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Sample records for multiple oral administration

  1. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  2. Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

    Science.gov (United States)

    Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

    2015-06-01

    Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

  3. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

    Science.gov (United States)

    Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

    2008-01-01

    To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

  4. Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

    Science.gov (United States)

    Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

    2015-01-01

    Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  6. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

    Science.gov (United States)

    Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

    2015-07-01

    To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

  8. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

    2017-05-15

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

  9. [Oral treatments in multiple sclerosis].

    Science.gov (United States)

    Meca-Lallana, José Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

    2014-12-01

    The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    Science.gov (United States)

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  11. Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

    Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  12. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

    Science.gov (United States)

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

    2016-12-24

    Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

  13. Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice

    International Nuclear Information System (INIS)

    Ikebe, E; Kawaguchi, A; Tezuka, K; Taguchi, S; Hirose, S; Matsumoto, T; Mitsui, T; Senba, K; Nishizono, A; Hori, M; Hasegawa, H; Yamada, Y; Ueno, T; Tanaka, Y; Sawa, H; Hall, W; Minami, Y; Jeang, K T; Ogata, M; Morishita, K; Hasegawa, H; Fujisawa, J; Iha, H

    2013-01-01

    In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression

  14. Nickel Excretion in Urine after Oral Administration

    DEFF Research Database (Denmark)

    Menne, T.; Mikkelsen, H. I.; Solgaard, Per Bent

    1978-01-01

    In recent years the importance of internal exposure to nickel in patients with recurrent hand eczema and nickel allergy has become evident. The present study was performed in order to investigate the value of urinary nickel determinations as an index of oral nickel intake. After oral administration...

  15. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  16. Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Menghua Liu

    2015-03-01

    Full Text Available Radix Astragali (RA is one of the commonly-used traditional Chinese medicines (TCMs with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.

  17. Pharmacokinetics difference of multiple active constituents from decoction and maceration of Fuzi Xiexin Tang after oral administration in rat by UPLC-MS/MS.

    Science.gov (United States)

    Zhang, Qian; Ma, Yue-ming; Wang, Zheng-tao; Wang, Chang-hong

    2014-04-01

    Fuzi Xiexin Tang (FXT) is a classic traditional Chinese medicine formula which has been employed in clinical for more than 1800 years. The distinctive preparation method (maceration) recorded in ancient time is different from one in modern clinical practice (decoction). Aim of this study is to investigate the pharmacokinetic difference of alkaloids, flavones and anthraquinones in rats after oral administration of decoction of FXT (DFXT, 30gkg(-1)), maceration of FXT (MFXT, 30gkg(-1)) and decoction of Aconiti Lateralis Radix Preparata (DAR, 6gkg(-1)) by a validated UPLC-MS/MS method. Plasma concentrations and pharmacokinetic parameters of 16 active constituents (aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, berberine, palmatine, jatrorrhizine, coptisine, baicalin, wogonin, wogonoside, emodin, aloe-emodin, rhein) in rat were quantified and compared. Different preparative methods resulted in significant difference on exposure and pharmacokinetic characteristics of alkaloids, flavones and anthraquinones from FXT, especially protoberberine alkaloids. Concentrations of monoester-diterpenoid alkaloids were below the LOD in rat plasma after administration of DFXT and MFXT because of the existence of other three herbs from FXT. Maceration could decrease the absorption of flavones while increased the absorption of anthraquinones. Cmax of emodin and rhein were 3.1 and 10.3 times increased, while eliminations of these two constituents were 8.0 and 19.0 times slower after administration of MFXT. Bioavailability of both flavones and anthraquinones increased after administration of MFXT, especially emodin and rhein increasing as much as 13.5 and 20.7 times. Herb-herb interaction between DAR and other three herbs from FXT significantly influenced the exposure of aconitum alkaloids. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. 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.

  19. Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

    Science.gov (United States)

    Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

    2014-04-01

    Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    Science.gov (United States)

    Chen, Xiaocheng; Cao, Gang; Jiang, Jianping

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat plasma after oral administration of crude C. officinals and its jiuzhipin. Results: The morroniside and loganin in crude and processed C. officinals could be simultaneously determined within 7.4 min. Linear calibration curves were obtained over the concentration ranges of 45.45-4800 ng/mL for all the analytes. The intra-and inter-day precisions relative standard deviation was lesser than 2.84% and 4.12%, respectively. Conclusion: The pharmacokinetic parameters of two iridoid glucosides were also compared systematically between crude and processed C. officinals. This paper provides the theoretical proofs for further explaining the processing mechanism of Traditional Chinese Medicines. PMID:24914290

  1. effect of oral administration of aqueous extract of cassia occidentalis

    African Journals Online (AJOL)

    DR. AMINU

    seeds extract's relation with acid – base balance of the body. Serum concentrations ... Oral administration of aqueous extract of C. occidentalis ... irrespective of duration of administration (weeks). .... Student 't' test was used to analyse the data.

  2. HTO oral administration in mice: Pt. 1

    International Nuclear Information System (INIS)

    Yamamoto, O.; Yokoro, K.; Seyama, T.; Kinomura, A.; Nomura, T.

    1990-01-01

    Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F 1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. Within a range of 1.48 x 10 11 to 5.92 x 10 11 Bq/dm 3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10 10 Bq/dm 3 and 1.48 x 10 11 Bq/dm 3 . At concentrations lower than 9.25 x 10 9 Bq/dm 3 , mice no longer died from haematopoietic failure. The authors conclude, therefore, that there should be a threshold dose rate for haematopoietic death. (author)

  3. Oral iron administration in suckling piglets – a review

    Directory of Open Access Journals (Sweden)

    Martin Svoboda

    2018-01-01

    Full Text Available Iron deficiency is presently a serious problem in suckling piglets on pig farms. The most often used method of anaemia prevention in piglets is parenteral administration of iron dextran. Oral iron represents an alternative to this method. The goal of this article is to review current knowledge on oral iron administration in suckling piglets. The substances that can be used for this purpose include iron dextran, iron salts, iron chelates, carbonyl iron, an iron polymaltose complex and iron microparticles. The different methods of oral iron administration in piglets are discussed.

  4. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  5. Effects of sub acute oral administration of aqueous extract of ...

    African Journals Online (AJOL)

    The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

  6. Repeated oral administration of capsaicin increases anxiety-like ...

    Indian Academy of Sciences (India)

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy ...

  7. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  8. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

    OpenAIRE

    Ke Yang; Shi-Wei Chen; Xin-Yan Dou; Zhi-Rui Zhang; Xin Jin; Hong-Min Zhang

    2018-01-01

    AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total). The c...

  9. Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

    African Journals Online (AJOL)

    This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

  10. Anti-tumour immune effect of oral administration of Lactobacillus

    Indian Academy of Sciences (India)

    Our results indicated that oral administration with L. plantarum inhibited CT26 cell ... (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. ... College of Animal Science and Technology, Jilin Agricultural University, ...

