant literature including the results of a randomized, placebo-controlled study, the oral administration of Polypodium leucotomos significantly improved the severity of melasma in women after 12 weeks. Three randomized, double-blind, placebo-controlled studies have demonstrated significant improvements in vitiligo when oral Polypodium leucotomos therapy was combined with psoralens plus ultraviolet A and narrowband ultraviolet B. No controlled studies have assessed the efficacy of Polypodium leucotomos for the treatment of postinflammatory hyperpigmentation; however, its known antioxidant and anti-inflammatory properties and demonstrated effectiveness for melasma support its use for treating this condition. No adverse events have been associated with the use of Polypodium leucotomos. In addition to preventing many harmful effects associated with sunlight exposure, orally administered Polypodium leucotomos also appears to provide adjunctive benefits in treating vitiligo, melasma, and may have the potential to help with postinflammatory hyperpigmentation.

  3. 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.

  4. Laser Acupuncture at Large Intestine 4 Compared with Oral Glucose Administration for Pain Prevention in Healthy Term Neonates Undergoing Routine Heel Lance: Study Protocol for an Observer-Blinded, Randomised Controlled Clinical Trial.

    Science.gov (United States)

    Stadler, Jasmin; Avian, Alexander; Posch, Katrin; Urlesberger, Berndt; Raith, Wolfgang

    2018-01-01

    Nonpharmacological strategies have actually become more important in neonatal pain management during routinely applied minor painful procedures. However, commonly used nonpharmacological strategies are inferior to orally administered sweet solutions. Therefore, we will compare laser acupuncture, as a recent nonpharmacological method, with the standard care of oral glucose solution for pain prevention. Ninety-five healthy term neonates will be allocated into one of two groups. Before routine heel lance for metabolic screening, one group will receive laser acupuncture at acupuncture point Large Intestine 4 (LI 4) bilaterally for 60 seconds per point (acupuncture group) and the other will receive the standard care with orally administered glucose solution (glucose group). The complete procedure of blood sampling will be recorded on video, excluding the intervention before heel lance. A paediatric nurse, blinded with respect to the allocation, will evaluate these video recordings and determine the Premature Infant Pain Profile (PIPP) for each neonate. Primary outcome will be the mean difference in PIPP scores between groups. This observer-blinded randomised controlled trial has been designed to explore potential advantages of laser acupuncture in the management of neonatal pain because more data are required to provide information about its efficacy and safety. This trial is registered with DRKS00010122.

  5. Pro blood clotting activity of Scoparia dulcis in rats.

    Science.gov (United States)

    Ediriweera, E R H S S; Jayakody, J R A C; Ratnasooriya, W D

    2011-04-01

    Scoparia dulcis Linn (Family: Scrophulariaceae, Sinhala: WalKoththamalli) is a perennial herb growing in many tropical countries including Sri Lanka. Traditional Physicians in rural down south areas apply crushed S. dulcis plant on cuts and bruises to stop bleeding. S. dulcis may also have Rakta Sthambhana property. The study on effect of decoction (water extract) of S. dulcis on blood clotting time in rats was carried out to investigate this. Two groups of rats, 12 males and 42 females were used in this experimental study. Forty-two female rats were assigned into seven equal groups (n = 6/gp). Different doses of DE (25, 50, 100, 1000, 1500 mg/kg) (group 1-5) or 2 ml of distilled water (DW) (group 6) were orally administered. 0.1 ml of vitamin K was injected intramuscularly (group 7) as reference drug to seventh the group. Twelve male rats were assigned into two equal groups (n = 6/gp), 2 ml of distilled water (DW) and doses of DE (1500 mg/kg) were orally administered. Clotting time was determined on the Days 1, 2, and 7 using Lee and White method. In the DE treated groups with all doses, there was no reduction in clotting time on the Day 1 but a significant reduction of clotting time (P dulcis has proclotting activity (rakthasthambhana property) and this was faster than vitamin K.

  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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Antitumour activity of cordycepin in mice.

    Science.gov (United States)

    Yoshikawa, Noriko; Nakamura, Kazuki; Yamaguchi, Yu; Kagota, Satomi; Shinozuka, Kazumasa; Kunitomo, Masaru

    2004-12-01

    1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculation, the enlarged primary tumour lump was weighed. Cordycepin (0, 5 and 15 mg/kg per day) was administered orally to the mice for 2 weeks from the date of tumour inoculation. Cordycepin (15 mg/kg per day) significantly reduced by 36% the wet weight of the primary tumour lump compared to that of the untreated control mice, without any loss of bodyweight or systemic toxicity. 3. Cordycepin (15 mg/kg per day) administered orally for 2 weeks inhibited the tumour enlargement in the right thigh inoculated with B16-BL6 cells premixed with extracellular matrix (Matrigel). 4. These results indicate that orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.

  9. 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.

  10. Metabolites of hirsuteine and hirsutine, the major indole alkaloids of Uncaria rhynchophylla, in rats.

    Science.gov (United States)

    Nakazawa, Takahiro; Banba, Koh-ichi; Hata, Kazumasa; Nihei, Yutaka; Hoshikawa, Ayumi; Ohsawa, Keisuke

    2006-08-01

    The metabolic fate of hirsuteine (HT) and hirsutine (HS), the major indole alkaloids of Uncaria rhynchophylla, was investigated using rats. On HPLC analysis, urine from rats orally administered HT were found to contain two metabolites (HT1 and HT2) together with unchanged HT. Similarly HS also was metabolized to two compounds (HS1 and HS2). Metabolite structures were determined to be 11-hydroxyhirsuteine-11-O-beta-D-glucuronide (HT1), 11-hydroxyhirsuteine (HT2), 11-hydroxyhirsutine-11-O-beta-D-glucuronide (HS1) and 11-hydroxyhirsutine (HS2), based on spectroscopic and chemical data. HT1 and HS1 were also detected in bile from rats administered HT and HS, respectively. Total cumulative urinary excretion within 72 h of oral administration was approximately 14% and 26% of the HT and HS doses, respectively, while total cumulative biliary excretion was 35% and 46%, respectively. HT and HS 11-hydroxylation were catalyzed by rat liver microsomes. This 11-hydroxylation activity was inhibited by addition of SKF-525A (a nonselective CYP inhibitor) or cimetidine (a CYP2C inhibitor). These results indicate that orally administered HT and HS are converted to 11-hydroxy metabolites in rats, and that the metabolites are predominantly excreted in bile rather than urine following glucuronidation. Furthermore, the results suggest that CYP2C enzymes are involved, at least in part, in the specific 11-hydroxylation of HT and HS.

  11. Hepatoprotective effects of Rauwolfia vomitoria extract on the liver of aduit wistar rats

    Directory of Open Access Journals (Sweden)

    Ezejindu D N

    2013-12-01

    Full Text Available This work focuses primarily on investigating hepatoprotective effects of Rauwolfia vomitoria extract on the liver of adult wistar rats following oral administration. Twenty wistar rats of weights 195 – 215kg were divided into four groups designated as A,B,C and D. Group  A served as the control and were orally administered with 0.4ml of distilled water daily; the experimental groups B,C & D were orally administered with 0.6ml, 0.75ml and 0.81ml of Rauwolfia vomitoria extract for twenty eight days. Twenty four hours after the last administration, the animals were weighed, anasthetized under chloroform vapour and dissected. Liver tissues were removed, weighed and trimmed down for histological studies. The final body weight of the experimental groups (B,C &D increased significantly(P<0.001 with the control. The relative liver weight of the experimental groups B,C &D statistically increased (P<0.001 with the control (A. Histological results showed normal liver architecture in the experimental groups B,C, & D relative to the control (A.  This study therefore suggest that consumption of Rauwolfia vomitoria extract at different doses did not induce hepatotoxicity in the liver of adult wistar rats.

  12. Effects of dithiocarbamates on intestinal absorption and organ distribution of cadmium chloride in mice

    International Nuclear Information System (INIS)

    Andersen, O.; Nielsen, J.B.; Jones, M.M.

    1989-01-01

    Earlier publications have demonstrated that diethyldithiocarbamate (DDC) antagonizes the acute toxicity of injected CdCl 2 but enhances the acute toxicity of orally administered CdCl 2 , most likely due to the high lipophilicity of DDC and the complex formed with the Cd ++ ion. This study demonstrates that the hydrophilic dithiocarbamates dihydroxyethyldithiocarbamate (DHE-DTC) and N-methyl-N-glucamyl dithiocarbamate (NMG-DTC) also enhance the intestinal absorption of orally administered CdCl 2 in mice, although less efficiently than DDC. After oral as well as intraperitoneal administration 15 min. after a single oral dose of CdCl 2 the dithiocarbamates tested enhanced the intestinal cadmium uptake with a relative efficiency, DDC>DHE-DTC>NMG-DTC, which correlated to the lipophilicity of both the dithiocarbamates and the complexes formed with the Cd ++ ion. Intraperitoneal administration of DDC induced extensive changes in the relative organ distribution of absorbed cadmium, compared to the distribution of CdCl 2 administered alone. However, the only noticeable effect of administration of DHE-DTC and NMG-DTC was decreased gastrointestinal deposition of cadmium, irrespective of the administration route of the dithiocarbamates. Earlier studies have demonstrated that DDC and various other dithiocarbamates are capable of mobilizing intracellular cadmium deposits, presumably due to some lipophilicity. This study demonstrates that these dithiocarbamates may also enchance the intestinal absorption of cadmium. (author)

  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. 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

  15. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  16. Effects of functionalization on the targeting site of carbon nanotubes inside cells

    International Nuclear Information System (INIS)

    Porter, A E; Bendall, J S; Welland, M; Gass, M; Muller, K; Skepper, J; Midgley, P

    2010-01-01

    Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging 1 . However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO - functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

  17. Effects of functionalization on the targeting site of carbon nanotubes inside cells

    Energy Technology Data Exchange (ETDEWEB)

    Porter, A E; Bendall, J S; Welland, M [UK SuperSTEM, Daresbury Laboratory, Daresbury, Cheshire WA4 4AD (United Kingdom); Gass, M [The Nanoscience Centre, University of Cambridge, 11 J. J. Thompson Avenue, Cambridge CB3 OFF (United Kingdom); Muller, K; Skepper, J [Multiimaging Centre, Department of PDN, Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY (United Kingdom); Midgley, P, E-mail: a.porter@imperial.ac.u [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)

    2010-07-01

    Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging{sup 1}. However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO{sup -} functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

  18. Infrared spectroscopy and thermal analysis of prepared cation exchangers from cellulosic materials

    International Nuclear Information System (INIS)

    Nada, A.M.A.; EI-Sherief, S.; Nasr, A.; Kamel, M.

    2005-01-01

    Different cation exchangers were prepared by incorporation of phosphate and sulfate groups into acid or alkali treated wood pulp. The molecular structure of these cation exchangers were followed by infrared spectroscopy and thermal degradation analysis technique. From infrared spectra, a new bands are seen at 1200 and 980 cm-1 in phosphorylated wood pulp due to the formation of C-O-P bond. Another bands were seen at 1400, 1200 and 980 cm-1 in phospho sulfonated wood pulp due to the formation of CO- P and C-O-S bonds. Also, it is seen from infrared spectra that the crystallinity index for acid treated wood pulp has a higher value than untreated and alkali treated wood pulp. On the other hand, the acid treated and phosphorylated acid treated wood pulp have a higher activation energy than untreated and phosphorylated alkali treated wood pulp

  19. Effect of acid treatment on thermal extraction yield in ashless coal production

    Energy Technology Data Exchange (ETDEWEB)

    Chunqi Li; Toshimasa Takanohashi; Takahiro Yoshida; Ikuo Saito; Hideki Aoki; Kiyoshi Mashimo [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan). Institute for Energy Utilization

    2004-04-01

    Coals of different ranks were acid-treated in aqueous methoxyethoxy acetic acid (MEAA), acetic acid (AA), and HCl. The acid-treated coals were extracted with polar N-methyl-2-pyrrolidinone (NMP) and nonpolar 1-methylnaphthalene (1MN) solvents at temperatures from 200 to 360{sup o}C for 10 60 min. The thermal extraction yields with NMP for some acid-treated low-rank coals increased greatly; for example, the extraction yield for Wyodak coal (%C; 75.0%) increased from 58.4% for the raw coal to 82.9% for coal treated in 1.0 M MEAA. Conversely, the extraction yields changed minimally for all the acid-treated coals extracted in 1-MN. The type and concentration of acid affected the extraction yield when NMP was used as the extraction solvent. With increasing MEAA concentration from 0.01 to 0.1 M, the extraction yield for Wyodak coal increased from 66.3 to 81.4%, and subsequently did not change clearly with concentration. Similar changes in the extraction yield with acid concentration were also observed with AA and HCl. The de-ashing ratio for coals acid-treated in MEAA, AA, and HCl also increased greatly with concentration from 0.01 to 0.1 M, which corresponded to the change in the thermal extraction yield in NMP. For the acid-treated coals, high extraction yields were obtained at lower extraction temperatures and shorter extraction times than for the raw coal. The mechanisms for the acid treatment and thermal extraction are discussed. 27 refs., 6 figs., 3 tabs.

  20. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis.

    Science.gov (United States)

    Shailubhai, Kunwar; Palejwala, Vaseem; Arjunan, Krishna Priya; Saykhedkar, Sayali; Nefsky, Bradley; Foss, John A; Comiskey, Stephen; Jacob, Gary S; Plevy, Scott E

    2015-11-06

    To evaluate the effect of orally administered plecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models. The cyclic guanosine monophosphate (cGMP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cell-based assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid (5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium (DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic (TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout (TCRα(-/-)) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity. Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C (GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cGMP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs (0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity (P < 0.05) and disease activity index (P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα(-/-) mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. This is the first-ever study reporting

  1. Gastrointestinal absorption and anti-inflammatory effect of bromelain

    Energy Technology Data Exchange (ETDEWEB)

    Izaka, K.I. Yamada, M.; Kawano, T; Suyama, T [Green Cross Corp., Osaka (Japan). Research Lab.

    1972-08-01

    In intraduodenal administration of /sup 125/I bromelain in the dog, a blood radioactive peak was attained at 4 hr, equivalent to 9.2% of the administered radioactivity, but, over 24 hr after the administration, 0.213 to 0.263% of the dose was found in the high molecular serum fraction, 21% of which was respondible for the absorbed as intact, equivalent to 0.042 to 0.052% of the administered. The gastrointestinal absorption immunologically proved the same. In intragastric administration of enteric-coated capsules containing /sup 125/I-bromelain as much as 1/8 th of the intraduodenal dose, the blood level reached the maximum at 6 hr following a 3 hr lag phase, equivalent to 0.6% of the administered, and 0.013% of the dose was attributed to the radioactivity in the high molecular serum fraction. The presence of bromelain absorbed was not evidenced immunologically. In intravenous administration of /sup 125/I-bromelain, /sup 125/I-bromelain was eliminated from the circulation at 50 min half-life, and low /sup 125/I molecules were detected immediately after the administration; it is indicative of the rapid break-down of /sup 125/I-bromelain by serum proteases. A binding of these low /sup 125/I-molecules to serum proteins was also revealed. A 24 hr urinary collection was found 68% of the dose. As for the anti-inflammatory effect of bromelain on the carrageenin-induced edema in the rat hind paw, bromelain orally administered in enteric-coated form showed 6.6% inhibition of edema at 73.5 mg/kg dose, and 39.0% inhibition at 120 mg/kg dose. This effect highly significant and almost equivalent to that obtained with hydrocortisone given at 10 mg/kg dose, while no powdered bromelain orally administered showed an inhibitory effect on the edema at 20 - 300 mg/kg dose level. The data obtained here indicate that orally administered bromelain is absorbable from the gastrointestinal tract and exhibits fairly potent anti-inflammatory activity on the exudative phases in enteric

  2. A review on the role of nutraceuticals as simple as se(2+) to complex organic molecules such as glycyrrhizin that prevent as well as cure diseases.