  11. Oral administration of Rauwolfia vomitoria extract has no untoward ...

    African Journals Online (AJOL)

    The effect of ethanolic extract of leaf and root of Rauwolfia vomitoria on kidney and liver functions in rats was investigated. Rats were given daily oral administration of ethanolic extracts of either root or leaf of R. vomitoria at two different concentrations (1.0 and 2.0 g/kg body weight) for a period of 14 days. Some biochemical ...

  12. Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

    Science.gov (United States)

    Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2012-10-01

    Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

  13. Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

    Science.gov (United States)

    Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

    2017-10-01

    OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

  14. The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

    Science.gov (United States)

    Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

    2016-09-01

    The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. © 2016 John Wiley & Sons Ltd.

  15. Reducing radiation exposure during oral I-131 therapy administration

    International Nuclear Information System (INIS)

    Trujillo, J.; Krinsky, S.; Wilson, B.; Teague, E.

    1982-01-01

    A new, closed-system method to reduce air-, direct-, and incidental-contamination during therapeutic administration of oral I-131 was experimentally evaluated on twelve patients. We studied a standard control population using the routine practice of drinking the solution through a straw and compared results with our new technique. Various measurements were performed throughout all phases of dose administration to assess the relative difference of the two approaches. Using the closed system method before and during iodine administration revealed between 100 and 1000 times less activity per millimeter of air sample; whereas, the direct radiation exposure values were higher for the control population. Both the experimental and control methods had similar levels of incidental contamination

  16. Oral administration of Allium sativum extract protects against infectious bursal disease in chickens

    Directory of Open Access Journals (Sweden)

    Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

    2015-12-01

    Full Text Available Garlic (Allium sativum, Liliaceae has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The in vivo effects of oral administration of garlic mixture (GM, water-soluble extract on infectious bursal disease virus (IBDV-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg-1 BW GM (Group GM1 on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 (P<0.01, suggesting that the oral administration of 5 mg·kg-1 GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed, demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

  17. Safety of 8-weeks oral administration of Arctium lappa L.

    Science.gov (United States)

    Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik; Park, Dae-Hun; Park, Kyung-Mok

    2017-09-01

    Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa . We concluded that treatment with lappa , which was within the safety range, resulted in body weight decrease and blood glucose suppression.

  18. Can dentists detect multiple myeloma through oral manifestations?

    Directory of Open Access Journals (Sweden)

    Thaís Miranda Xavier de Almeida

    2018-01-01

    Full Text Available Objective: To review published data on oral manifestations of multiple myeloma. Methods: An electronic database search was performed of articles published from 1971 to November 2016 in order to identify studies that reported oral manifestations of patients with multiple myeloma. Case reports and case series with oral manifestations of multiple myeloma in English were included in the study. An additional search was performed of the references of the selected articles. Results: Thirty-seven articles that reported 81 patients with oral manifestations of multiple myeloma were selected: 30 case reports (82% and seven case series (18%. The most common clinical features in the dental cavity were swelling (65.4%, bone pain (33.3%, paresthesia (27.1% and amyloidosis lesions (11.1%. Osteolytic lesions detected on imaging exams were reported in the majority of the patients (90.1% as plasmacytomas or ‘punched-out’ lesions. Conclusions: Swelling and osteolytic lesions represent the most common clinical and radiographic signs of the jaws relating to multiple myeloma, respectively. Keywords: Multiple Myeloma, Oral Manifestations, Mouth, Jaws

  19. A study of the treatment of oral multiple primary cancers

    International Nuclear Information System (INIS)

    Sato, Takayuki; Kamata, Shin-etsu; Kawabata, Kazuyoshi

    2003-01-01

    The subjects were 30 multiple primary cancers (out of 2,169 oral squamous cell carcinoma including lip cancers), which were treated at the Division of Head and Neck, Cancer Institute Hospital. Seven synchronous carcinomas and 23 metachronous cases were seen. The most common site of the primary cancer was the tongue. Surgical treatment was performed for the first treatment in 5 cases of the 7 synchronous cancers. On the other hand, radical treatment was performed in 11 cases of the 23 metachronous cancers. Fourteen of the 18 cases were treated by surgical treatment and controlled. It is suggested that surgical treatment is the most effective for oral multiple primary cancers. (author)

  20. Pharmacokinetics of Mequindox and Its Marker Residue 1,4-Bisdesoxymequindox in Swine Following Multiple Oral Gavage and Intramuscular Administration : An Experimental Study Coupled with Population Physiologically Based Pharmacokinetic Modeling

    NARCIS (Netherlands)

    Zeng, Dongping; Lin, Zhoumeng; Fang, Binghu; Li, Miao; Gehring, Ronette; Riviere, Jim E; Zeng, Zhenling

    2017-01-01

    Mequindox (MEQ) is a quinoxaline-N,N-dioxide antibiotic used in food-producing animals. MEQ residue in animal-derived foods is a food safety concern. The tissue distribution of MEQ and its marker residue 1,4-bisdesoxymequindox (M1) were determined in swine following oral gavage or intramuscular

  1. Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

    2017-03-01

    Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

  2. Multiple Hamartoma Syndrome with Characteristic Oral and Cutaneous Manifestations

    Directory of Open Access Journals (Sweden)

    Prashanthi Chippagiri

    2013-01-01

    Full Text Available Aim. To present a case of Cowden's syndrome and emphasize the importance of continued cancer surveillance in these patients. Cowden syndrome is an inherited autosomal dominant trait with incomplete penetrance and a range of expressivity. It is characterized by multiple hamartomas and neoplasms. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here, we report a case of Cowdens syndrome of a 30-year-old female patient who came with a complaint of multiple growths in the oral cavity of a three-month duration. On examination, multiple skin-colored, flat-topped papules over her forehead and right malar bone and multiple papillomatous papules involving all the mucosal surfaces intraorally were observed. This syndrome is associated with the development of several types of malignancies, especially breast carcinoma and thyroid carcinoma, which is why early recognition and regular and vigilant surveillance of individuals with the syndrome are important.

  3. Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

    Science.gov (United States)

    Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

    2010-01-01

    To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

  4. Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Benson, D; Arthur, R M

    2016-08-01

    Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

  5. Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

    Science.gov (United States)

    Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

    2013-10-01

    The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

  6. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

    Directory of Open Access Journals (Sweden)

    Ke Yang

    2018-04-01

    Full Text Available AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total. The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software(DAS2.1.1. RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88, 210.02±25.66, 188.83±31.74, 112.24±11.70, 90.28±22.01 and 57.67±13.71μg/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17±19.29, 97.95±10.49, 71.18±18.70, 39.11±2.44, 18.10±2.34 and 9.08±2.04μg/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min(PCONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.

  7. Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

    2015-04-01

    To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

  8. Administrative Challenges to the Integration of Oral Health With Primary Care

    Science.gov (United States)

    Maxey, Hannah L.; Randolph, Courtney; Gano, Laura; Kochhar, Komal

    2017-01-01

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce. PMID:27218701

  9. Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

    Science.gov (United States)

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  10. The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

    OpenAIRE

    Green, A R; Aronson, J K; Cowen, P J

    1985-01-01

    The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

  11. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2011-04-01

    The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed. Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  12. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

    Science.gov (United States)

    Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

    2017-11-01

    Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

  13. Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

    Science.gov (United States)

    Siden, Rivka; Wolf, Matthew

    2013-06-01

    The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

  14. Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam.