    Science.gov (United States)

    Jose, Regi; Sajitha, G R; Augusti, K T

    2014-04-01

    Nutraceuticals are nutritional medicines which are present in edible food items. Most of them are antioxidants with various other biological properties viz, anti inflammatory, anti atherogenic, anticancer, anti viral, anti aging properties etc. They are as simple as minerals like Se(2+) to complex organic molecules such as glycyrrhizin (Ca(2+), K(+) salts of glycyrrhizic acid). They can prevent as well as cure various diseases. Most of the medical people are not aware of the importance of the nutraceuticals as such matters are not part of their text books. Many still think that vitamins are the major nutritional medicines. Actually other dietary principles like terpenes, carotenes, phytosterols, polyphenols, flavanoids, di and poly sulphides, their sulfoxides and their precursor amino acids are necessary to scavenge free radicals in the body which are reactive oxygen species to protect and maintain the vitamin levels in the body. They down regulate the activities of those enzymes which are increased in diseases and they increase those that remove oxidants and detoxify carcinogens. They are immune boosters too. Recently glucosinolates, non toxic alkaloids, certain proteins and even fiber are included in the list of nutraceuticals.

  3. Potential role of natural compounds against skin aging.

    Science.gov (United States)

    Tundis, R; Loizzo, M R; Bonesi, M; Menichini, F

    2015-01-01

    Skin aging is an inevitable biological phenomenon of human life. Advancing age brings changes to all components of the integumentary system with consequent signs on the skin. Skin aging is mainly due to intrinsic (chronologic) and extrinsic aging (photo-aging). Photo-aging is a consequence of exposure to ultraviolet radiations. Despite variable economic conditions, the skin care market based on natural products continues to see strong growth. In this context, the research of naturally occurring anti-aging agents is greatly expanding and in recent years numerous plant-derived products have been investigated. This review article focuses on highlighting recent advances in current knowledge on anti-aging natural products grouped and presented according to their family origin. Plants from 35 families were reviewed. A variety of phytomolecules, derived in particular from polyphenols, triterpenes and sterols classes, demonstrated a promising activity. Among them carnosic acid, curculigoside, curcumin, glycyrrhizic acid, mangiferin, mirkoin, asiaticoside, rosmarinic acid, tectorigenin, tyrosol etc., able to inhibit tyrosinase, hyaluronidase, elastase, and collagenase, to scavenge free radicals from skin cells, to prevent trans-epidermal water loss, and to contribute to protect skin from wrinkles, were largely investigated and herein discussed. Extracts and pure compounds from Fabaceae, Asperaceae and Zingiberaceae families have shown particular interest and appear most promising in the development of anti-aging products.

  4. High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation

    Directory of Open Access Journals (Sweden)

    Jihee Kim

    2017-12-01

    Full Text Available Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1 in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK 1/2, protein kinase B (AKT, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE—mitogen-activated protein kinases (MAPK and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

  5. High-Mobility Group Box 1 Mediates Fibroblast Activity via RAGE-MAPK and NF-κB Signaling in Keloid Scar Formation.

    Science.gov (United States)

    Kim, Jihee; Park, Jong-Chul; Lee, Mi Hee; Yang, Chae Eun; Lee, Ju Hee; Lee, Won Jai

    2017-12-28

    Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities. To analyze the downstream mechanism, the protein levels of extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured by western blot analysis. HMGB1 increased the expression levels of ERK1/2, AKT, and NF-κB compared to the control, which was suppressed by GA. HMGB1 promoted both normal and keloid fibroblasts migration to a degree equivalent to that achieved with TGF-β. We concluded that HMGB1 activates fibroblasts via the receptor for advanced glycation end product (RAGE)-mitogen-activated protein kinases (MAPK) and NF-κB interaction signaling pathways. Further knowledge of the relationship of HMGB1 with skin fibrosis may lead to a promising clinical approach to manage abnormal scarring.

  6. Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS

    Directory of Open Access Journals (Sweden)

    Weina Jia

    2015-01-01

    Full Text Available Lianhua-Qingwen capsule (LQC is a commonly used Chinese medical preparation to treat viral influenza and especially played a very important role in the fight against severe acute respiratory syndrome (SARS in 2002-2003 in China. In this paper, a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS method was established for qualitative and quantitative analysis of the major constituents of LQC. A total of 61 compounds including flavonoids, phenylpropanoids, anthraquinones, triterpenoids, iridoids, and other types of compounds were unambiguously or tentatively identified by comparing the retention times and accurate mass measurement with reference compounds or literature data. Among them, twelve representative compounds were further quantified as chemical markers in quantitative analysis, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid. The UPLC-DAD method was evaluated with linearity, limit of detection (LOD, limit of quantification (LOQ, precision, stability, repeatability, and recovery tests. The results showed that the developed quantitative method was linear, sensitive, and precise for the quality control of LQC.

  7. Simultaneous Determination of 11 Compounds in Gualou Guizhi Granule and Pharmacokinetics Study by UPLC-MS/MS

    Directory of Open Access Journals (Sweden)

    Chengtao Sun

    2017-01-01

    Full Text Available A rapid and sensitive ultrafast performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS was developed for the simultaneous determination of 11 compounds in Gualou Guizhi Granule (GLGZG, including liquiritin, isoliquiritin, liquirtin apioside, isoliquiritin apioside, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, paeoniflorin, albiflorin, and paeoniflorin sulfonate in rat plasma. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 × 100 mm, 1.6 μm with the mobile phase consisting of 0.1% aqueous formic acid (A and acetonitrile (B in gradient elution at a flow rate of 0.25 mL·min−1. The method was linear for all analytes within the detection range (r≥0.9597. The inter- and intraday precision (RSD were 2.21–6.41% and 1.67–6.18%; the inter- and intraday accuracy (recover were 92.48–114.03% and 90.23–112.04%. And the recovery rate ranged from 81.30% to 108.22%. The matrix effect values obtained for analytes ranged from 88.91% to 113.32%. This validated method was successfully applied to a pharmacokinetics study in rats after oral administration of GLGZG.

  8. Multi-parameters monitoring during traditional Chinese medicine concentration process with near infrared spectroscopy and chemometrics

    Science.gov (United States)

    Liu, Ronghua; Sun, Qiaofeng; Hu, Tian; Li, Lian; Nie, Lei; Wang, Jiayue; Zhou, Wanhui; Zang, Hengchang

    2018-03-01

    As a powerful process analytical technology (PAT) tool, near infrared (NIR) spectroscopy has been widely used in real-time monitoring. In this study, NIR spectroscopy was applied to monitor multi-parameters of traditional Chinese medicine (TCM) Shenzhiling oral liquid during the concentration process to guarantee the quality of products. Five lab scale batches were employed to construct quantitative models to determine five chemical ingredients and physical change (samples density) during concentration process. The paeoniflorin, albiflorin, liquiritin and samples density were modeled by partial least square regression (PLSR), while the content of the glycyrrhizic acid and cinnamic acid were modeled by support vector machine regression (SVMR). Standard normal variate (SNV) and/or Savitzkye-Golay (SG) smoothing with derivative methods were adopted for spectra pretreatment. Variable selection methods including correlation coefficient (CC), competitive adaptive reweighted sampling (CARS) and interval partial least squares regression (iPLS) were performed for optimizing the models. The results indicated that NIR spectroscopy was an effective tool to successfully monitoring the concentration process of Shenzhiling oral liquid.

  9. HPLC–MS and HPLC–MS/MS analysis of seven active constituents of Xiao-Xu-Ming decoction and application to a pharmacokinetic study after oral administration to rat

    Directory of Open Access Journals (Sweden)

    Yilin Wang

    2012-04-01

    Full Text Available Xiao-xu-ming decoction (XXMD is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae. This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry (HPLC–MS and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide, wogonoside, liquiritigenin, cimifugin, 5-O-methylvisammiol, glycyrrhizic acid and glycyrrhetinic acid in rat plasma. All calibration curves were linear (r >0.99 with lower limits of quantitation (LLOQs<12.4 ng/mL. Intra- and inter-day precisions (as relative standard deviation were all <10.7% with recoveries in the range of 88.7–113%. In addition, the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions. The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.

  10. Effects of space flight on DNA mutation and secondary metabolites of licorice (Glycyrrhiza uralensis Fisch.)

    Institute of Scientific and Technical Information of China (English)

    GAO WenYuan; LI KeFeng; YAN Shuo; GAO XiuMei; HU LiMin

    2009-01-01

    Licorice (Glycyrrhiza uralensis Fisch.) seeds were flown on a recoverable satellite for 18 days(the average radiation dose in the flight recovery module was 0.102 mGy/d, the distance from flight apogee to earth was 350 km, gravity 10~(-6)). After returning to earth, the seeds were germinated and grown to maturity. The parallel ground-based seeds were also planted under the same conditions. The leaves of licorice were used for inter-simple sequence repeat (ISSR) analysis and the two main secondary metabolites in one-year-old roots were analyzed by high performance liquid chromatography (HPLC).Among 22 random primers used in this experiment, 6 primers generated different DNA band types. Analysis of HPLC showed that the content of glycyrrhizic acid (GA) and liquiritin (LQ) in the roots from seeds flown in space was respectively 2.19, 1.18 times higher than that of the control group. The results demonstrated that the extraterrestrial environment induced mutagenic effects on licorice and affected its secondary metabolites. These changes indicated that extraterrestrial orbit is possible means of breeding of licorice so as to preserve this endangered medicinal plant.

  11. Effects of space flight on DNA mutation and secondary metabolites of licorice (Glycyrrhiza uralensis Fisch.)

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Licorice (Glycyrrhiza uralensis Fisch.) seeds were flown on a recoverable satellite for 18 days(the average radiation dose in the flight recovery module was 0.102 mGy/d, the distance from flight apogee to earth was 350 km, gravity 10-6). After returning to earth, the seeds were germinated and grown to maturity. The parallel ground-based seeds were also planted under the same conditions. The leaves of licorice were used for inter-simple sequence repeat (ISSR) analysis and the two main secondary me-tabolites in one-year-old roots were analyzed by high performance liquid chromatography (HPLC). Among 22 random primers used in this experiment, 6 primers generated different DNA band types. Analysis of HPLC showed that the content of glycyrrhizic acid (GA) and liquiritin (LQ) in the roots from seeds flown in space was respectively 2.19, 1.18 times higher than that of the control group. The results demonstrated that the extraterrestrial environment induced mutagenic effects on licorice and affected its secondary metabolites. These changes indicated that extraterrestrial orbit is possible means of breeding of licorice so as to preserve this endangered medicinal plant.

  12. Application of High-Performance Liquid Chromatography Coupled with Linear Ion Trap Quadrupole Orbitrap Mass Spectrometry for Qualitative and Quantitative Assessment of Shejin-Liyan Granule Supplements.

    Science.gov (United States)

    Gu, Jifeng; Wu, Weijun; Huang, Mengwei; Long, Fen; Liu, Xinhua; Zhu, Yizhun

    2018-04-11

    A method for high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) was developed and validated for the qualitative and quantitative assessment of Shejin-liyan Granule. According to the fragmentation mechanism and high-resolution MS data, 54 compounds, including fourteen isoflavones, eleven ligands, eight flavonoids, six physalins, six organic acids, four triterpenoid saponins, two xanthones, two alkaloids, and one licorice coumarin, were identified or tentatively characterized. In addition, ten of the representative compounds (matrine, galuteolin, tectoridin, iridin, arctiin, tectorigenin, glycyrrhizic acid, irigenin, arctigenin, and irisflorentin) were quantified using the validated HPLC-LTQ-Orbitrap MS method. The method validation showed a good linearity with coefficients of determination (r²) above 0.9914 for all analytes. The accuracy of the intra- and inter-day variation of the investigated compounds was 95.0-105.0%, and the precision values were less than 4.89%. The mean recoveries and reproducibilities of each analyte were 95.1-104.8%, with relative standard deviations below 4.91%. The method successfully quantified the ten compounds in Shejin-liyan Granule, and the results show that the method is accurate, sensitive, and reliable.

  13. Identification of a Multicomponent Traditional Herbal Medicine by HPLC-MS and Electron and Light Microscopy.

    Science.gov (United States)

    Liu, Ju-Han; Cheng, Yung-Yi; Hsieh, Chen-Hsi; Tsai, Tung-Hu

    2017-12-15

    Commercial pharmaceutical herbal products have enabled people to take traditional Chinese medicine (TCM) in a convenient and accessible form. However, the quantity and quality should be additionally inspected. To address the issue, a combination of chemical and physical inspection methods were developed to evaluate the amount of an herbal formula, Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT), in clinical TCM practice. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method with electrospray ionization was developed to measure the herbal biomarkers of guanosine, atractylenolide III, glycyrrhizic acid, dehydrocostus lactone, hesperidin, and oleanolic acid from XSLJZT. Scanning electron microscopy (SEM) photographs and light microscopy photographs with Congo red and iodine-KI staining were used to identify the cellulose fibers and starch content. Furthermore, solubility analysis, swelling power test, and crude fiber analysis were contributed to measure the starch additive in pharmaceutical products. The results demonstrated large variations in the chemical components of different pharmaceutical brands. The SEM photographs revealed that the starch was oval, smooth, and granular, and that the raw herbal powder appears stripy, stretched, and filiform. The stained light microscopy photographs of all of the pharmaceutical products showed added starch and raw herbal powder as extenders. The developed chemical and physical methods provide a standard operating procedure for the quantity control of the herbal pharmaceutical products of XSLJZT.

  14. Bioactive activities of natural products against herpesvirus infection.

    Science.gov (United States)

    Son, Myoungki; Lee, Minjung; Sung, Gi-Ho; Lee, Taeho; Shin, Yu Su; Cho, Hyosun; Lieberman, Paul M; Kang, Hyojeung

    2013-10-01

    More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

  15. Application of High-Performance Liquid Chromatography Coupled with Linear Ion Trap Quadrupole Orbitrap Mass Spectrometry for Qualitative and Quantitative Assessment of Shejin-Liyan Granule Supplements

    Directory of Open Access Journals (Sweden)

    Jifeng Gu

    2018-04-01

    Full Text Available A method for high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS was developed and validated for the qualitative and quantitative assessment of Shejin-liyan Granule. According to the fragmentation mechanism and high-resolution MS data, 54 compounds, including fourteen isoflavones, eleven ligands, eight flavonoids, six physalins, six organic acids, four triterpenoid saponins, two xanthones, two alkaloids, and one licorice coumarin, were identified or tentatively characterized. In addition, ten of the representative compounds (matrine, galuteolin, tectoridin, iridin, arctiin, tectorigenin, glycyrrhizic acid, irigenin, arctigenin, and irisflorentin were quantified using the validated HPLC-LTQ-Orbitrap MS method. The method validation showed a good linearity with coefficients of determination (r2 above 0.9914 for all analytes. The accuracy of the intra- and inter-day variation of the investigated compounds was 95.0–105.0%, and the precision values were less than 4.89%. The mean recoveries and reproducibilities of each analyte were 95.1–104.8%, with relative standard deviations below 4.91%. The method successfully quantified the ten compounds in Shejin-liyan Granule, and the results show that the method is accurate, sensitive, and reliable.

  16. Chemomics-Integrated Proteomics Analysis of Jie-Geng-Tang to Ameliorate Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Jin Tao

    2016-01-01

    Full Text Available Jie-Geng-Tang (JGT, a classic and famous traditional Chinese medicine (TCM prescription composed of Platycodon grandiflorum (Jacq. A. DC. (PG and Glycyrrhiza uralensis Fisch. (GU, is well known for “clearing heat and relieving toxicity” and its ability to “diffuse the lung and relieve sore throat.” However, the mechanism underlying its action remains unclear. In this study, potential anti-inflammatory ingredients were screened and submitted to PharmMapper and the KEGG bioinformatics website to predict the target proteins and related pathways, respectively. Differentially expressed candidate proteins from acute lung injury (ALI mice treated with JGT were identified by isobaric tags for relative and absolute quantitation (iTRAQ and LC Triple-TOF. Eleven potential anti-inflammatory ingredients were found, including the derivatives of glycyrrhizic acid, licorice-saponin, liquiritin, and platycodigenin. A total of sixty-seven differentially expressed proteins were confirmed after JGT treatment with four therapeutic functions, including immunoregulation, anti-inflammation, ribosome, and muscle contraction. PG and GU comediate PI3K/Akt signal pathway inhibition of NF-κB, VCAM1, and ICAM1 release which primarily act on PI3K, PDK1, AKT, and GSK3β. GU markedly inhibits the ERK/MAPK signaling pathways and primarily acts on LCK, RAS, and MEK. A network was constructed using bioactive ingredients, targets, and pathways to determine the mechanism underlying JGT treatment of ALI.

  17. Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators

    Directory of Open Access Journals (Sweden)

    Sergio Alberto Bernal-Chávez

    2017-01-01

    Full Text Available The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL and attenuated total reflectance–Fourier transform infrared (ATR-FTIR spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i a reduction on the amount of drug permeated; (ii a reduction in TEWL; and (iii changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

  18. Optimization of the process of aromatic and medicinal plant maceration in grape marc distillates to obtain herbal liqueurs and spirits.