    Science.gov (United States)

    Zheng, Yong-Qiu; Wei, Wei; Shen, Yu-Xian; Dai, Min; Liu, Li-Hua

    2004-11-01

    To investigate the curative effects of oral and nasal administration of chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions. AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CII (20 microg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CII (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the

  15. Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars

    2016-01-01

    BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. OBJECTIVE: To evaluate the effect of monthly oral...... methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. METHODS: In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin...... no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. CONCLUSION: Monthly methylprednisolone pulse treatment was safe, but had...

  16. An improved technique for oral administration of solutions of test ...

    African Journals Online (AJOL)

    Medicut intravenous cannula as an improvised oral cannula to administer solutions of drugs and test substances to experimental rats. Techniques of handling and manipulating the rat with the goal of having the eosophagus as straight as possible ...

  17. Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

    Science.gov (United States)

    Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

    2012-02-01

    To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

  18. Multiple mucous retention cysts of the oral mucosa.

    Science.gov (United States)

    Tal, H; Altini, M; Lemmer, J

    1984-12-01

    While mucoceles of the oral mucosa are relatively common, multiple mucous retention cysts have not previously been reported. In this article two such cases, in which numerous minor salivary gland ducts had dilated to the point of cyst formation, are described. The number of individual cysts exceeded 100 in each case. Since it is clear that these cysts formed as a result of dilatation of salivary ducts, it would seem that either the ducts were blocked by altered secretion or there was an acquired or congenital weakness in their structure.

  19. Tissue distribution of berberine and its metabolites after oral administration in rats.

    Directory of Open Access Journals (Sweden)

    Xiang-Shan Tan

    Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

  20. Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

    DEFF Research Database (Denmark)

    Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

    2016-01-01

    Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

  1. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration...... serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... in the circulation for a substantially shorter time (24h serum concentration for IV and SC were 40ngh/mL and 30ngh/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption...

  2. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    Science.gov (United States)

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

  3. Managing the oral side-effects of medications used to treat multiple sclerosis.

    Science.gov (United States)

    Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

    2017-09-01

    Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

  4. Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

    Science.gov (United States)

    Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

    2018-01-01

    Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

  5. Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

    Science.gov (United States)

    Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

    2016-06-01

    There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

  6. Administrative support of novice science teachers: A multiple case study

    Science.gov (United States)

    Iacuone, Leann

    Novice science teachers leave the confines of colleges and universities to embark on a new adventure in education where they aim to influence young minds, make a difference in the world, and share their love for their content. They have learned their pedagogical skills with the support and assistance of fellow classmates, a supporting professor, and a cooperating teacher. These teachers enter their new place of employment and are met with many unexpected challenges, such as a lack of resources, no one to ask questions of, and a busy staff with already established relationships, causing them to feel an overall lack of support and resulting in many new teachers rethinking their career choice and leaving the field of education within 5 years of entering. This multiple-case study investigated the administrative support 4 novice science teachers received during an academic year and the novice teachers' perceptions of the support they received to answer the following research question: How do novice science teachers who have consistent interactions with administrators develop during their first year? To answer this question, semistructured interviews, reflection journals, observations, resumes, long-range plans, and student discipline referrals were collected. The findings from this study show novice science teachers who had incidents occur in the classroom requiring administrative assistance and guidance felt more confident in enforcing their classroom management policies and procedures as the year progressed to change student behavior. The novice science teachers perceived administrators who provided resources including technology, office supplies, science supplies, and the guidance of a mentor as supportive. Novice science teachers who engaged in dialogue after administrative observations, were provided the opportunity to attend professional development outside the district, and had a mentor who taught the same discipline made more changes to their instructional

  7. Prevention of urogenital infections by oral administration of probiotic lactobacilli

    Directory of Open Access Journals (Sweden)

    Vedran Slačanac

    2010-09-01

    Full Text Available In general, lactobacilli are nonpathogenic part of the normal urogenital microflora and have been recognized as a barrier against colonization of unwanted (pathogen microflora. The results of many in vitro studies suggest following mechanisms of probiotic lactobacilli action in urogenital tract: adhesion to urogenital cells, competition with pathogens for adhesive sites, production of biosurfactants, co-aggregation with pathogens, production of antimicrobial substances (organic acids, hydrogen peroxide and bacteriocins and stimulation of immune system. From 80 different lactobacilli species isolated from human or animal intestinal and urogenital tract, only few lactobacilli strains possess optimal properties to be effective as probiotic therapeutics against infections in the urogenital tract. Combination of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 was proposed as the best one for epithelial vaginal cells colonization and inhibition of uropathogens adhesion. The results of a number of clinical studies confirmed beneficial role of oral lactobacilli. However, the most of commercially available Lactobacillus strains, which are ordinary used in fermented dairy products,are seriously limited in protection of urogenital tract when they are ingested orally.

  8. Effects of oral administration of Phyllanthus amarus leaf extract on ...

    African Journals Online (AJOL)

    The histological findings indicated that the treated sections of the kidneys showed hypertrophy of blood vessels, mild-severe infiltrate of chronic inflammatory cells and varying degrees of tubular necrosis when compared to the control sections. The findings indicated that the administration of Phyllanthus amarus extract has ...

  9. 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.

  10. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    Science.gov (United States)

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  11. Eliminating the need for fasting with oral administration of bisphosphonates

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

    2013-01-01

    or beverages create complexes that cannot be absorbed. For this reason, they must be taken on an empty stomach, and a period of up to 2 hours must elapse before the consumption of any food or drink other than plain water. This routine is not only inconvenient but can lead to discontinuation of treatment......Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates) and when taken with food......, and when mistakenly taken with food, may result in misdiagnosis of resistance to or failure of treatment. The development of an enteric-coated delayed-release formulation of risedronate with the addition of the calcium chelator, ethylenediaminetetraacetic acid (EDTA), a widely used food stabilizer...

  12. Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

    DEFF Research Database (Denmark)

    Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

    2002-01-01

    The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

  13. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  14. Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

    Science.gov (United States)

    Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

  15. Metabolism and incorporation of orally administrated arachidonic acid in rats

    International Nuclear Information System (INIS)

    Magni, F.; Kikawa, Y.; Jedlinski, A.; Lands, W.E.M.