    Science.gov (United States)

    Rodríguez-Solana, Raquel; Vázquez-Araújo, Laura; Salgado, José Manuel; Domínguez, José Manuel; Cortés-Diéguez, Sandra

    2016-11-01

    Herbal liqueurs are alcoholic beverages produced by the maceration or distillation of aromatic and medicinal plants in alcohol, and are also highly valued for their medicinal properties. The process conditions, as well as the number and quantity of the plants employed, will have a great influence on the quality of the liqueur obtained. The aim of this research was to optimize these important variables. A Box-Benhken experimental design was used to evaluate the independent variables: alcohol content, amount of plant and time during the experimental maceration of plants in grape marc distillate. Four plants were assessed, with the main compound of each plant representing the dependent variable evaluated with respect to following the evolution of the maceration process. Bisabolol oxide A in Matricaria recutita L., linalool in Coriander sativum L. and eucalyptol in Eucalyptus globulus Labill. were quantified using a gas chromatography-flame ionization detector. Glycyrrhizic acid in Glycyrrhiza glabra L was determined using a high-performance liquid chromatography-diode array detector. Other dependent variables were also evaluated: total phenolic content, color parameters and consumer preference (i.e. appearance). The experimental designs allowed the selection of the optimal maceration conditions for each parameter, including the preference score of consumers: 70% (v/v) of ethanol, 40 g L -1 plant concentration and a maceration process of 3 weeks. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  19. A systematic summary of natural compounds in Radix Glycyrrhizae

    Directory of Open Access Journals (Sweden)

    Ming Yang

    2018-03-01

    Full Text Available Objective: To accumulate data from studies on the compounds identified from Gancao (Radix Glycyrrhizae, GC, and then systematically summarize and classify these compounds according to their structural characteristics. Methods: Five databases (CNKI, VIP, Wanfang data, CBM, and Pubmed were used to search for studies on the chemical structure of compounds from GC. The retrieval time of the respective databases was from their inception to March 2016. According to the inclusion and exclusion criteria, the papers were carefully screened, and the data were extracted. Results: A total of 653 compounds from GC were collated from 252 articles, including flavonols (n = 201 belonging to 10 subgroups, terpenes and saponins (n = 167, coumarins (n = 30 belonging to 3 subgroups, aliphatics (n = 206, aromatics (n = 35, and others (n = 14. The flavones, represented by liquiritin and liquiritigenin, were the most reported compounds isolated from GC, followed by terpenes and saponins such as glycyrrhizic acid and glycyrrhetinic acid. Conclusion: The more than 600 natural compounds in GC may be responsible for GC’s anti-inflammatory, phlegm-expelling, cough- and pain-relieving activities.

  20. [Optimization of ultrasonic extraction process for Xiaoqinglong granules by Box-Behnken in condition of medium scale].

    Science.gov (United States)

    Wang, Zheng-Kuan; Shi, Xiao-Meng; Liu, Yuan; Zhang, Qing-Fen; Wu, Jian-Xiong; Bi, Yu-An; Wang, Zhen-Zhong; Xiao, Wei

    2016-02-01

    This paper is to investigate the optimization conditions of ultrasonic technique for extraction process of Xiaoqinglong granules in medium scale. First of all, single factor experiment was used to determine the overall impact tendency and range of each factor; secondly, Box-Behnken method was used for optimization and detecting the content of paeoniflorin, ephedrine hydrochloride, glycyrrhizic acid of the liquid medicine. Their respective extraction rate was calculated and the comprehensive evaluation was carried out. The results were used as the evaluation basis for the efficacy of Xiaoqinglong granules ultrasonic extraction. The test results showed that the optimum extraction process of Xiaoqinglong granules by ultrasonic extraction was under the following conditions: ultrasonic power 600 W, liquid-solid ratio 10∶1, extraction for 31 min. Under this condition, the predicted value of extraction rate for Xiaoqinglong granules was 85.90%, and the test value was 85.87%. The mathematical model(P<0.01) established in this paper was significant, and can be used for the analysis and prediction of the ultrasonic extraction process of Xiaoqinglong granules. Copyright© by the Chinese Pharmaceutical Association.

  1. Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi decoction.

    Science.gov (United States)

    Zeng, Jia-Kai; Li, Yuan-Yuan; Wang, Tian-Ming; Zhong, Jie; Wu, Jia-Sheng; Liu, Ping; Zhang, Hua; Ma, Yue-Ming

    2018-05-01

    A rapid, sensitive and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-d-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C 18 column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Ammonia treated Mo/AC catalysts for CO hydrogenation with ...

    Indian Academy of Sciences (India)

    SHARIF F ZAMAN

    the influence of acid treated AC as a support with K-Ni-. Mo active ... K-Ni-Mo/AC catalyst was more selective to oxygenates. (>40% ... mineral impurities (K, Si, Sn and Fe) <1%. ...... edge technical support with thanks Science and Technology.

  3. Binding of Vapour-Phase Mercury (Hg0) on Chemically Treated Bauxite Residues (Red Mud)

    Science.gov (United States)

    In this study, Hg capture using red mud, seawater-neutralized red mud, and acid-treated red mud is evaluated and compared to other, more conventional sorbent materials. Red mud (also known as bauxite residue) is a by-product of extracting alumina from ground bauxite ore by treati...

  4. Stereochemistry of Furfural Reduction by a Saccharomyces cerevisiae Aldehyde Reductase That Contributes to In Situ Furfural Detoxification

    Science.gov (United States)

    Ari1p from Saccharomyces cerevisiae, recently identified as an intermediate subclass short-chain dehydrogenase/reductase, contributes in situ to the detoxification of furfural. Furfural inhibits efficient ethanol production by the yeast, particularly when the carbon source is acid-treated lignocell...

  5. Processing and characterization of biodegradable soy plastics: Effects of crosslinking with glyoxal and thermal treatment

    NARCIS (Netherlands)

    Vaz, C.M.; Doeveren, van P.F.N.M.; Yilmaz, G.; Graaf, de L.A.; Reis, R.L.; Cunha, A.M.

    2005-01-01

    Processing and modification routes to produce and to improve properties of biodegradable plastics from soy isolate were studied. Soy isolate, acid-treated and crosslinked soy were subsequently compounded, extruded, and injection molded. Acetic acid and glyoxal were examined concerning their

  6. Decoration of Multi-walled Carbon Nanotubes by Metal ...

    African Journals Online (AJOL)

    The powder patterns of the as-prepared and acid treated MWCNTs are shown by the XRD spectra. The TEM results show the microstructure of the multi-walled carbon nanotubes well decorated with metal nanoparticles (Cu, Fe, Ni) and metal oxides (CuO, Fe2O3, NiO), while the SEM show the surface morphology.

  7. Eichhornia crassipes

    African Journals Online (AJOL)

    Zaranyika

    2015-10-26

    Oct 26, 2015 ... dilute mineral acid and organic solvent treatment resulted in a decrease in ... materials depend on the plant type from which they are .... Elemental analysis of untreated and acid treated biomass. Element ..... evolution of cell-wall architecture. ... The diverse applications of water hyacinth with main focus on.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (Peffects were not as marked......Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice....... 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...

  9. A comparison of oxolinic acid concentrations in farmed and laboratory held rainbow trout ( Oncorhynchus mykiss ) following oral therapy

    DEFF Research Database (Denmark)

    Coyne, R.; Samuelsen, O.; Kongshaug, H.

    2004-01-01

    Plasma oxolinic acid (OXA) concentrations were measured in fish from a cage of farmed rainbow trout (Oncorhynchus mykiss) 1 day after the termination of medication. The fish were experiencing significant mortalities and following a diagnosis of vibriosis, OXA had been orally administered at 50 mg....../kg for 6 days over a 9-day period. Samples from healthy fish (n=20), moribund (n=26) and dead fish (n=10) were analysed by HPLC. There was a dramatic difference in the OXA concentrations between healthy and moribund fish. In the moribund group, none of which showed signs of recent feeding, 85% of the fish...... laboratory held rainbow trout (O. mykiss) following the administration of OXA under similar conditions of salinity, temperature and dosing regimen. In these laboratory held fish, the mean plasma OXA concentration was 0.133±0.068 mg/l. The major difference between the distributions of OXA concentrations...

  10. The elimination, distribution, and metabolism of 14C-toxaphene in the pregnant rat

    International Nuclear Information System (INIS)

    Pollock, G.A.; Hillstrand, R.

    1982-01-01

    Pregnant Sprague-Dawley rats were orally administered 14 C-toxaphene in olive oil on day 15 of pregnancy and housed in glass metabolism cages. Urine, feces, and tissues were collected and assayed for radioactivity. The elimination was similar to that in virgin females with the majority of activity excreted in the feces (38.4%; five days) and less in the urine (23.7%; five days). The fetuses contained the lowest levels of radioactivity of all tissues tested (28 ppb; five days) and fat contained the highest levels (7476 ppb; five days). A comparison of the activity in the fetuses with that in the dam's fat showed slight differences, indicating the presence of more polar compounds (perhaps metabolites)

  11. The Level of SGOT and SGPT after The Administration of Powdered Colorant Pigment Isolated from Kesumba Keling’s (Bixa Orellana Seed Coats An experimental study in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    Suparmi Suparmi

    2011-06-01

    Design and Methods: The research is an experimental research with Factorial Design with 2 factors. Food Colorant Powder was made from bixin, norbixin, and crude extract pigment isolated from B. orellana seed coat’s. A total of 60 male mice were divided into 10 treatment groups. Powdered colorant solution at the concentration of 0% (control, 1%, 5%, and 10% were orally administered using gavage as much as 1 ml a day for 30 days. Results: Kruskal Wallis test results shows a not significant difference SGOT and SGPT level among the groups (p > 0.05, thus consumption of colorant powder of bixin, norbixin, and the crude extract with various concentrations did not affect the SGOT and SGPT. Conclusion: Colorant powder isolated from B. orellana seed coat’s has been shown to have no effect on the liver function, so it is safe as food colorant (Sains Medika, 3(1:69-77.

  12. Antigenotoxic potential of Asparagus racemosus root extract against electron beam radiation induced micronuclei formation in Swiss albino mice

    International Nuclear Information System (INIS)

    Bhandary, B. Satheesh Kumar; Sharmila, K.P.; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

    2016-01-01

    To evaluate the antigenotoxic potential of Asparagus Racemosus Root ethanolic extract (ARE) against electron beam radiation induced micronuclei formation in Swiss albino mice. Micronucleus assay was performed in the bone marrow of Swiss albino mice according to the method of Hosseinimehr et al., 2003. The experimental animals were orally administered 200 mg/kg body weight of ARE once daily for 15 consecutive days. At the end of experimental period, the animals were euthanized and the bone marrow was collected from the femur. Control (C), Radiation control (RC) and drug control (DC) group was also maintained. The number of radiation induced Micronucleated Polychromatic Erythrocytes (MnPCE) and Micronucleated Normochromatic Erythrocytes were decreased in the ARE treated mice which was statistically significant (p<0.05) compared to radiation control group. Present findings demonstrate the antigenotoxic potential of ARE against electron beam radiation induced micronuclei formation which may be attributed to scavenging of radiation-induced free radicals

  13. Colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai in patients with ulcerative colitis: a report of two cases.

    Science.gov (United States)

    Kondo, Satoru; Araki, Toshimitsu; Okita, Yoshiki; Yamamoto, Akira; Hamada, Yasuhiko; Katsurahara, Masaki; Horiki, Noriyuki; Nakamura, Misaki; Shimoyama, Takahiro; Yamamoto, Takayuki; Takei, Yoshiyuki; Kusunoki, Masato

    2018-03-16

    Orally administered Qing-dai, called indigo naturalis in Latin, is reportedly useful for the treatment of ulcerative colitis. We herein describe two patients with ulcerative colitis who developed colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai. In Case 1, a 35-year-old man developed colitis similar to ischemic colitis with bloody stool that recurred each time he ingested Qing-dai. He had no signs of recurrence upon withdrawal of Qing-dai. In Case 2, a 43-year-old woman underwent ileocecal resection for treatment of an intussusception 2 months after beginning oral administration of Qing-dai. Edema and congestion but no ulceration were present in the mucosa of the resected specimen. Both patients exhibited abdominal pain with bloody diarrhea, and abdominal computed tomography showed marked wall edema affecting an extensive portion of the large bowel.

  14. Garlic protects the glutathione redox cycle in irradiated rats

    International Nuclear Information System (INIS)

    Abu-Ghadeer, A.R.M.; Osman, S.A.A.; Abbady, M.M.

    1999-01-01

    The aim of the present study is to evaluate the possible radioprotective role of garlic oil on the glutathione redox cycle (GSH, GSH-Px, GR and G6-PD) in blood and tissues (liver, spleen and intestine) of irradiated rats. Garlic oil was orally administered to rats (100 mg/Kg- b.w.) for 7 days before exposure to a fractionated of whole body gamma irradiation up to 9 Gy (3 Gy X 3 at 2 days intervals) and during the whole period of irradiation. The data showed that radiation exposure caused significant inhibition of the biochemical parameters in blood and tissue of irradiated rats all over the investigation periods (3,7 and 15 days). Garlic oil ameliorated the decrease in the tested parameters with noticeable effect on the 15 Th. day after radiation exposure. It is concluded that garlic oil could control the radiation induced changes in the glutathione redox cycle and provided some radioprotective effect

  15. Thiolated chitosans: useful excipients for oral drug delivery.

    Science.gov (United States)

    Werle, Martin; Bernkop-Schnürch, Andreas

    2008-03-01

    To improve the bioavailability of orally administered drugs, formulations based on polymers are of great interest for pharmaceutical technologists. Thiolated chitosans are multifunctional polymers that exhibit improved mucoadhesive, cohesive and permeation-enhancing as well as efflux-pump-inhibitory properties. They can be synthesized by derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions. Various data gained in-vitro as well as in-vivo studies clearly demonstrate the potential of thiolated chitosans for oral drug delivery. Within the current review, the synthesis and characterization of thiolated chitosans so far developed is summarized. Features of thiolated chitosans important for oral drug delivery are discussed as well. Moreover, different formulation approaches, such as matrix tablets and micro-/nanoparticles, as well as the applicability of thiolated chitosans for the oral delivery of various substance classes including peptides and efflux pump substrates, are highlighted.

  16. Ameliorative Activity of Ethanolic Extract of Artocarpus heterophyllus Stem Bark on Alloxan-induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Basiru Olaitan Ajiboye

    2018-03-01

    Full Text Available Purpose: Diabetes mellitus is one of the major endocrine disorders, characterized by impaired insulin action and deficiency. Traditionally, Artocarpus heterophyllus stem bark has been reputably used in the management of diabetes mellitus and its complications. The present study evaluates the ameliorative activity of ethanol extract of Artocarpus heterophyllus stem bark in alloxan-induced diabetic rats. Methods: Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with 50, 100 and 150 mg/kg body weight ethanol extract of Artocarpus heterophyllus stem bark once daily for 21 days. Results: At the end of the intervention, diabetic control rats showed significant (p0.05 different with non-diabetic rats. Conclusion: The results suggest that ethanol extract of Artocarpus heterophyllus stem bark may be useful in ameliorating complications associated with diabetes mellitus patients.

  17. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-01-01

    Full Text Available Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days, or combined with acupuncture at Shenting (DU24, Tianzhu (BL10, Sishencong (Extra, Yintang (Extra, Renzhong (DU26, Neiguan (PC6, Shenmen (HT7, Fengchi (GB20, Wangu (GB12 and Baihui (DU20 (once a day for 56 days. Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia.

  18. Effects of oral contraceptive agents and sex steroids on carbohydrate metabolism.

    Science.gov (United States)

    Kalkhoff, R K

    1972-01-01

    The article offers a general interpretation of the influence of oral contraceptive agents on glucose tolerance, emphasizing comparisons of synthetic sex hormones. Although there are conflicting reports on steroid-induced diabetes in normal women, their glucose curves are often higher when under oral contraceptive treatment, suggesting that oral contraceptives may induce a form of subclinical diabetes melitus that is reversible. Evidence from diabetic women suggests definite deliterious effects from contraceptive administration. Estradiol, estriol, and estrone may improve glucose tolerance in nondiabetic women and reduce insulin requirements in diabetics. Progesterone has little effect on carbohydrate tolerance, as did synthetic progestin. Conjugated equine estrogens (equilenine or Premarin) may provoke mild to moderate deterioration of carbohydrate tolerance. Parenterally administered natural estrogens and orally administered synthetic derivatives appear to differ sharply in their effects. Sex hormones' effects on carbohydrate metabolism likely involve interactions with insulin and endogenous glucocorticoids.