    1986-01-01

    50 mg 3 H 2 H-20: 4n-6 was administered by oral intubation to rats maintained on a normal diet. The distribution of radioactive arachidonate esterified in the various tissues was similar to that for EFA-deficient rats from their previous study. The amount incorporated in the tissues was 14% in normal rats and 16% in EFA-deficient rats. At 24 hrs, the relative radioactivity in PC was higher (and lower in PE) than after 20 days in the previous study. Urine had 3-4% of initial radioactivity in the first 12 hours and only 1% more by 24 hours. Urine components were analyzed as methyl ester-methoxime-t-butyldimethylsilyl ethers. Most of the arachidonate metabolites in urine reported in the literature have expected ECL values between 26 to 32, whereas they found 68% of radioactivity with ECL values below 26. This represents a substantial divergence from arachidonate metabolite patterns described for injected prostaglandins and indicates the need of examining the metabolites formed from endogenously formed eicosanoids

  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. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

    Science.gov (United States)

    Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

    2016-10-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

  18. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

    Science.gov (United States)

    Owczarzak, Vicki; Haddad, Joseph

    2006-08-01

    To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

  19. Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

    Science.gov (United States)

    Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

    2018-04-01

    Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

  20. Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

    Science.gov (United States)

    Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

    2013-11-01

    Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral

  1. Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

    DEFF Research Database (Denmark)

    Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

    2007-01-01

    After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  2. Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

    Science.gov (United States)

    Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  3. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs.

    Science.gov (United States)

    Zhao, Jie; Geng, Ting; Wang, Qi; Si, Haihong; Sun, Xiaoping; Guo, Qingming; Li, Yanjing; Huang, Wenzhe; Ding, Gang; Xiao, Wei

    2015-11-06

    Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1×50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2-200 ng/mL. The intra- and inter-day precisions were dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.

  4. Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-11-01

    Full Text Available Ginkgolide B (GB, an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM in negative ion mode, with the transitions at m/z (Q1/Q3 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet. The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.

  5. Economic impact of the new oral treatments for multiple sclerosis.

    Science.gov (United States)

    Álvarez Ayuso, L; Rodríguez Marrodán, B; Blasco Quílez, M R; García-Merino, J A; Sánchez Guerrero, A

    2018-01-11

    Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of €169,107.31 over the study period. In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration.

    Science.gov (United States)

    Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Luan, Xianguo; Wang, Haifang; Jia, Guang

    2015-12-03

    Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various consumer products, especially food and personal care products. Compared to the well-characterized adverse cardiovascular effect of inhaled ambient ultrafine particles, research on the health response to orally administrated TiO2 NPs is still limited. In our study, we performed an in vivo study in Sprague-Dawley rats to understand the cardiovascular effect of TiO2 NPs after oral intake. After daily gastrointestinal administration of TiO2 NPs at 0, 2, 10, 50 mg/kg for 30 and 90 days, heart rate (HR), blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. Mild and temporary reduction of HR and systolic blood pressure as well as an increase of diastolic blood pressure was observed after daily oral administration of TiO2 NPs for 30 days. Injury of cardiac function was observed after daily oral administration of TiO2 NPs for 90 days as reflected in decreased activities of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH) and creatine kinase (CK). Increased white blood cells count (WBC) and granulocytes (GRN) in blood as well as increased concentrations of tumor necrosis factor α (TNF α) and interleukin 6 (IL-6) in the serum indicated inflammatory response initiated by TiO2 NPs exposure. It was hypothesize that cardiac damage and inflammatory response are the possible mechanisms of the adverse cardiovascular effects induced by orally administrated TiO2 NPs. Data from our study suggested that even at low dose of TiO2 NPs can induce adverse cardiovascular effects after 30 days or 90 days of oral exposure, thus warranting concern for the dietary intake of TiO2 NPs for consumers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    Directory of Open Access Journals (Sweden)

    Tomohiro Osaki

    2015-08-01

    Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

  8. Development of Alginate Microspheres Containing Chuanxiong for Oral Administration to Adult Zebrafish

    Directory of Open Access Journals (Sweden)

    Li-Jen Lin

    2016-01-01

    Full Text Available Oral administration of Traditional Chinese Medicine (TCM by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease.

  9. Novel oral administrated paclitaxel micelles with enhanced bioavailability and antitumor efficacy for resistant breast cancer.

    Science.gov (United States)

    Zhang, Ting; Luo, Jingwen; Fu, Yao; Li, Hanmei; Ding, Rui; Gong, Tao; Zhang, Zhirong

    2017-02-01

    Paclitaxel (PTX) is a widely used antineoplastic drug in clinic. Due to poor aqueous solubility, it is administrated by intravenous infusion of cremophor EL containing formulation with serious adverse effects. The low oral bioavailability is a great challenge for oral formulation development. In addition, P-gp mediated multidrug resistance limit its clinical use in various resistant cancers. In this study, a novel super-antiresistant PTX micelle formulation for oral administration was developed. A P-gp inhibitor, bromotetrandrine (W198) was co-encapsulated in the micelle. The micelles were composed of Solutol HS 15 and d-a-tocopheryl polyethylene glycol succinate to avoid Cremophor EL induced toxicity. The micelles were round with a mean particle size of ∼13nm and an encapsulation efficiency of ∼90%. A series of in vitro evaluations were performed in non-resistant MCF-7 cells and resistant MCF-7/Adr cells. The super-antiresistant PTX micelles showed higher cell uptake efficiency, significantly increased cytotoxicity and antimitotic effect in drug resistant MCF-7/Adr cells when compared with Taxol and other PTX micelle formulations. Compared with Taxol, the super-antiresistant PTX micelles significantly improved bioavailability after oral administration in rats, and inhibited tumor growth in multidrug resistance xenografted MCF-7/Adr nude mice. In summary, the noval super-antiresistant PTX micelles showed a great potential for oral delivery of PTX against resistant breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

    Science.gov (United States)

    Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

    2011-06-01

    Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

  11. Two cases of "cannabis acute psychosis" following the administration of oral cannabis

    Directory of Open Access Journals (Sweden)

    Pin Marie

    2005-04-01

    Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

  12. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

  13. Calcium metabolism in children suffering from homozygous β-thalassaemia after oral administration of 47Ca

    International Nuclear Information System (INIS)

    Liakakos, D.; Vlachos, P.; Anoussakis, C.; Constantinides, C.; Tsakalosos, I.; Alexandra Hospital, Athens

    1976-01-01

    The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47 Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia. (orig.) [de

  14. Oral administration of piperine for the control of aflatoxin intoxication in rats.

    Science.gov (United States)

    Gagini, Thalita B; Silva, Robson E; Castro, Isabela S; Soares, Breno A; Lima, Marco E F; Brito, Marilene F; Mazur, Carlos; Direito, Glória M; Danelli, Maria das Graças M

    2010-04-01

    Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

  15. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    Science.gov (United States)

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATEMichael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas11US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  16. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  17. Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ehsan Zayerzadeh

    2016-07-01

    Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

  18. Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

    Science.gov (United States)

    Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

    2013-09-01

    Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

  19. Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

    NARCIS (Netherlands)

    Maassen, C.B.M.; Laman, J.D.; Heijne den Bak-Glashouwer, M.J.; Tielen, F.J.; Holten-Neelen, J.C.P.A. van; Hoogteijling, L.; Antonissen, C.; Leer, R.J.; Pouwels, P.H.; Boersma, W.J.A.; Shaw, D.M.

    1999-01-01

    Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in

  20. Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

    Directory of Open Access Journals (Sweden)

    Gabriela A. Albarellos

    2013-10-01

    Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

  1. Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

    Science.gov (United States)

    Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

    2011-08-01

    Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

  2. PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

    Science.gov (United States)

    Kasperek, Regina; Zimmer, Łukasz; Jawień, Wojciech; Poleszak, Ewa

    2015-01-01

    Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

  3. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  4. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

    International Nuclear Information System (INIS)

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

    1986-01-01

    Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

  5. 20 CFR 416.1448 - Deciding a case without an oral hearing before an administrative law judge.

    Science.gov (United States)

    2010-04-01

    ... § 416.1448 Deciding a case without an oral hearing before an administrative law judge. (a) Decision... the decision is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

  6. 20 CFR 404.948 - Deciding a case without an oral hearing before an administrative law judge.

    Science.gov (United States)

    2010-04-01

    ....948 Deciding a case without an oral hearing before an administrative law judge. (a) Decision wholly... is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide a case on... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

  7. Conscious sedation by oral administration of midazolam in paediatric dental treatment.

    Science.gov (United States)

    Erlandsson, A L; Bäckman, B; Stenström, A; Stecksén-Blicks, C

    2001-01-01

    Midazolam is a short-acting benzodiazepine with rapid onset, short duration of action and minimal side effects. The aim of this study was to evaluate the oral administration of midazolam as pre-operative sedation in the dental treatment of uncooperative pediatric patients. Included in the study were 160 children with a mean age of 6.7 +/- 2.6 years (1-14 years), 83 boys and 77 girls. All the patients had been referred for specialist treatment due to behavioral management problems. Treatment was performed in 250 sessions. All the children received an oral dose of 0.2 mg/kg body weight of midazolam. Acceptance of treatment was evaluated according to Rud & Kisling. Local anesthesia followed by restorative treatment and/or extractions constituted more than 90% of the performed treatments. Of the 250 sessions, 63% were performed with total acceptance and 30% with doubtful acceptance. In 7%, no treatment could be performed. No serious complications were registered during or after treatment. All the children were able to leave the clinic one hour after treatment. In conclusion, we consider oral administration of midazolam a safe form of premedication. The route of administration, the short waiting-time and half-life, in combination with a level of sedation that allows treatment to be performed, are the principal advantages of conscious sedation with orally administered midazolam.

  8. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Science.gov (United States)

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  9. Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella

    International Nuclear Information System (INIS)

    Zhao Lihua; Liu Bin; Yu Xiaofei; Zhang Lei; Han Zhongchao

    2005-01-01

    Objective: To investigate the in vivo radiation protection effect of PF4 by oral administration of attenuated salmonella as the carrier in mice. Methods: The eukaryotic vector pIRES2-EGFP-carried PF4 gene was transferred into an aroA-autotrophic mutant of salmonella typhimurium (SL3261), which was administered orally to BALBPc mice at 1x10 8 PFu once every interval three days. At 12 hours after the third oral administration the mice were subjected to a total body irradiation (TBI) of 700 cGy by a 60 Co source. The protective effect of SL3261/PF4 was determined by detection GFP ( green fluorescence protein) expression in tissues, peripheral blood count, culture of bone marrow colony-forming cells and survival time of mice. Results: Expression of GFP could be detected in the liver, spleen, intestine, kidney, peripheral blood and bone marrow. On days 7 and 14 after irradiation, Compared to controls, there were obvious differences in number of bone marrow mononuclear cells, CFU-GM (granulocyte-macrophage colony-forming unit ) and HPP-CFC (high proliferating potential-colony-forming cells) of mice treated with SL3261/PF4 (P<0.05) as well as prolongation of the survival time. Conclusion: These data demonstrate for the first time that PF4 protects mice from TBI injury and accelerates recovery of hematopoiesis by oral administration of attenuated salmonella carrying PF4 gene. (authors)

  10. Pharmacokinetics of /sup 3/H-pipethiaden after single oral and intravenous administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lapka, R.; Franc, Z.; Smolik, S.

    1985-01-01

    Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-duhydrothieno(2,3-c)-2-benzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t/sub 1/2/el-4h) were calculated by compartmental analysis of plasma levels.

  11. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  12. Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

    2016-01-01

    Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

  13. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

    NARCIS (Netherlands)

    De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

    The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

  14. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  15. Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

    Science.gov (United States)

    Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

    2010-03-01

    We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

  16. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  17. Detection of capecitabine (Xeloda®) on the skin surface after oral administration

    Science.gov (United States)

    Huang, Mao-Dong; Fuss, Harald; Lademann, Jürgen; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora

    2016-04-01

    Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, ptoxic effect as a possible pathomechanism of PPE.

  18. Effect of Oral Administration of “Gadagi” Tea on Lipid Profile in Rats ...

    African Journals Online (AJOL)

    Abstract: Effect of oral administration of “Gadagi” tea on lipid profile was assessed in 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg,. 315mg/kg for “sak”, ”sada” and “magani” respectively), standard dose (760mg/kg, 830mg/kg, ...

  19. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    Science.gov (United States)

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    International Nuclear Information System (INIS)

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-01-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

  1. Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

    Science.gov (United States)

    Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

    2009-01-01

    The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

  2. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

    2011-09-01

    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (Amazon

  3. Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

    Science.gov (United States)

    Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

    2015-12-01

    Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese.

  4. Pharmacokinetics of [3H]levamisole in pigs after oral and intramuscular administration

    International Nuclear Information System (INIS)

    Galtier, P.; Escoula, L.; Alvinerie, M.

    1983-01-01

    A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of [ 3 H]levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease

  5. Pharmacokinetics of (/sup 3/H)levamisole in pigs after oral and intramuscular administration

    Energy Technology Data Exchange (ETDEWEB)

    Galtier, P.; Escoula, L.; Alvinerie, M.

    1983-04-01

    A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of (/sup 3/H)levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease.

  6. Protective effect of oral administration of transgenic tobacco seeds against verocytotoxic Escherichia coli strain in piglets.

    Science.gov (United States)

    Rossi, Luciana; Dell'Orto, Vittorio; Vagni, Simona; Sala, Vittorio; Reggi, Serena; Baldi, Antonella

    2014-03-01

    The use of transgenic plants as delivery system for antigenic proteins is attractive for its simplicity and increases likelihood for local immune response at sites of infection. The aim of this study was to evaluate the protective effect of oral administration of tobacco seeds, expressing the FedA, the major protein of the F18 adhesive fimbriae, and B subunit of verocytotoxin, against verocytotoxin-producing E. coli (VTEC) strain in piglets. Forty-three early weaned piglets, were randomly divided into 4 experimental groups: 3 test groups and a control. Treatment groups orally received a bolus, with different dose of tobacco seeds on 0, 1, 2, 14 days post primary administration. After challenge, with 1*10(10) CFU of O138 Escherichia coli strain, piglets showed clinical scores significantly higher in the control group compared to orally immunized groups (P administration of recombinant tobacco seeds expressing antigenic proteins against VTEC strains can induce a protective effect against challenger strain in piglets.