  19. PROPAFENONE, A NEW EFFECTIVE ANTIARRHYTHMIC DRUG. REPORT OF 2 YEARS CLINICAL EXPERIMENT WITH PROPAFENONE (WITH BRIEF REVIEW OF ARTICLES

    Directory of Open Access Journals (Sweden)

    IRAJ NAZERY

    1986-05-01

    Full Text Available Propafenone HCI (p, is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics . Intravenously administered, (P was effective in 85% of patients with paroxysmal reentrant supraventricular tachycardia (PRSVT, 75% of those with paroxysmal atrial fibrillation (PAF , 50% and 42% of those with refractory premature ventricular contractions (PVC and ventricular tachycardia (V. Tach, respectively. Orally administered, (P was effective in 73% of those with resistant PVCs and nonsustained ventricular tachycardia (NSV Tach, and 75% of those with resistant sustained ventricular tachycardia (RSVT •

  20. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

    Science.gov (United States)

    Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

    2014-01-01

    Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

  1. Application of attenuated total reflectance Fourier transform infrared spectroscopy for determination of cefixime in oral pharmaceutical formulations.

    Science.gov (United States)

    Kandhro, Aftab A; Laghari, Abdul Hafeez; Mahesar, Sarfaraz A; Saleem, Rubina; Nelofar, Aisha; Khan, Salman Tariq; Sherazi, S T H

    2013-11-01

    A quick and reliable analytical method for the quantitative assessment of cefixime in orally administered pharmaceutical formulations is developed by using diamond cell attenuated total reflectance (ATR) Fourier transform infrared (FT-IR) spectroscopy as an easy procedure for quality control laboratories. The standards for calibration were prepared in aqueous medium ranging from 350 to 6000mg/kg. The calibration model was developed based on partial least square (PLS) using finger print region of FT-IR spectrum in the range from 1485 to 887cm(-1). Excellent coefficient of determination (R(2)) was achieved as high as 0.99976 with root mean square error of 44.8 for calibration. The application of diamond cell (smart accessory) ATR FT-IR proves a reliable determination of cefixime in pharmaceutical formulations to assess the quality of the final product. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Tratamento de candidiases muco-cutâneas rebeldes pelo Ketoconazol

    Directory of Open Access Journals (Sweden)

    Leila Dagher

    1983-11-01

    Full Text Available Results with orally administered ketoconazole in patients with mucocutaneous candidosis are encouraging, considering the recalcitrant nature of the disease. Thirty-two patients with mucocutaneous candidosis were treated with a dayle dose of 200 to 400mg of ketoconazole administered with a meal. Evaluation was based on clinical and parasitological responses. Clinical and parasitological cure was obtained in 28 (87,50% patients and improvement in 2(6,25%. No undesirable and effects were observed in the treatment.Experimentação terapêutico-laboratorial com o Ketoconazol nas candidíases mucocutâneas rebeldes, obtendo-se os seguintes resultados: - CURADOS: - 28 (87,50% pacientes; melhorados: - 2 (6,25% pacientes; inalterados: - 2 (6,25% pacientes. Laboratorialmente, houve negativação dos exames micológicos em 100% dos casos.

  3. Caloric utilization of sorbitol and isomalt in the rat

    International Nuclear Information System (INIS)

    Figdor, S.K.; Allingham, R.P.; Kita, D.A.; Hobbs, D.C.

    1987-01-01

    Sorbitol and isomalt are modified saccharides used to substitute for the physical properties of sucrose in various prepared foods. The merits of the various methods for determining caloric availability were reviewed. Balance and growth curve methods are inaccurate and inappropriate for determination of the caloric availability of these substances when present in diets at low concentrations, whereas the radiolabel disposition method is a direct and precise measure of utilization. Accordingly, the authors administered uniformly 14 C-labeled material to rats and collected excreta and expired air. The appearance of about half of the label in CO 2 indicated that, by comparison with labeled glucose, about 80% of the orally administered sorbitol and isomalt was calorically available to the rat. The high caloric availabilities of these materials were confirmed by the appearance in feces of only 14 and 12% of the administered label from sorbitol and isomalt, respectively

  4. Effect of diclofenac on the pharmacokinetics of moxifloxacin in rats.

    Science.gov (United States)

    Chen, L; Guo, S; Xu, M; Wu, L-X; Zhang, J-H

    2014-07-01

    A sensitive and specific method was developed and validated for the determination of moxifloxacin in plasma using HPLC. The effect of diclofenac (12.5, 25, 50 mg/kg) on the pharmacokinetics of orally administered moxifloxacin (40 mg/kg) in rats was investigated. Pharmacokinetic parameters of moxifloxacin were determined in rats following oral administration to rats in the presence and absence of diclofenac. The coadministration of the 2 drugs resulted in 10~29.5% decrease of the AUC and a 24.7~34% decrease of t1/2 for moxifloxacin; Tmax for moxifloxacin was 1.41~1.9-fold higher than that after the administration of moxifloxacin alone; Cmax for moxifloxacin decreased by 20.5~49%, as compared to that after the administration of moxifloxacin alone. Consequently, moxifloxacin and diclofenac should be monitored closely for potential drug interactions. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Even ‘safe’ medications need to be administered with care

    Science.gov (United States)

    Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

    2013-01-01

    A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even ‘Safe’ medications need to be carefully administered. PMID:23283606

  6. Even 'safe' medications need to be administered with care.

    Science.gov (United States)

    Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

    2013-01-02

    A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even 'Safe' medications need to be carefully administered.

  7. In Vitro Adsorption and in Vivo Pharmacokinetic Interaction between Doxycycline and Frequently Used Mycotoxin Binders in Broiler Chickens.

    Science.gov (United States)

    De Mil, Thomas; Devreese, Mathias; Broekaert, Nathan; Fraeyman, Sophie; De Backer, Patrick; Croubels, Siska

    2015-05-06

    Mycotoxin binders are readily mixed in feeds to prevent uptake of mycotoxins by the animal. Concerns were raised for nonspecific binding with orally administered veterinary drugs by the European Food Safety Authority in 2010. This paper describes the screening for in vitro adsorption of doxycycline-a broad-spectrum tetracycline antibiotic-to six different binders that were able to bind >75% of the doxycycline. Next, an in vivo pharmacokinetic interaction study of doxycycline with two of the binders, which demonstrated significant in vitro binding, was performed in broiler chickens using an oral bolus model. It was shown that two montmorillonite-based binders were able to lower the area under the plasma concentration-time curve of doxycycline by >60% compared to the control group. These results may indicate a possible risk for reduced efficacy of doxycycline when used concomitantly with montmorillonite-based mycotoxin binders.

  8. Influence of Mycotoxin Binders on the Oral Bioavailability of Doxycycline in Pigs.

    Science.gov (United States)

    De Mil, Thomas; Devreese, Mathias; De Saeger, Sarah; Eeckhout, Mia; De Backer, Patrick; Croubels, Siska

    2016-03-16

    Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the gastrointestinal tract of animals, making them unavailable for systemic absorption. The antimicrobial drug doxycycline (DOX) is often used in pigs and is administered through feed or drinking water; hence, DOX can come in contact with mycotoxin binders in the gastrointestinal tract. This paper describes the effect of four mycotoxin binders on the absorption of orally administered DOX in pigs. Two experiments were conducted: The first used a setup with bolus administration to fasted pigs at two different dosages of mycotoxin binder. In the second experiment, DOX and the binders were mixed in the feed at dosages recommended by the manufacturers (= field conditions). Interactions are possible between some of the mycotoxin binders dosed at 10 g/kg feed but not at 2 g/kg feed. When applying field conditions, no influences were seen on the plasma concentrations of DOX.

  9. Inhibitory effect of rose hip (Rosa canina L.) on melanogenesis in mouse melanoma cells and on pigmentation in brown guinea pigs.

    Science.gov (United States)

    Fujii, Takashi; Ikeda, Katsumi; Saito, Morio

    2011-01-01

    The compounds present in rose hips exerting an inhibitory action against melanogenesis in B16 mouse melanoma cells were investigated by dividing an aqueous extract of rose hips (RE) into four fractions. The 50% ethanol eluate from a DIAION HP-20 column significantly reduced the production of melanin and was mainly composed of procyanidin glycosides. We also found that this 50% ethanol eluate reduced the intracellular tyrosinase activity and also had a direct inhibitory effect on tyrosinase obtained as a protein mixture from the melanoma cell lysate. We also investigated the effect of orally administering RE on skin pigmentation in brown guinea pigs, and found that the pigmentation was inhibited together with the tyrosinase activity in the skin. These data collectively suggest that proanthocyanidins from RE inhibited melanogenesis in mouse melanoma cells and guinea pig skin, and could be useful as a skin-whitening agent when taken orally.

  10. Radioprotective effectiveness of Adeturone, incapsulated in liposomes

    International Nuclear Information System (INIS)

    Pantev, T.

    1990-01-01

    The radioprotective properties of Adeturone (S,2-aminoethyl isothiuronic adenosine-5-triphosphate), incapsulated in mono- and tricomponent lisosomes was studied. Intraperitoneal adminisration of the radioprotector by means of monocomponent liposomes from egg lecithins, as well as of the radioprotector alone shortly before (15-30 min) gamma irradiation of mice with 7.5 Gy (LD 100/30 ) provided high survival rate - accordingly 80% and 75%. Orally administered Adeturone incapsulated in tricomponent liposomes (dipalmitoil-DL-3-lecithin:cholesterine:stearilamine - 7:2:1) protected mice exposed to lethal X-irradiation (7.8 Gy, LD 90/30 ) for 0.5 to 4.5 hours. Adeturone, applied alone under these conditions 4.5 hours before irradiation, was ineffective. The results clearly demonstrated a prolonged radioprotective effect of Adeturone, administered per os as liposome suspension. 2 tabs., 17 refs

  11. Pharmacokinetics of amoxicillin after oral administration in recently weaned piglets with experimentally induced Escherichia coli subtype O149 : F4 diarrhea

    DEFF Research Database (Denmark)

    Jensen, G.M.; Lykkesfeldt, J.; Frydendahl, K.

    2004-01-01

    Objective-To measure the effect of Escherichia coli subtype 0149:F4-induced diarrhea on the pharmacokinetics of orally administered amoxicillin in affected piglets relative to that of uninfected piglets. Animals-22 healthy 4-week-old recently weaned Danish crossbred piglets. Procedure-12 piglets...... were orally inoculated through gastric intubation with 10(9) CFUs of an E coli 0149:F4 strain and responded by developing diarrhea 12 to 16 hours later. Piglets were dosed with amoxicillin trihydrate solution (20 mg/kg) by gastric intubation. A control group of 10 age-matched piglets without signs...... that the concentration of the antimicrobial at the site of infection reflects the systemic concentration, higher doses of amoxicillin in the treatment of piglets with E coli 0149:F4-induced diarrhea may be appropriate....

  12. Dynamic esophageal scintigraphy

    International Nuclear Information System (INIS)

    Reilley, J.J.; Malmud, L.S.; Fisher, R.S.; Applegate, G.; DeVegvar, M.L.

    1982-01-01

    Esophageal scintigraphy was developed in order to quantitatively evaluate esophageal transit in patients with a variety of esophageal disorders. The study is performed with orally administered technetium-99m sulfur colloid in water, using a gamma camera on-line to a digital computer. Esophageal transit is expressed as the percent emptying for each of the first 15-sec intervals for 10 min after an initial swallow and at 15-sec intervals after serial swallows. Esophageal transit is significantly decreased in patients with motor disorders of the esophagus, compared to normal controls. In patients with reflux esophagitis, esophageal transit was abnormal when the reflux disease was accompanied by abnormal motor function. The technique we describe is the first quantitative test of esophageal function; it is a useful, sensitive, scintigraphic technique for evaluation of esophageal transit

  13. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

    2014-01-01

    are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

  14. Gastroesophageal scintiscanning in a pediatric population: dosimetry

    International Nuclear Information System (INIS)

    Castronovo, F.P. Jr.

    1986-01-01

    The dosimetry associated with orally administered [/sup 99m/Tc]sulfur colloid for the diagnosis of gastroesophageal reflux has not been adequately described for the pediatric populations. Standard MIRD methodology was performed for the following: newborn, 1, 5, 10, and 15 yr old, and adult standard man. The critical organ for all pediatric groups was the lower large intestine with absorbed dose of 0.927, 0.380, 0.194, 0.120 and 0.0721 rad/100 microCi, respectively. For the adult the critical organ was the upper large intestine with an absorbed dose of 0.0518 rad/100 microCi. These data should be considered when administering [99mTc]sulfur colloid orally in a pediatric population

  15. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid.

    Science.gov (United States)

    Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

    2017-04-05

    Sea buckthorn ( Hippophae rhamnoides ) -derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

  16. Carbon tetrachloride treatment induces anorexia independently of hepatitis in rats.

    Science.gov (United States)

    Okamoto, T; Okabe, S

    2000-08-01

    Oxidative stress is involved in the development of anorexia. In the present study, we examined the possible involvement of anorexia in oxygen radical-induced hepatitis. A low dose of carbon tetrachloride (1 ml/kg of a 1:1 solution with olive oil) was orally administered to rats with and without food restriction. In rats with food restriction, carbon tetrachloride treatment induced hepatitis and reduced the body weight gain. In contrast, carbon tetrachloride treatment did not induce hepatitis in rats without food restriction, but the body weight was decreased. In these rats, the loss of body weight was accompanied by a decrease in food intake. The present results indicate that the administration of a low dose of carbon tetrachloride to rats without food restriction induced anorexia independently of hepatitis.

  17. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  18. Imaging MS in Toxicology: An Investigation of Juvenile Rat Nephrotoxicity Associated with Dabrafenib Administration

    Science.gov (United States)

    Groseclose, M. Reid; Laffan, Susan B.; Frazier, Kendall S.; Hughes-Earle, Angela; Castellino, Stephen

    2015-06-01

    As part of an investigative nephrotoxicity study, kidney tissues from juvenile rats orally administered dabrafenib at different age intervals between postnatal day (PND) 7 to 35 were investigated by MALDI and LDI imaging mass spectrometry (IMS) to determine the chemical composition of tubular deposits. In the youngest age group (PND 7-13), MALDI IMS demonstrated that a dabrafenib carboxylic acid metabolite was diffusely localized to the regions of tubular deposits (medulla and corticomedullary junction); however, no dabrafenib-related material was detected directly from the deposits. Rather, the LDI IMS analysis determined that the deposits were composed primarily of calcium phosphate. Based on these data, the dabrafenib associated nephrotoxicity, including the formation of tubular deposits, was determined to be age dependent. Furthermore, immature renal function was hypothesized to be responsible for the susceptibility of the youngest pups.

  19. Antinociceptive and free radical scavenging activities of Cocos nucifera L. (Palmae) husk fiber aqueous extract.

    Science.gov (United States)

    Alviano, Daniela S; Rodrigues, Karen F; Leitão, Suzana G; Rodrigues, Marcio L; Matheus, Maria Eline; Fernandes, Patrícia D; Antoniolli, Angelo R; Alviano, Celuta S

    2004-06-01

    In the current study, the analgesic and free radical scavenging properties of an aqueous extract from the husk fiber of Cocos nucifera L. (Palmae) were demonstrated by the use of in vivo and in vitro models. The orally administered Cocos nucifera aqueous extract (200 or 400 mg/kg) inhibited the acetic acid-induced writhing response in mice. Tail flick and hot plate assays demonstrated that treatment of animals with this plant extract at 200 mg/kg induced attenuation in the response to a heat stimulus. A LD(50) of 2.30 g/kg was obtained in acute toxicity tests. Topic treatment of rabbits with the Cocos nucifera extract indicated that it does not induce any significant dermic or ocular irritation. In vitro experiments using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) photometric assay demonstrated that this plant extract also possesses free radical scavenging properties.

  20. Differential Requirements for T Cells in Viruslike Particle- and Rotavirus-Induced Protective Immunity▿

    Science.gov (United States)

    Blutt, Sarah E.; Warfield, Kelly L.; Estes, Mary K.; Conner, Margaret E.