  7. Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

    Science.gov (United States)

    Deleu, Dirk; Mesraoua, Boulenouar; Canibaño, Beatriz; Melikyan, Gayane; Al Hail, Hassan; El-Sheikh, Lubna; Ali, Musab; Al Hussein, Hassan; Ibrahim, Faiza; Hanssens, Yolande

    2018-06-18

    The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

  8. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Science.gov (United States)

    Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

    2015-01-01

    Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  9. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  10. Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2012-08-01

    To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

  11. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  12. Studies on the absorption of iron after oral administration in piglets

    International Nuclear Information System (INIS)

    Thoren-Tolling, K.

    1975-01-01

    72 newborn piglets from 9 litters were used to determinate the retention and distribution in the body of labelled iron given either orally as ferrous fumarate (100 mg Fe 2+ ) or iron dextran (200 mg Fe 3+ ), or by injection as iron dextran (100 mg Fe 3+ ). About 25-30 % of the radioiron from a single oral dose of labelled ferrous fumarate (100 mg Fe 2+ ), and about 55-60 % from a single oral dose of labelled iron dextran (200 mg Fe 3+ ) were absorbed by the body. As iron is excreted throughout the experiment, only about 20% and 40-50% respectively of the radio-iron from these iron compounds were recovered 3 weeks after treatment. The total amounts of labelled iron retained in the body after oral administration of the same doses of these iron compounds, alone or in combination, were compared. A slight retardation of the absorption of ferrous iron was observed when iron dextran was administered simultaneeously. The absorption of iron dextran was not influenced by the simultaneous administration of ferrous fumarate. The importance of the liver as the main iron storage site was shown, and the rapid utilization of iron from storage sites, about 2-3 weeks after treatment was demonstrated. The concentration of labelled iron in urine and some lymphglands was measured. Only minute quantities of radio-iron were excreted in the urine throughout the entire experiment. The lymph nodes seem to act as iron stones after administration of iron dextran. The importance of the lymphatic tissue in absorption and storage of labelled iron is discussed. (author)

  13. Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

    Directory of Open Access Journals (Sweden)

    Federica Di Cesare

    2017-05-01

    Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

  14. Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

    Science.gov (United States)

    Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

    2015-01-01

    DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

  15. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S.Talluri

    2009-10-01

    Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  16. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Science.gov (United States)

    Talluri, Ravi S.; Gaudana, Ripal; Hariharan, Sudharshan; Mitra, Ashim K.

    2009-01-01

    Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

  17. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S. Talluri

    2009-01-01

    Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  18. Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy.

    Science.gov (United States)

    Fernández, Leónides; Cárdenas, Nivia; Arroyo, Rebeca; Manzano, Susana; Jiménez, Esther; Martín, Virginia; Rodríguez, Juan Miguel

    2016-03-01

    Previous studies have shown that oral administration of lactobacilli can be an efficient approach to treat lactational infectious mastitis. In this trial, we have evaluated the potential of Lactobacillus salivarius PS2 to prevent this condition when orally administered during late pregnancy to women who had experienced infectious mastitis after previous pregnancies. In this study, 108 pregnant women were randomly assigned to one of 2 groups. Those in the probiotic group (n = 55) ingested daily 9 log10 colony-forming units of L. salivarius PS2 from approximately week 30 of pregnancy until delivery, whereas those in the placebo group (n = 53) received a placebo. The occurrence of mastitis was evaluated during the first 3 months after delivery. Globally, 44 of 108 women (41%) developed mastitis; however, the percentage of women with mastitis in the probiotic group (25% [n = 14]) was significantly lower than in the control group (57% [n = 30]). When mastitis occurred, the milk bacterial counts in the probiotic group were significantly lower than those obtained in the placebo group. Oral administration of L. salivarius PS2 during late pregnancy appears to be an efficient method to prevent infectious mastitis in a susceptible population. NCT01505361. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

    Science.gov (United States)

    Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

    2015-10-01

    [Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

  20. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

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    Iwao Sasaki

    2010-09-01

    Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

  1. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

    Science.gov (United States)

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future

  2. Metabolic fate of poly-(lactic-co-glycolic acid-based curcumin nanoparticles following oral administration

    Directory of Open Access Journals (Sweden)

    Harigae T

    2016-06-01

    Full Text Available Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: Curcumin (CUR, the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid-based CUR nanoparticles (CUR-NP have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG, the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.Methods: Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.Results: Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with

  3. Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water.

    Science.gov (United States)

    Prohaczik, Angella; Menge, Monika; Huyghe, Bruno; Flochlay-Sigognault, Annie; Traon, Gaëlle Le

    2017-08-08

    Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose. One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology

  4. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration

    DEFF Research Database (Denmark)

    Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik

    2014-01-01

    The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine...

  5. Failure mode and effects analysis applied to the administration of liquid medication by oral syringes

    Directory of Open Access Journals (Sweden)

    Eva María Guerra-Alia

    2017-11-01

    Full Text Available To carry out a Failure Mode and Effects Analysis (FMEA to the use of oral syringes. Methods: A multidisciplinary team was assembled within the Safety Committee. The stages of oral administration process of liquid medication were analysed, identifying the most critical and establishing the potential modes of failure that can cause errors. The impact associated with each mode of failure was calculated using the Risk Priority Number (RPN. Preventive actions were proposed. Results: Five failure modes were identified, all classified as high risk (RPN> 100. Seven of the eight preventive actions were implemented. Conclusions: The FMEA methodology was a useful tool. It has allowed to know the risks, analyse the causes that cause them, their effects on patient safety and the measures to reduce them

  6. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    Science.gov (United States)

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  7. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral...

  8. Evaluation of student nurses' perception of preparedness for oral medication administration in clinical practice: a collaborative study.

    Science.gov (United States)

    Aggar, Christina; Dawson, Sonja

    2014-06-01

    Attainment of oral medication administration skills and competency for student nurses is challenging and medication errors are common. The ability of nurses to master a clinical skill is dependent upon educational instruction and practice. The aim of this study was to evaluate nursing students' perception of preparedness for oral medication administration in two practice environments and determine possible relationship between student demographics and their perceived preparedness for oral medication administration. This was a cross sectional, exploratory study. Eighty-eight second year students from a baccalaureate nursing course from two metropolitan Australian tertiary institutions participated. Student nurses' perception of preparedness for oral medication administration was measured via a self-administered, adapted, and validated questionnaire. The overall mean Total Preparedness Score was 86.2 (range 71-102). There was no significant difference for perceived total preparedness to administer oral medications between the two facilities. Whilst there was no significant relationship established between student demographics and their perceived preparedness to administer oral medications, four single questions related to clinical practice were shown to be significant. Low fidelity simulated teaching environments that incorporate time management and post medication situations, may improve student nurses' perceived preparedness for oral medication administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    Johansson, E.; Gillespie, H.K.; Halldin, M.M.

    1990-01-01

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

  10. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    Science.gov (United States)

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

    Science.gov (United States)

    Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

    2011-06-18

    Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

    OpenAIRE

    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 ...

  13. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    Science.gov (United States)

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Studies on portal systemic circulation by oral administration of 201Tl enclosed enteric coated capsule

    International Nuclear Information System (INIS)

    Tonami, Norihisa; Nakajima, Kenichi; Watanabe, Naoto

    1986-01-01

    Thallium-201 enclosed enteric coated capsule was prepared and administered orally to evaluate portal systemic circulation in 11 control subjects and 31 patients with various liver diseases by investigating scintigraphic appearance and the heart-to-liver uptake ratio (H/L ratio). In 10 patients with liver cirrhosis and one with chronic hepatitis, the results of H/L ratio were compared to those obtained by 201 Tl per-rectal administration. 1. It was fundamentally confirmed that 201 Tl enclosed enteric coated capsule was not broken down in the artificial gastric juice, but nearly completely melted 15 minutes after soaking in the artificial intestinal juice. 2. Clinical study was successfully completed in 36 out of 42 cases (86 %). Unsuccessful cases were found in 2 with capsule collapse in the stomach and 4 with its poor moving to the duodenum. 3. In control subjects the liver was clearly visualized and the mean value of H/L ratio was 0.32 which is lower than that of 201 Tl per-rectal administration previously reported. H/L ratio in patients with chronic and acute hepatitis was nearly equal to that in control subjects. H/L ratio in patients with liver cirrhosis was slightly higher than that in control subjects, but there was no significant difference between them. In cases with esophageal varices, H/L ratio was not so high compared to that in control subjects. Out of 7 patients showing high H/L ratio more than 0.8 in 201 Tl per-rectal administration, only one showed similar high ratio (1.07) in oral administration of 201 Tl enclosed enteric coated capsule. In this case the shunting from superior mesenteric vein to inferior vena cava connection was confirmed. From these results, it was considered that the shunting volume of superior mesenteric vein through esophageal varices is small. 4. A possibility of a new administration of radioisotope with enteric coated capsule was emphasized. (author)

  15. Oral administration of yessotoxin stabilizes E-cadherin in mouse colon

    International Nuclear Information System (INIS)

    Callegari, Federica; Sosa, Silvio; Ferrari, Sara; Soranzo, Maria Rosa; Pierotti, Silvia; Yasumoto, Takeshi; Tubaro, Aurelia; Rossini, Gian Paolo

    2006-01-01

    YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1 mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA 9 ), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA 9 , as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo

  16. Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

    Science.gov (United States)

    Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

    2017-11-01

    Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration

    International Nuclear Information System (INIS)

    Dutcher, J.S.; Sun, J.D.; Bechtold, W.E.; Unkefer, C.J.

    1985-01-01

    The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [ 14 C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14 C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 0 C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures

  18. Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

    Science.gov (United States)

    Gharibi, S; Kimble, B; Vogelnest, L; Barnes, J; Stadler, C K; Govendir, M

    2017-12-01

    The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ss ) were 0.15 (0.13-0.18) L hr -1  kg -1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t 1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C max ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas. © 2017 John Wiley & Sons Ltd.

  19. Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

    DEFF Research Database (Denmark)

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single...... bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit....

  20. Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

    DEFF Research Database (Denmark)

    Liu, Wenli; Wang, Xiaona; Chen, Ruilian

    2016-01-01

    The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from...... and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application...

  1. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

    Directory of Open Access Journals (Sweden)

    Giuseppe Benagiano

    2009-04-01

    Full Text Available Giuseppe Benagiano, Sabina Carrara, Valentina FilippiDepartment of Gynaecology and Obstetrics, Sapienza University, Rome, ItalyAbstract: The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic and peripheral (cervical mucus and endometrium levels. Levonorgestrel (LNG, alone or in combination with ethinyl estradiol (EE, is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years

  2. Orthodontic treatment for oral rehabilitation after multiple maxillofacial bone fractures.

    Science.gov (United States)

    Nakamura, Yoshiki; Ogino, Tomoko Kuroiwa; Hirashita, Ayao

    2008-09-01

    We present the orthodontic treatment of a patient with occlusal dysfunction after plastic surgery for multiple maxillofacial bone fractures caused by a traffic accident. The patient had mandibular deviation to the right because of inappropriate repositioning and fixation of the fractured bone and complete avulsion of both mandibular central incisors. The bilateral mandibular incisors, canines, and premolars were also suspected of partial avulsion or alveolar bone fracture. Several tests, including percussion and dental computed tomography, were performed on these teeth to rule out ankylosis and confirm tooth movement. Camouflage orthodontic treatment was carried out with expansion of the maxillary arch, alignment of both arches, and space closure between the mandibular lateral incisors to improve the occlusion. Good occlusion and interdigitation were obtained. Orthodontic treatment is useful for the rehabilitation of occlusal dysfunction caused by multiple maxillofacial bone fractures.

  3. Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

    Science.gov (United States)

    Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

    2005-05-01

    To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

  4. Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

    Science.gov (United States)

    Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

    2014-01-01

    To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  5. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    Science.gov (United States)

    Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

    2011-01-01

    Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

  6. Effect of oral administration of carprofen on intraocular pressure in normal dogs.

    Science.gov (United States)

    Meekins, J M; Overton, T L; Rankin, A J; Roush, J K

    2016-08-01

    The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11-day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1-11) and treatment (days 12-18) phases and for 48 h (days 19-20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12-18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety-related effects on IOP measurements. © 2016 John Wiley & Sons Ltd.

  7. Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

    Science.gov (United States)

    Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

    2016-04-29

    Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

    Science.gov (United States)

    Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

    2017-11-01

    Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

  9. Design and development of a lead jar for oral administration of radioiodine In hyperthyroid patients

    International Nuclear Information System (INIS)

    Rahman, M.S.; Paul, A.K.; Rahman, H.A.; Begum, F.

    2005-01-01

    Full text: Nuclear Medicine practices involve use of radioisotopes for diagnosis and treatment of diseases. Radioiodine is one of such radioisotopes, being used in the diagnosis and treatment of diseases since 1942. Handling of radioiodine involves radiation hazards both for the patients as well as for the technologists. Though radioiodine is supplied in a lead container, for treatment purpose, it is administered after dispensing into a glass jar that does not adequately protect radiation hazards. For this reason, we designed and developed a lead jar and radioiodine is dispensed into that lead jar to minimize radiation hazards. For oral administration of radioiodine to hyperthyroid patients, a lead jar was designed and developed with lead in Centre for Nuclear Medicine and Ultrasound, Khulna in December 2004 by own expertise and technologies in such a way that a glass jar could be introduced into that lead jar. The thickness of lead was 4.04 mm and the thickness of glass jar was 0.7 mm and thus the whole thickness of lead jar became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar and administered orally to the patients. Radiation levels in 10 such cases were measured by Mini-Rad Series-1000 survey meter at 0.5 meter, 1 meter and 3 meters distances both lead jar and glass jar. The mean radiation level of lead jar and glass jar during oral administration of 8 mCi of Na 131 I solution in 10 cases at 0.5 meter, 1 meter and 3 meters distances were 62.4 ± 1.96 microSv/h, 17.7 ±1.95 microSv/h, 3.39 ± .12 microSv/h and 20.3± 2.16 microSv/h, 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. In conclusion, the locally designed and developed lead jar is safe, easy to handle and reduces radiation burden significantly in oral administration of radioiodine to

  10. Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo

    Directory of Open Access Journals (Sweden)

    Victoria A. Meliopoulos

    2016-11-01

    Full Text Available The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1 capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2 capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3 from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

  11. Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

    Science.gov (United States)

    Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

    2018-02-01

    The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

  12. Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

    Science.gov (United States)

    Mackay, Robert J; Tanhauser, Susan T; Gillis, Karen D; Mayhew, Ian G; Kennedy, Tom J

    2008-03-01

    To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. 20 healthy horses that were seronegative for S neurona-specific IgG. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

  13. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    Science.gov (United States)

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

    Science.gov (United States)

    Adeneye, A A; Benebo, A S

    2007-01-01

    Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

  15. Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

    Science.gov (United States)

    Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

    2010-03-01

    Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

  16. Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration.