    2008-01-01

    Correlates of protection from rotavirus infection are controversial. We compared the roles of B and T lymphocytes in protective immunity induced either by intranasally administered nonreplicating viruslike particles or inactivated virus or by orally administered murine rotavirus. We found that protection induced by nonreplicating vaccines requires CD4+ T cells and CD40/CD40L. In contrast, T cells were not required for short-term protective immunity induced by infection, but both T-cell-dependent and -independent mechanisms contributed to long-term maintenance of protection. Our findings indicate that more than one marker of protective immunity exists and that these markers depend on the vaccine that is administered. PMID:18184712

  1. Cell-selective determination of trace elements in testis by SR-XRF analysis with nanoprobe

    International Nuclear Information System (INIS)

    Homma-Takeda, Shino; Nishimura, Yoshikazu; Watanabe, Yoshito; Yukawa, Masae; Ueno, Shunji; Terada, Yasuko

    2005-01-01

    Organotin compounds are widely used in industry and its environmental contamination by these compounds has recently become a concern. It is known that they act as endocrine disruptors but details of the dynamics of Sn in reproductive organs are still unknown. In the present study, we attempted to determine Sn in the testis of rats exposed to tributyltin chloride (TBTC) cell-selectively by synchrotron radiation X-ray florescence analysis with nanoprobe. TBTC was orally administered to rats at a dose of 45 μmol/kg per day for 3 days. One day later, Sn was detected in spermatozoa at the stage VIII seminiferous tubule, which are the final step of spermatogenesis in the testis. Sn levels in the microdissectioned seminiferous tubules determined by inductively coupled argon plasma-mass spectrometry were approximately equivalent to that in the testis. These data indicate that Sn accumulates in germ cells as well as in spermatozoa in a short period of TBTC exposure. (author)

  2. Effects of divalent amino acids on iron absorption

    International Nuclear Information System (INIS)

    Christensen, J.M.; Ghannam, M.; Ayres, J.W.

    1984-01-01

    Solutions of each of 10 amino acids or ascorbic acid were mixed with iron and orally administered to rats. Iron was absorbed to a statistically significantly greater extent when mixed with asparagine, glycine, serine, or ascorbic acid as compared with a control solution of iron. The largest effects were for asparagine and glycine, which also increased iron absorption to a significantly greater extent than did serine or ascorbic acid. No statistically significant increase in iron absorption occurred when any of the other amino acids was mixed with iron. The extent of iron absorption from each test solution, as measured by area under the concentration of iron-59 in the blood-time curve (r2 . 0.0002), and the initial rate of iron absorption for each test solution (r2 . 0.01) showed no correlation with the stability constant of the amino acid-iron complex

  3. Labelling aflatoxine-B1 by radioactive iodine

    International Nuclear Information System (INIS)

    Kim, Y.S.; Park, K.B.; Sung, H.K.; Ryu, Y.W.

    1977-01-01

    Labelling aflatoxines, the potential carcinogenic compounds, by radioactive iodine has been studied. The auflatoxine-B 1 , which is known to be the most abundant components of auflatoxines in the nature, was labelled by radioactive iodine-125 through an acid catalyst chloroamine-T procedure. The radiochemical yield was amounted to 63.6%. The chemical structure of the labelled product was proved to be 6-iodo 5-methoxy coumarine structure of auflatoxine-B 1 molecule by means of I.R. and N.M.R. spectroscopy. The labelled product was orally administered in a test animal (rat) and examined the accumulation of radioactivity in the body at the definite time interval. The accumulation of the radioactivity was pronounced at the blood and the liver. There was no indication of the decomposition of auflatoxine-B 1 - 125 I in the organs of the test animal. (author)

  4. Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides Ellis.

    Science.gov (United States)

    Yang, Quanjun; Wu, Bin; Shi, Yujing; Du, Xiaowei; Fan, Mingsong; Sun, Zhaolin; Cui, Xiaolan; Huang, Chenggang

    2012-01-01

    Bioassay-guided fractionation of extracts from Fructus Gardeniae led to analysis of its bioactive natural products. After infection by influenza virus strain A/FM/1/47-MA in vivo, antiviral activity of the extracts were investigated. The target fraction was orally administered to rats and blood was collected. High-performance liquid chromatography coupled with photo diode array detector and electrospray ion trap multiple-stage tandem mass spectrometry was applied to screen the compounds absorbed into the blood. A structural characterization based on the retention time, ultraviolet spectra, parent ions and fragmentation ions was performed. Thirteen compounds were confirmed or tentatively identified. This provides an accurate profile of the composition of bioactive compounds responsible for the anti-influenza properties.

  5. Sex hormone studies by radioimmunoassay in pregnant and non-pregnant women and in women treated with hormonal contraceptives

    International Nuclear Information System (INIS)

    Tafurt, C.A.

    1980-12-01

    Blood concentration profiles for follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, testosterone, estradiol, estriol, progesterone, cortisol and sex hormonebinding globulin throughout a menstrual cycle were derived from measurements by radioimmunoassay and related procedures on serial blood samples from 16 normal women as controls. Similar studies were then performed on 9 normal women receiving a low-dose oral contraceptive combination of D-norgestrel and ethynlestradiol. Further studies were performed on 9 out of 16 normal women in whom progestational contraception was carried out with orally administered lynestrenol or intramuscularly administered norethindrone enathate and on 12 normal pregnant women from the 28th to the 38th week of pregnancy. Additional studies embracing chorionic gonadotropin progesterone and 17-hydroxyprogesterone were performed on 10 normal pregnant women from the 6th to the 12th week of pregnancy. Detailed results are presented and their significance discussed

  6. Encapsulation Strategies of Bacteriophage (Felix O1) for Oral Therapeutic Application.

    Science.gov (United States)

    Islam, Golam S; Wang, Qi; Sabour, Parviz M

    2018-01-01

    Due to emerging antibiotic-resistant strains among the pathogens, a variety of strategies, including therapeutic application of bacteriophages, have been suggested as a possible alternative to antibiotics in food animal production. As pathogen-specific biocontrol agents, bacteriophages are being studied intensively. Primarily their applications in the food industry and animal production have been recognized in the USA and Europe, for pathogens including Salmonella, Campylobacter, Escherichia coli, and Listeria. However, the viability of orally administered phage may rapidly reduce under the harsh acidic conditions of the stomach, presence of enzymes and bile. It is evident that bacteriophages, intended for phage therapy by oral administration, require efficient protection from the acidic environment of the stomach and should remain active in the animal's gastrointestinal tract where pathogen colonizes. Encapsulation of phages by spray drying or extrusion methods can protect phages from the simulated hostile gut conditions and help controlled release of phages to the digestive system when appropriate formulation strategy is implemented.

  7. The Role of Everolimus in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Malek Meskawi

    2015-12-01

    Full Text Available Everolimus (RAD001 is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC. In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs. However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib, which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  8. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

    Directory of Open Access Journals (Sweden)

    Shigeru Nakamura

    2017-04-01

    Full Text Available Sea buckthorn (Hippophae rhamnoides–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1, a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

  9. Linaclotide: first global approval.

    Science.gov (United States)

    McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

    2012-11-12

    Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  10. A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers

    DEFF Research Database (Denmark)

    Wienberg, M; Glenthøj, Birte Yding; Jensen, K S

    2009-01-01

    processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally...... administered dose of 15 mg escitalopram (a highly selective serotonin reuptake inhibitor (SSRI)) or placebo, after which their PN, MMN and P300 amplitude were assessed. Similar to our initial study with 10 mg escitalopram, 15 mg escitalopram significantly increased MMN, while it did not affect P300 amplitude....... In contrast to our initial study, however, the currently higher dose of escitalopram did not increase PN. Results support the view that a broad range of increased serotonergic activity enhances MMN, while the relationship between serotonin and PN seems more complex. The current study does not support...

  11. Transcriptomic profiling of trichloroethylene exposure in male mouse liver

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2015-03-01

    Full Text Available Chronic Trichloroethylene (TCE exposure could induce hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE for 5 days. As a beginning step, we profiled gene expression alterations induced by the TCE in mouse livers. Here we describe in detail the experimental methods, quality controls, and other information associated with our data deposited into Gene Expression Omnibus (GEO under GSE58819. Our data provide useful information for gene expression responses to TCE in mouse liver.

  12. Role of 5-ALA in improving extent of tumour resection in patients with Glioblastoma Multiforme.

    Science.gov (United States)

    Waqas, Muhammad; Khan, Inamullah; Shamim, Muhammad Shahzad

    2017-10-01

    Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use of 5- ALA in improving the extent of resection when compared to white light microscopy. A systematic review on the topic had a similar conclusion. Few studies have also hinted on a high false negative rate with the use of this technique..

  13. Lacto-ghrestatin, a novel bovine milk-derived peptide, suppresses ghrelin secretion.

    Science.gov (United States)

    Aoki, Hayato; Nakato, Junya; Mizushige, Takafumi; Iwakura, Hiroshi; Sato, Masaru; Suzuki, Hideyuki; Kanamoto, Ryuhei; Ohinata, Kousaku

    2017-07-01

    Ghrelin, an endogenous peptide isolated from the stomach, is known to stimulate food intake after peripheral administration. We found that the enzymatic digest of β-lactoglobulin decreases ghrelin secretion from the ghrelin-producing cell line MGN3-1. The peptides present in the digest were comprehensively analyzed using the nanoLC-OrbitrapMS. Among them, we identified that the nonapeptide LIVTQTMKG, corresponding to β-lactoglobulin(1-9), suppresses ghrelin secretion from MGN3-1 cells. We named LIVTQTMKG 'lacto-ghrestatin'. We found that lacto-ghrestatin decreases intracellular cAMP levels and mRNA expression levels of ghrelin production-related genes in MGN3-1 cells. Orally administered lacto-ghrestatin decreases plasma ghrelin levels and food intake in fasted mice. Lacto-ghrestatin is the first food-derived peptide to suppress ghrelin secretion in vitro and in vivo. © 2017 Federation of European Biochemical Societies.

  14. The case for plant-made veterinary immunotherapeutics.

    Science.gov (United States)

    Topp, Edward; Irwin, Rebecca; McAllister, Tim; Lessard, Martin; Joensuu, Jussi J; Kolotilin, Igor; Conrad, Udo; Stöger, Eva; Mor, Tsafrir; Warzecha, Heribert; Hall, J Chris; McLean, Michael D; Cox, Eric; Devriendt, Bert; Potter, Andrew; Depicker, Ann; Virdi, Vikram; Holbrook, Larry; Doshi, Ketan; Dussault, Marike; Friendship, Robert; Yarosh, Oksana; Yoo, Han Sang; MacDonald, Jacqueline; Menassa, Rima

    2016-01-01

    The excessive use of antibiotics in food animal production has contributed to resistance in pathogenic bacteria, thereby triggering regulations and consumer demands to limit their use. Alternatives for disease control are therefore required that are cost-effective and compatible with intensive production. While vaccines are widely used and effective, they are available against a minority of animal diseases, and development of novel vaccines and other immunotherapeutics is therefore needed. Production of such proteins recombinantly in plants can provide products that are effective and safe, can be orally administered with minimal processing, and are easily scalable with a relatively low capital investment. The present report thus advocates the use of plants for producing vaccines and antibodies to protect farm animals from diseases that have thus far been managed with antibiotics; and highlights recent advances in product efficacy, competitiveness, and regulatory approval. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  15. Phosphatidylinositol-specific phospholipase C activity in Lactobacillus rhamnosus with capacity to translocate.

    Science.gov (United States)

    Rodriguez, A V; Baigorí, M D; Alvarez, S; Castro, G R; Oliver, G

    2001-10-16

    Phosphatidylinositol-specific phospholipase C (PI-PLC) activity was investigated in 25 different lactic acid bacteria (LAB) strains belonging to the genera Lactobacillus, Weisella, and Enterococcus. PI-PLC activity was detected in 44% of the strains studied in culture medium without carbon source. From the PI-PLC positive strains, Lactobacillus rhamnosus ATCC 7469 was selected for translocation studies. Healthy mice were orally administered with a daily dose of 2.0 x 10(9) of viable L. rhamnosus suspension. Viable bacteria were detected in liver and spleen of mice fed with LAB for 7 days. Bacterial colonies isolated from liver were biochemically characterized, and further subjected to randomly amplified polymorphic DNA. Amplification patterns of five strains displayed identical profiles to L. rhamnosus. PI-PLC activity was determined in the strains recovered from liver.

  16. Oral administration of insulin by means of liposomes in animal experiments

    International Nuclear Information System (INIS)

    Tragl, K.H.; Pohl, A.; Kinast, H.

    1979-01-01

    Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

  17. Lactobacillus helveticus-fermented milk improves learning and memory in mice.

    Science.gov (United States)

    Ohsawa, Kazuhito; Uchida, Naoto; Ohki, Kohji; Nakamura, Yasunori; Yokogoshi, Hidehiko

    2015-07-01

    To investigate the effects of Calpis sour milk whey, a Lactobacillus helveticus-fermented milk product, on learning and memory. We evaluated improvement in scopolamine-induced memory impairment using the spontaneous alternation behaviour test, a measure of short-term memory. We also evaluated learning and working memory in mice using the novel object recognition test, which does not involve primary reinforcement (food or electric shocks). A total of 195 male ddY mice were used in the spontaneous alternation behaviour test and 60 in the novel object recognition test. Forced orally administered Calpis sour milk whey powder (200 and 2000 mg/kg) significantly improved scopolamine-induced cognitive impairments (P memory (2000 mg/kg; P learning and memory in healthy human subjects; however, human clinical studies are necessary.

  18. Effects of barium sulfate as a contrast medium to enterocutaneous fistulas

    International Nuclear Information System (INIS)

    Pelster, F.W.; Reichelt, S.; Arndt, M.; Eising, E.G.

    1989-01-01

    Fistulation following thoracic and epigastric interventions are conservatively treated, as a rule, because of the high rate of complications expected from reoperation. With properly functioning anastomotic transit, insufficiencies usually undergo spontaneous healing, within four to six weeks. Enterocutaneous fistulae developed in 29 of 271 patients with intrathoracic oesophagastric or oesophagojejunal anastomosis. Syringeal ramification into pleural or abdominal cavities were eliminated by means of an absorbable contrast medium, before barium sulphate was orally administered to all patients. Thoracic fistulae were closed after 21.8 days on average, while 20.3 days was the average period required for closure of epigastric fistulae. Barium sulphate was found to stimulate fistular tissue granulation, so that obliteration of the fistular system occurred much sooner, as compared to conservative treatment. The patient's quality of life can thus be improved, and hospitalisation can be shortened. Neither locally delimited nor systemic complications were observed in any of the cases described. (author)

  19. Forty cases of gastrointestinal neurosis treated by acupunture.

    Science.gov (United States)

    Zhao, Yaping; Ding, Min; Wang, Yanjun

    2008-03-01

    To compare the therapeutic effect of acupuncture for gastrointestinal neurosis with that of oral remedy. Eighty cases were randomly divided into the following 2 groups. In the treatment group, acupuncture was given for one month at the main points of Zhongwan (CV 12), Zusanli (ST 36), Taichong (LR 3) and Shenmen (HT 7), with the auxiliary points selected according to TCM differentiation. In the control group, Domperidone was orally administered for one month. The total effective rate was 92.5% in the treatment group and 75.0% in the control group, with a significant difference between the 2 groups (chi2 = 4.423, P neurosis and with less toxic side effects.

  20. Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan

    2016-01-01

    Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios...... (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15......%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0...

  1. Effects of alcoholic beverage treatment on spatial learning and fear memory in mice.

    Science.gov (United States)

    Hashikawa-Hobara, Narumi; Mishima, Shuta; Nagase, Shotaro; Morita, Keishi; Otsuka, Ami; Hashikawa, Naoya

    2018-04-24

    Although chronic ethanol treatment is known to impair learning and memory, humans commonly consume a range of alcoholic beverages. However, the specific effects of some alcoholic beverages on behavioral performance are largely unknown. The present study compared the effects of a range of alcoholic beverages (plain ethanol solution, red wine, sake and whiskey; with a matched alcohol concentration of 10%) on learning and memory. 6-week-old C57BL6J mice were orally administered alcohol for 7 weeks. The results revealed that red wine treatment exhibited a trend toward improvement of spatial memory and advanced extinction of fear memory. Additionally, red wine treatment significantly increased mRNA levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptors in mice hippocampus. These results support previous reports that red wine has beneficial effects.

  2. A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

    DEFF Research Database (Denmark)

    Sigalet, David L; Kravarusic, Dragan; Butzner, Decker

    2013-01-01

    [± SD] age 15.3 ± 1.3 years) and 10 controls (10.3 ± 1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose⁄mannitol recovery; all......  BACKGROUND⁄/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release...... of the small intestine) with a disease activity index >150. Fasting and postprandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose⁄mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean...

  3. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    Science.gov (United States)

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  4. Non-invasive diagnosis of isolated chylopericardium using precordial pericardial imaging after oral administration of 131I-triolein

    International Nuclear Information System (INIS)

    Fujiseki, Yoshiki; Katsura, Tadahiko; Goto, Masakatsu; Kawanishi, Katsuyuki

    1982-01-01

    Chylopericardium is a rare disease and affects both sexes equally from neonate to adult. Usually, there are abnormal connections between the pericardial cavity and thoracic lymphatic systems. These connections are detected by (1) recovery of orally administered Sudan III from pericardial fluid, (2) evidence of radioactivity in the pericardial fluid by paracentesis after oral administration of 131 I-labeled triolein, and (3) lymphangiography. However, these method are technically difficult and invasive, thus sometimes dangerous for children. We employed precordial pericardial imaging after oral administration of 131 I-labeled triolein on a 9-year-old Japanese girl wth isolated chylopericardium before and after surgery. Abnormal connections and the back-ward flow to the pulmonary lymphatics were demonstrated by this method. This is an easy, non-invasive, reliable and safe method for detecting the abnormal connections of pericardial and lymphatic systems in children with chylopericardium. (author)

  5. Effect of irradation on liver and kidney functions in rat subjected to cadmium or mercury ingestion

    International Nuclear Information System (INIS)

    Refaie, F.M.; Maharem, T.M.; Yousri, R.M.; Omeran, M.F.; Abdel-Hamid, F.M.

    1993-01-01

    Male albino rats were orally administered a single dose of cadmium chloride or mercuric acetate 5-days before exposure to whole body gamma irradiation at the dose levels 3 and 6 Gy. The biochemical analyses were carried out 3-days post irradiation. The data revealed that radiation exposure and/or Cd or Hg treatment resulted in significant increase in serum aminotransferases (ALT and AST) while SALP and SCHE showed statistical significant decrease as compared with the control group. Gamma irradiation (3 and 6 Gy) induced no changes in serum levels of urea and creatinine while significant increase was observed when the animals were administered Cd or Hg 5-days before gamma-irradiation. Significant decrease in urea and creatinine clearance and TPR could be recorded due to radiation exposure. Level of serum protein was not affected in all animal groups over the experimentation period. 2 tab

  6. Combined effect of radiation and polytriu insecticide on the development of rat embryo

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Gabal, H A; Eid, F A; Gaber, S H [National Centre for Radiation Research Technology, Faculty of Science for Girls, Al-Azhar University. Cairo (Egypt)

    1987-12-31

    In the present study 9 groups of pregnant female rats were used. The 1st group served as the control. The 2nd and 3rd groups were orally administered polytrin insecticide:1/100 L D 50 on days 1 and 7 of gestation. Groups 4,5 and 6 were exposed to 2 Gy -rays on day 6, day 12 or days 6 and 12 of gestation. Groups 7,8 and 9 were exposed to 2 Gy gamma -ray on day 6, day 12 or days 6 and 12 during polytrin treatment. The results showed serious abnormal developmental changes as intrauterine death, gross malformations and relation when the embryos or fetuses were maternally exposed to -rays and/or treated with the pyrethroid compound. Moreover the malformations were higher and more drastic in the groups exposed to irradiation during polytrin treatment. These results are very important from the standpoint environmental pollution and radiation protection and safety. figs 23., 8 tabs.

  7. 125I-iomazenil binding shows stress- and/or diazepam-induced reductions in mouse brain. Supporting data for 123I-iomazenil SPECT study of anxiety disorders

    International Nuclear Information System (INIS)

    Takahashi, Makoto; Odano, Ikuo; Fujita, Shozo; Ohkubo, Masaki.

    1997-01-01

    Effects of repeated swim stress on the binding of 125 I-iomazenil were examined in the brains of diazepam-treated and non-treated mice. The mice were orally administered diazepam or vehicle (0.5% ethylene glycol) and subjected to daily swim stress (at 20degC for 10 min) for seven consecutive days. The distribution and the amount of 125 I-iomazenil binding were analyzed autoradiographically after in vivo and in vitro binding experiments. Repeated swim stress decreased the in vivo binding in the hippocampus (p 125 I-iomazenil binding. These results suggest that we can investigate the pathophysiology of stress and anxiety with 123 I-iomazenil SPECT. Care must be taken concerning the effects of benzodiazepines. (author)

  8. Chemotherapy for carcinoma of stomach

    International Nuclear Information System (INIS)

    Salek, T.

    2011-01-01

    Of all patients with gastric cancer 80 % to 90 % are either diagnosed at an advanced stage when the tumour is inoperable, or develop a recurrence within five years after surgery. Chemotherapy clearly improves survival in comparison to best supportive care only. No chemotherapy regimen showed a survival benefit better than 5-fluorouracil alone in a phase III trial for advanced gastric cancer in 1990s, and several new cytotoxic agents became available in late 1990s. Thereafter, a couple of phase III trials supported the substitution of infusional 5-fluorouracil by orally administered agents and the replacement of cisplatin by oxaliplatin in early 2000s. Trastuzumab has succeeded in showing a survival benefit for patients with Her-2 positive gastric cancer which accounts for about 10 - 20 % of the cancer. This means that the door is opened to the new era of chemotherapy with molecular target agents and with individualization for advanced gastric cancer. (author)

  9. Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

    Science.gov (United States)

    Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

    2017-05-01

    Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Oral Delivery of Curcumin Polymeric Nanoparticles Ameliorates CCl4-Induced Subacute Hepatotoxicity in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Gregory Marslin

    2018-05-01

    Full Text Available Curcumin is the major bioactive compound of Curcuma longa, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that curcumin nanoparticles (ηCur protects Wistar rats against carbon tetrachloride (CCl4-induced subacute hepatotoxicity. Nanoparticles of sizes less than 220 nm with spherical shape were prepared using PLGA and PVA respectively as polymer and stabilizer. Test animals were injected via intraperitoneal route with 1 mL/kg CCl4 (8% in olive oil twice a week over a period of 8 weeks to induce hepatotoxicity. On the days following the CCl4 injection, test animals were orally administered with either curcumin or its equivalent dose of ηCur. Behavioural observation, biochemical analysis of serum and histopathological examination of liver of the experimental animals indicated that ηCur offer significantly higher hepatoprotection compared to curcumin.

  11. Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

    Science.gov (United States)

    Maldonado-Gómez, María X; Martínez, Inés; Bottacini, Francesca; O'Callaghan, Amy; Ventura, Marco; van Sinderen, Douwe; Hillmann, Benjamin; Vangay, Pajau; Knights, Dan; Hutkins, Robert W; Walter, Jens

    2016-10-12

    Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Sofosbuvir treatment and hepatitis C virus infection

    Science.gov (United States)

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  13. Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei).

    Science.gov (United States)

    Wu, Yu-Sheng; Liau, Shu-Yu; Huang, Cheng-Ting; Nan, Fan-Hua

    2016-10-01

    This study mainly evaluated the effects of orally administered beta 1,3/1,6-glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever.

    Science.gov (United States)

    Gök, Kevser; Cengiz, Gizem; Erol, Kemal; Ozgocmen, Salih

    2017-01-01

    Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.

  15. Clinical Efficacy Comparison of Saccharomyces Boulardii and Lactic Acid as Probiotics in Acute Pediatric Diarrhea.

    Science.gov (United States)

    Asmat, Shakila; Shaukat, Fouzia; Asmat, Raheela; Bakhat, Hafiz Faiq Siddique Gul; Asmat, Tauseef M

    2018-03-01

    To compare the efficacy of Saccharomyces boulardii and lactic acid producing probiotics in addition to usual treatment regimen to cure diarrhea among children (6 months to 5 years of age). Randomized controlled trial. Department of Pediatrics, Sheikh Zayed Hospital, Lahore, from February to July 2015. Children suffering from acute diarrhea were orally administered Saccharomyces boulardii and lactic acid producing probiotics for 5 days. The efficacy of administered probiotics was monitored. Patients were given Saccharomyces boulardii and lactic acid producing probiotics randomly to remove the bias. Two hundred patients randomly selected for trials; out of which, 100 were treated with Saccharomyces boulardii while the other 100 were supplemented with lactic acid concomitantly along with conventional diarrhea treatment. Results indicated that Saccharomyces boulardii treatment group has significantly higher efficacy rate (45%) compared to lactic acid producing probiotics (26%). This study concluded that Saccharomyces boulardii has a better efficacy compared to lactic acid and may be adopted as a probiotic of choice.

  16. Expression and Regulation of Drug Transporters and Metabolizing Enzymes in the Human Gastrointestinal Tract.

    Science.gov (United States)

    Drozdzik, M; Oswald, S

    2016-01-01

    Orally administered drugs must pass through the intestinal wall and then through the liver before reaching systemic circulation. During this process drugs are subjected to different processes that may determine the therapeutic value. The intestinal barrier with active drug metabolizing enzymes and drug transporters in enterocytes plays an important role in the determination of drug bioavailability. Accumulating information demonstrates variable distribution of drug metabolizing enzymes and transporters along the human gastrointestinal tract (GI), that creates specific barrier characteristics in different segments of the GI. In this review, expression of drug metabolizing enzymes and transporters in the healthy and diseased human GI as well as their regulatory aspects: genetic, miRNA, DNA methylation are outlined. The knowledge of unique interplay between drug metabolizing enzymes and transporters in specific segments of the GI tract allows more precise definition of drug release sites within the GI in order to assure more complete bioavailability and prediction of drug interactions.

  17. The effects of crude aqueous and alcohol extracts of Aloe vera on growth and abdominal viscera of suckling rats.

    Science.gov (United States)

    Beya, Wabeya; Davidson, Bruce; Erlwanger, Kennedy H

    2012-01-01

    The gastrointestinal tract of neonates is sensitive to dietary manipulations. When nursing mothers use Aloe vera, their babies are at risk of indirect exposure to Aloe vera via breast feeding or directly as health supplements. The effects of orally administered extracts of Aloe vera in unweaned rats were investigated. Six day old Sprague-Dawley rats were gavaged with aqueous or alcohol extracts of Aloe vera (low dose 50mg. kg⁻¹ or high dose 500mg. kg⁻¹) daily for eight days. All data were expressed as mean ± SD and analyzed by one way ANOVA. Pups receiving high doses of either extract had a significantly higher body mass gain than the group receiving lower dose (p Aloe vera extracts resulted in growth promotion, enhanced hepatic storage of metabolic substrates, increased ALP possibly in relation to bone growth and caused hypertrophy of the caecum of neonatal rats. These effects need to be explored further to enhance animal production and health.

  18. 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......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

  19. An in vivo evaluation of induction of abnormal sperm morphology by ivermectin MSD (Mectizan).

    Science.gov (United States)

    Otubanjo, O A; Mosuro, A A; Ladipo, T F

    2007-01-01

    The in vivo effects of orally administered ivermectin (Mectizan) on sperm head morphology of albino mice were evaluated. Four different dose levels of 0.25, 0.5, 1.0 and 1.5 x the human therapeutic dose of 150 g kg(-1) body weight, were administered to the animals. The animals were exposed to a single oral treatment. The sperm of the mice from the cauda epididymes were examined 5 and 7 weeks after treatment. Ivermectin (Mectizan) induced sperm head abnormalities; however, the induction was not significantly elevated above the negative control value. Furthermore, the induction of the sperm head abnormalities was not strictly dose-dependent and there was also no correlation between dose level of administered drug and incidence of abnormal sperms. This indicates that the drug might not be mutagenic.

  20. An enzyme-linked immunosorbent assay for monoester-type aconitic alkaloids and its application in the pharmacokinetic study of benzoylhypaconine in rats.

    Science.gov (United States)

    Liu, Can-Can; Xu, Yun-Hui; Yuan, Shuai; Xu, Yu; Hua, Mo-Li

    2018-04-01

    A new enzyme-linked immunosorbent assay (ELISA) method for quantitative determination of monoester-type aconitic alkaloids was developed. The antibodies derived from the immunogen of benzoylmesaconine (BM) could be electively affined to benzoylaconitine-type alkaloids with an ester bond (14-benzoyl-), especially to benzoylhypaconine (BH, 140.02% of cross-reactivity). The effective working range of BH was 1 ng/ml to 5 μg/ml; the lower limit of detection and the quantification were 0.35 and 0.97 ng/ml, respectively. The values of CV for intra-day and inter-day assays and recovery ratios were in acceptable ranges. The results of stability experiments were also satisfactory. This validated method was employed for pharmacokinetic study of BH in rats and the bioavailability orally administered was estimated to be 16.3%.

  1. Oral cadmium chloride intoxication in mice: Effects of penicillamine, dimercaptosuccinic acid and related compounds

    International Nuclear Information System (INIS)

    Andersen, O.; Nielsen, J.B.

    1988-01-01

    The antidotal efficacies of chelators during acute cadmium intoxication has previously been examined in experiments where both a soluble cadmium salt and the chelator were administered parenterally. In the present study, PA, DMSA and related compounds were studied as oral antidotes during oral CdCl 2 intoxication. According to the antagonistic effects noted on mortality, peristaltic toxicity and intestinal cadmium uptake, the relative efficacies of the compounds tested were: DMSA>PAD>DMPS>MSA>PA>NAPA. None of the chelators induced major changes in the organ distribution of absorbed cadmium, in particular no increased cerebral deposition of cadmium. This study indicates that, in oral cadmium intoxication in humans, orally administered DMSA would be likely to offer protection against the local toxicity of cadmium in the gastrointestinal tract as well as to reduce the risk of systemic toxicity of absorbed cadmium. (author)

  2. Aloe vera (Aloe barbadensis Miller) supplemented probiotic lassi prevents Shigella infiltration from epithelial barrier into systemic blood flow in mice model.

    Science.gov (United States)

    Hussain, Shaik Abdul; Patil, Girdhari Ramdas; Reddi, Srinu; Yadav, Vidhu; Pothuraju, Ramesh; Singh, Ram Ran Bijoy; Kapila, Suman

    2017-01-01

    The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid. Blood was collected in heparinized tubes for various haematological studies. Oral administration of APL showed a significant (p Shigella counts (log cfu/mL) in all organs as compared to other treatment groups at different intervals after post feeding. Similarly, secretary IgA antibody levels (μg/mL) in intestinal fluid were significantly (p Shigella dysenteriae induced infection in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck

    2015-01-01

    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well......, studies of peptide and protein drug diffusion in and through mucus and studies of mucus-penetrating nanoparticles are included to illustrate the mucus as a potentially important barrier to obtain sufficient bioavailability of orally administered drugs, and thus an important parameter to address...

  4. Larvicidal activity of Bacillus thuringiensis var. israelensis Cry11Aa toxin against Haemonchus contortus.

    Science.gov (United States)

    DE Lara, Ana Paula DE Souza Stori; Lorenzon, Lucas Bigolin; Vianna, Ana Muñoz; Santos, Francisco Denis Souza; Pinto, Luciano Silva; Aires Berne, Maria Elisabeth; Leite, Fábio Pereira Leivas

    2016-10-01

    Effective control of gastrointestinal parasites is necessary in sheep production. The development of anthelmintics resistance is causing the available chemically based anthelmintics to become less effective. Biological control strategies present an alternative to this problem. In the current study, we tested the larvicidal effects of Bacillus thuringiensis var. israelensis Cry11Aa toxin against Haemonchus contortus larvae. Bacterial suspensions [2 × 108 colony-forming units (CFU) g-1 of the feces] of B. thuringiensis var. israelensis and recombinant Escherichia coli expressing Cry11Aa toxin were added to naturally H. contortus egg-contaminated feces. The larvae were quantified, and significant reductions of 62 and 81% (P var. israelensis and recombinant E. coli expressing Cry11Aa toxin were then orally administered to lambs naturally infected with H. contortus. Twelve hours after administration, feces were collected and submitted to coprocultures. Significant larvae reductions (P var. israelensis is a promising new class of biological anthelmintics for treating sheep against H. contortus.

  5. A Phase 1 biodistribution study of p-boronophenylalanine

    International Nuclear Information System (INIS)

    Coderre, J.A.

    1991-01-01

    The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed

  6. Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever

    Directory of Open Access Journals (Sweden)

    Kevser Gök

    2017-01-01

    Full Text Available Familial Mediterranean fever (FMF is the most common hereditary auto-inflammatory (periodic fever syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA. Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.

  7. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2016-01-01

    Full Text Available Dendrobium officinale (Tie Pi Shi Hu in Chinese has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

  8. Effect of the oral intake of probiotic Pediococcus acidilactici BA28 on Helicobacter pylori causing peptic ulcer in C57BL/6 mice models.

    Science.gov (United States)

    Kaur, Baljinder; Garg, Neena; Sachdev, Atul; Kumar, Balvir

    2014-01-01

    Probiotic lactic acid bacteria are being proposed to cure peptic ulcers by reducing colonization of Helicobacter pylori within the stomach mucosa and by eradicating already established infection. In lieu of that, in vitro inhibitory activity of pediocin-producing probiotic Pediococcus acidilactici BA28 was evaluated against H. pylori by growth inhibition assays. Further, chronic gastritis was first induced in two groups of C57BL/6 mice by orogastric inoculation with H. pylori with polyethylene catheter, and probiotic P. acidilactici BA28 was orally administered to study the eradication and cure of peptic ulcer disease. H. pylori and P. acidilactici BA28 were detected in gastric biopsy and fecal samples of mice, respectively. A probiotic treatment with P. acidilactici BA28, which is able to eliminate H. pylori infection and could reverse peptic ulcer disease, is being suggested as a co-adjustment with conventional antibiotic treatment. The study provided an evidence of controlling peptic ulcer disease, by diet mod

  9. Concentrated Phosphatidic Acid in Cereal Brans as Potential Protective Agents against Indomethacin-Induced Stomach Ulcer.

    Science.gov (United States)

    Afroz, Sheuli; Ikoma, Teru; Yagi, Ayano; Kogure, Kentaro; Tokumura, Akira; Tanaka, Tamotsu

    2016-09-21

    One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer.

  10. Mefloquine pharmacokinetics in healthy subjects and in peptic ulcer patients after cimetidine administration.

    Science.gov (United States)

    Kolawole, J A; Mustapha, A; Abudu-Aguye, I; Ochekpe, N

    2000-01-01

    The pharmacokinetics of orally administered mefloquine were determined in six healthy male subjects and in six ulcer patients before and after a 3-day course of cimetidine (400 mg morning and evening). Peak plasma concentrations Cmax and AUC0-infinity were similarly and significantly (P infinity was increased by 37.5% in healthy and peptic ulcer subjects respectively. The values of t1/2ab absorption and t1/2 beta elimination, total crearance CLT/F and volume of distribution were altered to varying levels after cimetidine treatment but the changes were not statistically significant in both healthy and peptic ulcer subjects. The established long t1/2 beta and this apparent interaction between mefloquine and cimetidine which resulted in increased mefloquine plasma concentration might be of clinical significant in patients with neurological/psychiatric history.

  11. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    International Nuclear Information System (INIS)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-01-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production

  12. Regional cerebral blood flow and the effects of nicardipine, a new cerebral vasodilator, in patients with neuropsychiatric symptoms

    International Nuclear Information System (INIS)

    Toyoda, Katsuhiro; Motomura, Naoyasu; Murata, Koen; Sakai, Toshiaki; Yoshioka, Michio; Tsutsumi, Shigetoshi.

    1984-01-01

    Regional cerebral blood flow (rCBF) was determined by 133 Xe inhalation method in 22 neuropsychiatric patients with an average age of 65.8 years -- 14 patients having cerebrovascular disturbance (Group 1) and 8 patients having endogenous or organic psychosis or neurological lesions (Group 2). Furthermore, nicardipine was orally administered to the patients and its effects on rCBF and on neuropsychiatric symptoms were examined. Regarding the mean and abnormal decrease of rCBF in the bilateral hemispheres and the frequency of ischemic foci, there was no significant difference between the groups. However, regional ischemic focus was more frequently observed in Group 1 than in Group 2. Long-term serial administration of nicardipine increased the rCBF and improved psychiatric symptoms in some of the patients in Group 1. (Namekawa, K.)

  13. Bacterial cell motility of Burkholderia gut symbiont is required to colonize the insect gut.

    Science.gov (United States)

    Lee, Jun Beom; Byeon, Jin Hee; Jang, Ho Am; Kim, Jiyeun Kate; Yoo, Jin Wook; Kikuchi, Yoshitomo; Lee, Bok Luel

    2015-09-14

    We generated a Burkholderia mutant, which is deficient of an N-acetylmuramyl-l-alanine amidase, AmiC, involved in peptidoglycan degradation. When non-motile ΔamiC mutant Burkholderia cells harboring chain form were orally administered to Riptortus insects, ΔamiC mutant cells were unable to establish symbiotic association. But, ΔamiC mutant complemented with amiC gene restored in vivo symbiotic association. ΔamiC mutant cultured in minimal medium restored their motility with single-celled morphology. When ΔamiC mutant cells harboring single-celled morphology were administered to the host insect, this mutant established normal symbiotic association, suggesting that bacterial motility is essential for the successful symbiosis between host insect and Burkholderia symbiont. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Neutron activation analysis of trace metals in the hair and organs of small animals treated chronically with Hg and Mn

    International Nuclear Information System (INIS)

    Ohmori, S.; Hashimoto, K.

    1985-01-01

    For the purpose of studying the secretion of exogenous toxic metals into hair, the relation between their concenrations in hair and in organs, and the metal shift Hg or Mn was orally administered to Guinea pigs for protracted periods. The distributions of metals in hair and organs were examined by means of neutron activation analysis. It was found that the administration of Hg at high dose resulted in abnormally high Hg levels in hair from the 2nd dosing week and in organs after 25 weeks of dosing, and in a reduced motor activity after 25 weeks of administration. There occurred metal shifts in hair as well. Administration of Mn at high doses, on the other hand, showed no such biological influences, although a dose-dependent increase of Mn in hair was detected with time. (author)

  15. BDDCS Applied to Over 900 Drugs

    DEFF Research Database (Denmark)

    Benet, Leslie Z.; Broccatelli, Fabio; Oprea, Tudor

    2011-01-01

    and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N = 53 compared with over 200 each in classes 1–3). The influence of several measured and in silico parameters in the process of BDDCS category assignment......Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513......) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD 7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number...

  16. Effect of massive administration of cepharanthin on leukopenia in radio- and chemotherapy

    International Nuclear Information System (INIS)

    Otani, Katsumi

    1975-01-01

    Cepharanthin was given to the patients with cancer who received radio- and chemotherapy, and the blood findings were examined. Subjects were 30 patients of 19 patients with cancer of the cervix of the uterus, 5 with ovarian cancer and 6 with choriepithelioma. Sixty mg. of cepharanthin was orally administered every day at the same time when the therapy was initiated, and the blood findings were obserbed. When the therapy was completed, the decrease rate of leukocyte count was less than 20% in 23 patients (76.6%), showing an obvious recovery of leukocyte count at the termination of the therapy. Blood platelet count decreased to less than 5x10 4 in only 2 patients, and it was nothing but a temporary decrease. Although a little variation was found in the values of red blood cell, hemoglobin, hematocrit, GOT and GPT, the variation was considered to remain in normal range. There was no severe side effect caused by cepharanthin. (Kanao, N.)

  17. Effect of Garlic, Gingko, and St. John's Wort Extracts on the Pharmacokinetics of Fexofenadine: A Mechanistic Study.

    Science.gov (United States)

    Turkanovic, Jasmina; Ward, Michael B; Gerber, Jacobus P; Milne, Robert W

    2017-05-01

    The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW; 1000 mg/kg; positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines divided into four segments (SI-SIV) and analyzed for P-gp and Oatp1a5. In vivo, SJW increased the clearance of i.v. administered fexofenadine by 28%. Garlic increased the area under the curve 0-∞ and maximum plasma concentration of orally administered fexofenadine by 47% and 85%, respectively. Ginkgo and SJW had no effect on the oral absorption of fexofenadine. In the perfused liver, garlic, ginkgo, and SJW increased the biliary clearance of fexofenadine with respect to perfusate by 71%, 121%, and 234%, respectively. SJW increased the biliary clearance relative to the liver concentration by 64%. The ratio of liver to perfusate concentrations significantly increased in all treated groups. The expression of Oatp1a5 in SI was increased by garlic (88%) and SJW (63%). There were no significant changes in the expression of P-gp. Induction of intestinal Oatp1a5 by garlic may explain the increased absorption of orally administered fexofenadine. Ginkgo had no effect on the expression of intestinal P-gp or Oatp1a5. A dual inductive effect by SJW on opposing intestinal epithelial transport by Oatp1a5 and P-gp remains a possibility. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Stabilization of the Serum Lithium Concentration by Regulation of Sodium Chloride Intake: Case Report.

    Science.gov (United States)

    Tomita, Takashi; Goto, Hidekazu; Sumiya, Kenji; Yoshida, Tadashi; Tanaka, Katsuya; Kohda, Yukinao

    2016-01-01

    To avoid fluctuation of the serum lithium concentration (CLi), sodium chloride (NaCl) intake was regulated in oral alimentation. A 62-year-old woman was hospitalized and orally administered 400 mg of lithium carbonate a day to treat her mania. Her CLi was found to be 0.75-0.81 mEq/L. Vomiting made it difficult for the patient to ingest meals orally, and therefore parenteral nutrition with additional oral intake of protein-fortified food was initiated. On day 22, parenteral nutrition was switched to oral alimentation to enable oral intake of food. The total NaCl equivalent amount was decreased to 1.2 g/d, and the CLi increased to 1.15 mEq/L on day 26. Oral alimentation with semi-solid food blended in a mixer was immediately initiated. Although the total NaCl equivalent amount was increased to 4.5-5.0 g/d, her CLi remained high at 1.14-1.17 mEq/L on days 33 and 49, respectively. We investigated oral administration of NaCl (1.8 g/d) on day 52. The total NaCl equivalent amount was increased to 6.3-6.8 g/d, and the CLi decreased to 1.08-0.97 mEq/L on days 63 and 104, respectively. After the start of the orally administered NaCl, her diet was changed to a completely blended diet on day 125. The total NaCl equivalent amount was increased to 9.0-14.5 g/d, and the CLi decreased to 0.53 mEq/L on day 152; therefore, the oral administration of NaCl was discontinued on day 166. The CLi was found to be 0.70-0.85 mEq/L on days 176 and 220.

  19. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mandiwana, Vusani, E-mail: VMandiwana@csir.co.za; Kalombo, Lonji, E-mail: LKalombo@csir.co.za [Centre of Polymers and Composites, CSIR (South Africa); Venter, Kobus, E-mail: Kobus.Venter@mrc.ac.za [South African Medical Research Council (South Africa); Sathekge, Mike, E-mail: Mike.Sathekge@up.ac.za [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine (South Africa); Grobler, Anne, E-mail: Anne.Grobler@nwu.ac.za; Zeevaart, Jan Rijn, E-mail: zeevaart@necsa.co.za [North-West University, DST/NWU Preclinical Drug Development Platform (South Africa)

    2015-09-15

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([{sup 153}Sm]Sm{sub 2}O{sub 3}) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive {sup 153}Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The {sup 153}Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [{sup 153}Sm]Sm{sub 2}O{sub 3} loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [{sup 153}Sm]Sm{sub 2}O{sub 3}-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  20. Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice.

    Science.gov (United States)

    Yoneda, Mitsugu; Sugimoto, Naotoshi; Katakura, Masanori; Matsuzaki, Kentaro; Tanigami, Hayate; Yachie, Akihiro; Ohno-Shosaku, Takako; Shido, Osamu

    2017-01-01

    Theobromine, which is a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. Theobromine works as a phosphodiesterase (PDE) inhibitor to increase intracellular cyclic adenosine monophosphate (cAMP). cAMP activates the cAMP-response element-binding protein (CREB), which is involved in a large variety of brain processes, including the induction of the brain-derived neurotrophic factor (BDNF). BDNF supports cell survival and neuronal functions, including learning and memory. Thus, cAMP/CREB/BDNF pathways play an important role in learning and memory. Here, we investigated whether orally administered theobromine could act as a PDE inhibitor centrally and affect cAMP/CREB/BDNF pathways and learning behavior in mice. The mice were divided into two groups. The control group (CN) was fed a normal diet, whereas the theobromine group (TB) was fed a diet supplemented with 0.05% theobromine for 30 days. We measured the levels of theobromine, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), phosphorylated CREB (p-CREB), and BDNF in the brain. p-VASP was used as an index of cAMP increases. Moreover, we analyzed the performance of the mice on a three-lever motor learning task. Theobromine was detectable in the brains of TB mice. The brain levels of p-VASP, p-CREB, and BDNF were higher in the TB mice compared with those in the CN mice. In addition, the TB mice performed better on the three-lever task than the CN mice did. These results strongly suggested that orally administered theobromine acted as a PDE inhibitor in the brain, and it augmented the cAMP/CREB/BDNF pathways and motor learning in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

    Science.gov (United States)

    Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

  2. Randomized, open-label, 5-way crossover study to evaluate the pharmacokinetic/pharmacodynamic interaction between furosemide and the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen in healthy volunteers.

    Science.gov (United States)

    Paterson, C A; Jacobs, D; Rasmussen, S; Youngberg, S P; McGuinness, N

    2011-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce renal complications in patients taking loop diuretics. This study investigated the pharmacokinetic/pharmacodynamic effects and safety profile of orally administered diclofenac sodium, ibuprofen and diclofenac epolamine topical patch (DETP) on furosemide in healthy adult subjects. This open-label, randomized, 5-way crossover study was conducted in 40 subjects (aged 19 - 45 y). Diclofenac (75 mg taken orally twice daily), DETP (1.3% applied topically twice daily), or ibuprofen (800 mg taken orally thrice daily) was administered for 3 consecutive days, followed by co-administration with furosemide (given intravenously as 20 mg/2 min). Plasma furosemide and NSAID concentrations, urine furosemide, sodium and potassium concentrations and urine output were determined throughout the 24 h period following furosemide administration. Orally administered ibuprofen significantly increased furosemide AUC(0-t) (37%) and AUC(0-inf) (36%) and decreased total body CL (27%), R(max) (19%) and CLR (23%) geometric mean ratios compared with furosemide control. Oral and topical diclofenac had no pharmacokinetic effects on furosemide. Ibuprofen increased sodium excretion (Ae(0-24), 16%) and decreased sodium R(max) (15%), and oral diclofenac decreased urine output (Vu(0-24), 15%). DETP had no effect on furosemide pharmacodynamics; total systemic exposure to diclofenac during DETP treatment was diclofenac. Treatments were generally safe, with 25 subjects reporting a total of 112 adverse events. Pharmacodynamic effects were seen with oral diclofenac (urine output) and ibuprofen (urine sodium excretion). Furosemide also affected plasma and urine pharmacokinetic profiles. Pharmacologic effects of DETP on furosemide were not observed under these conditions. Additional research is warranted to delineate the potential interactions of other NSAIDs with furosemide and other loop diuretics.

  3. Oral delivery of capsaicin using MPEG-PCL nanoparticles.

    Science.gov (United States)

    Peng, Wei; Jiang, Xin-yi; Zhu, Yuan; Omari-Siaw, E; Deng, Wen-wen; Yu, Jiang-nan; Xu, Xi-ming; Zhang, Wei-ming

    2015-01-01

    To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality. CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining. CAP/NPs had an average diameter of 82.54 ± 0.51 nm, high drug-loading capacity of 14.0% ± 0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation. CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.

  4. Distribution Dynamics of Recombinant Lactobacillus in the Gastrointestinal Tract of Neonatal Rats

    Science.gov (United States)

    Bao, Sujin; Zhu, Libin; Zhuang, Qiang; Wang, Lucia; Xu, Pin-Xian; Itoh, Keiji; Holzman, Ian R.; Lin, Jing

    2013-01-01

    One approach to deliver therapeutic agents, especially proteins, to the gastro-intestinal (GI) tract is to use commensal bacteria as a carrier. Genus Lactobacillus is an attractive candidate for use in this approach. However, a system for expressing exogenous proteins at a high level has been lacking in Lactobacillus. Moreover, it will be necessary to introduce the recombinant Lactobacillus into the GI tract, ideally by oral administration. Whether orally administered Lactobacillus can reach and reside in the GI tract has not been explored in neonates. In this study, we have examined these issues in neonatal rats. To achieve a high level of protein expression in Lactobacillus, we tested the impact of three promoters and two backbones on protein expression levels using mRFP1, a red fluorescent protein, as a reporter. We found that a combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei with a backbone from pLEM415 yielded the highest level of reporter expression. When this construct was used to transform Lactobacillus casei, Lactobacillus delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in all these species and colonies of transformed Lactobacillus appeared pink under visible light. To test whether orally administered Lactobacillus can be retained in the GI tract of neonates, we fed the recombinant Lactobacillus casei to neonatal rats. We found that about 3% of the bacteria were retained in the GI tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus in the stomach and small intestine than in the cecum and colon. No mortality was observed throughout this study with Lactobacillus. In contrast, all neonatal rats died within 24 hours after fed with transformed E. coli. Taken together, our results indicate that Lactobacillus has the potential to be used as a vehicle for the delivery of therapeutic agents to neonates. PMID:23544119

  5. Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a systematic review.

    Science.gov (United States)

    Burow, E; Simoneit, C; Tenhagen, B-A; Käsbohrer, A

    2014-03-01

    Administration of antimicrobials to livestock increases the risk of antimicrobial resistance (AMR) in commensal bacteria. Antimicrobials in pig production are usually administered per pen via feed which implies treatment of sick alongside with healthy animals. The objective of this systematic literature review was to investigate the effect of orally administered antimicrobials on AMR in Escherichia coli of swine. Studies published in peer reviewed journals were retrieved from the international online databases ISI Web of Knowledge, PubMed, Scopus and the national electronic literature data base of Deutsches Institut für Medizinische Dokumentation und Information. The studies were assessed using the eligibility criteria English or German language, access to full paper version, defined treatment and control group (initial value or non-treatment) as well as administration and resistance testing of the same antimicrobial class. In the qualitative synthesis, only studies were included presenting the summary measures odds ratio or prevalence of resistance, the category of the applied antimicrobial and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as an "increase", "no effect" or "decrease" if the odds or alternatively the prevalence ratio were >1.0, 1.0 or antimicrobial substance and dosage was missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials were inhomogenous in usage and provision of information on sample size. Oral administration of antimicrobials increases the risk of AMR in E. coli from swine. There is however a lack of studies on the impact of dosage and longitudinal effects of treatment. The published studies have a number of issues concerning their scientific quality. More high quality research is needed to better address and quantifiy the effect of orally administered antimicrobials on AMR in swine. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Impact of high-flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy.

    Science.gov (United States)

    Hui, Katrina; Patel, Kashyap; Kong, David C M; Kirkpatrick, Carl M J

    2017-07-01

    Clearance of small molecules such as amoxicillin and clavulanic acid is expected to increase during high-flux haemodialysis, which may result in lower concentrations and thus reduced efficacy. To date, clearance of amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely unexplored. Using published pharmacokinetic parameters, a two-compartment model with first-order input was simulated to investigate the impact of high-flux haemodialysis on the probability of target attainment (PTA) of orally administered AMC combination therapy. The following pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For amoxicillin, the time that the free concentration remains above the minimum inhibitory concentration (MIC) of ≥50% of the dosing period (≥50%ƒT >MIC ) was used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of ≥45% of the dosing period (≥45%ƒT >0.1 mg/L ) was used. Dialysis clearance reported in low-flux haemodialysis for both compounds was doubled to represent the likely clearance during high-flux haemodialysis. Monte Carlo simulations were performed to produce concentration-time profiles over 10 days in 1000 virtual patients. Seven different regimens commonly seen in clinical practice were explored. When AMC was dosed twice daily, the PTA was mostly ≥90% for both compounds regardless of when haemodialysis commenced. When administered once daily, the PTA was 20-30% for clavulanic acid and ≥90% for amoxicillin. The simulations suggest that once-daily orally administered AMC in patients receiving high-flux haemodialysis may result in insufficient concentrations of clavulanic acid to effectively treat infections, especially on days when haemodialysis occurs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  7. 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 (Penrofloxacin, 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.

  8. Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated linoleic acid (9Z11E-18:2) in rats.

    Science.gov (United States)

    Tsuzuki, Tsuyoshi; Tokuyama, Yoshiko; Igarashi, Miki; Nakagawa, Kiyotaka; Ohsaki, Yusuke; Komai, Michio; Miyazawa, Teruo

    2004-10-01

    We previously showed that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is converted to conjugated linoleic acid (CLA; 9,11-18:2) in the liver and plasma of rats that were given diets including 1% alpha-ESA for 4 wk. In this study, we investigated this phenomenon in detail. First, the chemical structure of CLA produced by alpha-ESA administration was determined. After alpha-ESA was orally administered to rats, CLA in rat liver was isolated by HPLC. The positional and geometric isomerism was determined using GC-EI/MS and (13)C-NMR, respectively, and the CLA generated in rats after alpha-ESA feeding was confirmed to be 9Z11E-CLA. Next, the concentrations of alpha-ESA and CLA were determined 0, 3, 6, and 24 h after oral administration of alpha-ESA to rats. Moreover, we also investigated whether enteric bacteria are involved in the conversion of alpha-ESA to CLA using germ-free rats. alpha-ESA was orally administered to germ-free and normal rats and alpha-ESA and CLA were detected in the organs of both groups. In addition, to confirm that this reaction was enzyme-mediated, alpha-ESA was reacted with tissue homogenates (liver, kidney, and small intestine mucous) and coenzymes (NADH, NAD(+), NADPH, and NADP(+)), and the enzyme activities were estimated from the amount of CLA produced. CLA was detected when alpha-ESA was reacted with liver, kidney, and small intestine mucous homogenates and a coenzyme (NADPH). These results indicated that alpha-ESA is converted to 9Z11E-CLA in rats by a Delta13-saturation reaction carried out by an NADPH-dependent enzyme.

  9. Gastrointestinal drug absorption in rats exposed to 60Co γ-radiation

    International Nuclear Information System (INIS)

    Brady, M.E.

    1976-01-01

    Following exposure of the gastrointestinal (GI) tract to ionizing radiation, its structure and function are altered for several days. Such alterations may affect the bioavailability of orally administered drugs. The potential mechanisms by which radiation may affect drug absorption were explored by studying the absorption of four test drugs, sulfanilamide, bretylium, sulfisoxazole acetyl, and riboflavin, in rats that were exposed to 850 R cobalt-60 gamma-radiation or sham irradiated. In one series of experiments, the drugs were administered orally and the amount of drug excreted in urine was used as a measure of the extent of their absorption. Cumulative urinary excretion of the drugs was shown to be a valid measure of absorption since it was not affected by radiation after intravenous administration of the drugs. At one day post-irradiation, the extent of absorption of sulfanilamide and bretylium was not affected by radiation but the absorption of sulfisoxazole acetyl and riboflavin was increased. At five days post-irradiation, there was no detectable difference between irradiated and control animals in the extent of absorption of the drugs. The fraction of sulfanilamide excreted in the urine as 4 N-conjugate was increased at one day post-irradiation. The increased excretion of metabolite appeared to result from metabolism of the drug by gut flora prior to absorption. This study shows that radiation-induced alterations in the absorption of orally administered drugs are due primarily to slowed gastric emptying. In general, slowed gastric emptying causes the rate of drug absorption to decline. The extent of absorption of drugs that are normally well absorbed is not affected by radiation while the extent of absorption of drugs that normally are absorbed poorly may be increased after irradiation of the GI tract

  10. No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

    Science.gov (United States)

    de la Peña, Amparo; Cui, Xuewei; Geiser, Jeanne; Loghin, Corina

    2017-11-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen ® were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.5 mg. The effect of dulaglutide coadministration was assessed based on the PK parameters of key analytes. For warfarin PD, the effect of dulaglutide on the international normalized ratio (INR) was evaluated. Areas under the concentration-time curves (AUCs) with and without dulaglutide were similar for all analytes except atorvastatin, where it was reduced by 21%. Maximum concentrations (C max ) were generally lower following coadministration with dulaglutide, with statistically significant reductions (90% confidence intervals of geometric least squares means ratios outside 0.80-1.25) for all analytes except R-warfarin. For all analytes, there was a general trend for the time to C max (t max ) to increase following coadministration with dulaglutide. For warfarin, dulaglutide coadministration had no statistically significant effect on the maximum INR (INR max ); however, a 2% increase in area under the INR curve (AUC INR ) was observed. Dulaglutide did not affect the absorption of the tested medications to a clinically relevant degree. Based on the PK and PD evaluations, no dose adjustments for digoxin, warfarin, atorvastatin and Ortho-Cyclen ® are recommended when coadministered with dulaglutide. NCT01458210, NCT01436201, NCT01432938, and NCT01250834.

  11. Absorption, tissue distribution, excretion, and metabolism of clothianidin in rats.

    Science.gov (United States)

    Yokota, Tokunori; Mikata, Kazuki; Nagasaki, Hiromi; Ohta, Kazunari

    2003-11-19

    Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.

  12. Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea pigs.

    Science.gov (United States)

    Sun, Y; Kiraly, A J; Sun, A R; Cox, M; Mauerhan, D R; Hanley, E N

    2018-02-01

    The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate 'analogue', Carolinas Molecule-01 (CM-01). Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs. In addition to cartilage degeneration, osteophytes, subchondral bone advance, and BMLs increased with age. Subchondral bone advance was observed as early as six months, whereas BMLs and osteophytes were both observed mainly at 12 and 18 months. Fibrotic BMLs were found mostly underneath the degenerated cartilage on the medial side. In contrast, necrotic BMLs were found almost exclusively in the interspinous region. Orally administered CM-01 decreased all of these pathological changes and reduced the levels of MMP13 expression. Subchondral bone may play a role in cartilage degeneration. Subchondral bone changes are early events; formation of osteophytes and BMLs are later events in the OA disease process. Carolinas Molecule-01 is a promising small molecule candidate to be tested as an oral disease-modifying drug for human OA therapy. Cite this article : Y. Sun, A. J. Kiraly, A. R. Sun, M. Cox, D. R. Mauerhan, E. N. Hanley Jr. Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea

  13. Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice.

    Science.gov (United States)

    Rhee, Ki-Jong; Lee, Chang Gun; Kim, Sung Woo; Gim, Dong-Hyeon; Kim, Hyun-Cheol; Jung, Bae Dong

    2015-01-01

    Diabetes mellitus (DM) is caused by either destruction of pancreatic β-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1β and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.

  14. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  15. Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

    Directory of Open Access Journals (Sweden)

    Soraya S Andrade

    2006-11-01

    Full Text Available Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%, followed by Klebsiella spp. (7%, Proteus mirabilis (6.4%, Enterococcus spp. (5.6%, and Pseudomonas aeruginosa (4.6%. Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%, TMP/SMX (40.4%, ciprofloxacin (21.6%, and gatifloxacin (17.1%. Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively, and P. mirabilis (71.8 and 84.6%, respectively. For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

  16. The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system.

    Science.gov (United States)

    Zhang, Lin; Chang, Jin-hua; Zhang, Bao-qi; Liu, Xi-gang; Liu, Pei; Xue, He-fei; Liu, Li-yan; Fu, Qiang; Zhu, Meng; Liu, Cui-zhe

    2015-07-01

    Rhubarb is commonly used as laxatives in Asian countries, of which anthraquinones are the major active ingredients, but there are an increased number of concerns regarding the nephrotoxicity of anthraquinones. In this study, we compared the pharmacokinetic characteristics of rhubarb anthraquinones in rats after orally administered with rhubarb and rhubarb total free anthraquinone oral colon-specific drug delivery granules (RTFA-OCDD-GN), and then explained why these granules could reduce the nephrotoxicity of anthraquinones when they produced purgative efficacy. A sensitive and reliable high performance liquid chromatography (HPLC) method has been fully validated for simultaneous determination of the five active components of rhubarb, and successfully applied to investigate and compare the remarkable differences in pharmacokinetic study of rhubarb anthraquinones after orally administered with rhubarb and RTFA-OCDD-GN. The results showed that, compared with rhubarb group, the AUC, Cmax, t1/2z and Vz/F of aloe-emodin, rhein, emodin and chrysophanol in rats receiving the RTFA-OCDD-GN were significantly decreased, and the Tmax of the four analytes was prolonged. Moreover, the Tmax of rhein, the Cmax of chrysophanol and emodin all have significant differences (Panthraquinone prototype excretion rates in urine and feces of aloe-emodin, rhein, emodin, chrysophanol and physcion were all increased. These findings suggested that oral colon-specific drug delivery technology made anthraquinone aglycone to colon-specific release after oral administration. This allowed anthraquinones to not only play the corresponding purgative effect but also avoid intestinal absorption and promote excretion. And thereby greatly reduced the nephrotoxicity of rhubarb. The result is a new breakthrough in rhubarb toxicity attenuated research. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Effect of oral coadministration of drugs on the disposition of (14C)-celiprolol HCl in rats

    International Nuclear Information System (INIS)

    Town, C.; Knipe, J.; Taft, C.; Tantillo, N.; Klunk, L.; Grebow, P.

    1986-01-01

    Celiprolol HCL (C) is a cardioselective β-blocker undergoing clinical trials as an antihypertensive agent. Studies with rats indicated that the oral coadministration of 2.5 mg/kg of chlorthalidone (CT) caused a 40% decrease in the urinary excretion of radioactivity from a 40 mg/kg dose of ( 14 C)-C(C). In order to further understand the nature of this interaction, groups of 6 rats were given 40 mg/kg of (C) alone and, one week later,/sub R.(C) pluse the drug to be tested. The vehicle was 0.5% Methocel. After each dosing, urine was collected for 96 hours from each rat and the amount of total radioactivity excreted was compared between treatments. The results showed that oral coadministration of 2.5 mg/kg hydrochlorothiazide, 2.5 mg/kg furosemide, 2.5 mg/kg indapamide, 5.0 mg/kg cimetidine, 10.0 mg/kg theophylline, and 1.0 mg/kg digoxin were without effect on the disposition of orally administered (C). Conversely, 2.5 mg/kg CT, 2.5 mg/kg acetazolamide (AZ) and 5.0 mg/kg hydralazine (H) caused a significant (p < 0.05) decrease in the urinary excretio of orally administered (C). CT and AZ are both potent inhibitors of carbonic anhydrase and their action on this enzyme may cause the effect on the disposition of (C). The action of H may be due to its pharmacologic action and warrants further study

  18. Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.

    Science.gov (United States)

    Reinero, Carol R; Decile, Kendra C; Byerly, Jenni R; Berghaus, Roy D; Walby, William E; Berghaus, Londa J; Hyde, Dallas M; Schelegle, Edward S; Gershwin, Laurel J

    2005-07-01

    To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma. 6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA). A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs. Mean +/- SE eosinophil percentages in BALF when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/- 1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%), compared with values for the control treatment (63.6 +/- 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments. Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGA-specific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma.

  19. High Purity Silica Production from Rice Husk Ash

    International Nuclear Information System (INIS)

    Yaminn Lwin; April Nwayy Nwayy Htett

    2010-12-01

    In this research, two types of raw material source, rice husk and rice husk ash, were used. Among the rice husk samples, taungpyan sample was chosen because it contains the maximum silica content and treated with (1,3,5) wt% sulphuric acid (96% concentration) and citric acid (99% concentration). These acid treated taungpyan samples and nonacid treated taungpyan sample were burned at 900C for 30 min. For rice husk ash samples, ash samples from fluidized combustor, fluidized gasifier and brick factory were collected. All of the rice husk ash samples were purified by alkaline extraction method with (2-3) N NaOH solution and followed by acid precipitation method with 5 N H2SO4 solution. According to the analysis and characterization, acid treated taungpyan sample (5 wt% citric acid) with the highest silica content (99.906 wt% and crystallization form) was obtained.

  20. Intermediate Temperature Fuel Cell Using Gypsum Based Electrolyte And Electrodes

    International Nuclear Information System (INIS)

    Suzuki, Satoshi; Nagai, Masayuki; Katagiri, Yuji

    2011-01-01

    The proton conductive electrolyte membrane and the electrodes for intermediate temperature fuel cell were made from the phosphoric acid treated gypsum as a proton conductor. The membrane and the electrodes were built into single cell and tested at intermediate temperature region. The power density of the fuel cell was 0.56 mW/cm -2 at 150 deg. C without any humidification and 1.38 mW/cm -2 at 150 deg. C, 5% relative humidity. The open circuit voltage of the cell was increased higher than 0.7 V when the electrodes were annealed at 150 deg. C, 5%R.H., however the reasons for this are still to be further investigated. The results show that the potential of the phosphoric acid treated gypsum for the intermediate temperature proton conductor.