    Science.gov (United States)

    Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Chen, Tian; Li, Yang; Zhang, Wenxiao; Gao, Xin; Li, Ping; Wang, Haifang; Jia, Guang

    2015-10-01

    Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

    Directory of Open Access Journals (Sweden)

    Xinhuan Wan

    2014-12-01

    Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

  18. Disposition Kinetics of Amoxicillin in Healthy, Hepatopathic and Nephropathic Conditions in Chicken after Single Oral Administration

    Directory of Open Access Journals (Sweden)

    Moloy Kumar Bhar

    2010-12-01

    Full Text Available Fifteen broiler chickens (COBB 400 of 42 days of age weighing 1.8 to 2.0 kg were equally divided into 3 groups, each consisting of 5 birds. Hepatopathy was induced by oral administration of paracetamol while nephropathy was induced by intravenous administration of uranyl nitrate. Kinetic study was investigated in healthy, hepatopathic and nephropathic birds following single oral administration of amoxicillin at 40 mg kg-1. Blood samples were collected at different time schedule. Plasma concentrations of amoxicillin in healthy, hepatopathic and nephropathic birds were 41.90 ± 5.59, 9.93 ± 0.76 and 38.75 ± 6.08 µg ml-1, respectively at 1 hr; 15.34 ± 1.99, 18.57 ± 1.66 and 67.40 ± 2.62 µg ml-1, respectively at 4 hr and 2.03 ± 0.28, 15.54 ± 0.82 and 30.63 ± 1.58 µg ml-1, respectively at 24 hr. Maximum plasma concentration was detected at 1 hr in healthy birds (41.90 ± 5.59 µg ml-1 , at 8 hr in hepatopathic birds (23.51 ± 1.64 µg ml-1 and at 4 hr in nephropathic birds (67.40 ± 2.62 µg ml-1. The drug could not be detected in plasma beyond 24 hr in healthy, 72 hr in both hepatopathic and nephropathic birds. The concentration of amoxicillin was significantly (P < 0.01 higher in most of the samples of hepatopathic and nephropathic birds compared to healthy birds. Significant higher values (P < 0.01 of t1/2 K, AUC, and MRT and lower values of K and ClB in the hepatopathic and nephropathic birds in comparison to healthy birds were observed.

  19. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

    Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

  20. Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

    Science.gov (United States)

    Corado, Carley R; McKemie, Daniel S; Knych, Heather K

    2017-06-01

    Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Labeling of red blood cells with Tc-99m after oral administration of SnCl2. Concise communication

    International Nuclear Information System (INIS)

    Patel, M.C.; Parab, P.B.; Samuel, A.M.; Ganatra, R.D.

    1979-01-01

    In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl 2 , both in rats and human volunteers. Absorption of oral SnCl 2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloide. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of /sup 99m/TcO 4 - in rats that were fed 5 mg of stannous chloride (3.13 mg Sn 2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl 2 . We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m - such as the amount of orally administered SnCl 2 , the time of injection of radionuclide after oral SnCl 2 , and the optimum time for the imaging

  2. A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jutta Ries

    2009-01-01

    Full Text Available Objective: Melanoma associated antigens-A (MAGE-A expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC.

  3. Studies on portal systemic circulation by oral administration of /sup 201/Tl enclosed enteric coated capsule

    Energy Technology Data Exchange (ETDEWEB)

    Tonami, Norihisa; Nakajima, Kenichi; Watanabe, Naoto and others

    1986-03-01

    Thallium-201 enclosed enteric coated capsule was prepared and administered orally to evaluate portal systemic circulation in 11 control subjects and 31 patients with various liver diseases by investigating scintigraphic appearance and the heart-to-liver uptake ratio (H/L ratio). In 10 patients with liver cirrhosis and one with chronic hepatitis, the results of H/L ratio were compared to those obtained by /sup 201/Tl per-rectal administration. 1. It was fundamentally confirmed that /sup 201/Tl enclosed enteric coated capsule was not broken down in the artificial gastric juice, but nearly completely melted 15 minutes after soaking in the artificial intestinal juice. 2. Clinical study was successfully completed in 36 out of 42 cases (86 %). Unsuccessful cases were found in 2 with capsule collapse in the stomach and 4 with its poor moving to the duodenum. 3. In control subjects the liver was clearly visualized and the mean value of H/L ratio was 0.32 which is lower than that of /sup 201/Tl per-rectal administration previously reported. H/L ratio in patients with chronic and acute hepatitis was nearly equal to that in control subjects. H/L ratio in patients with liver cirrhosis was slightly higher than that in control subjects, but there was no significant difference between them. In cases with esophageal varices, H/L ratio was not so high compared to that in control subjects. Out of 7 patients showing high H/L ratio more than 0.8 in /sup 201/Tl per-rectal administration, only one showed similar high ratio (1.07) in oral administration of /sup 201/Tl enclosed enteric coated capsule. In this case the shunting from superior mesenteric vein to inferior vena cava connection was confirmed. From these results, it was considered that the shunting volume of superior mesenteric vein through esophageal varices is small. 4. A possibility of a new administration of radioisotope with enteric coated capsule was emphasized.

  4. TRANSDERMAL ADMINISTRATION OF THE DOPAMINE AGONIST N-0437 AND 7 ESTER PRODRUGS - COMPARISON WITH ORAL-ADMINISTRATION IN THE 6-OHDA TURNING MODEL

    NARCIS (Netherlands)

    DENDAAS, [No Value; TEPPER, PG; ROLLEMA, H; HORN, AS

    1990-01-01

    The potent and selective D2-agonist N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] undergoes considerable first-pass metabolism after oral administration due to glucuronidation of the phenolic group. In an attempt to improve its bioavailability, seven ester prodrugs of N-0437 were

  5. Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

    International Nuclear Information System (INIS)

    Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

    2006-01-01

    3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

  6. Oral administration of kefiran exerts a bifidogenic effect on BALB/c mice intestinal microbiota.

    Science.gov (United States)

    Hamet, M F; Medrano, M; Pérez, P F; Abraham, A G

    2016-01-01

    The activity of kefiran, the exopolysaccharide present in kefir grains, was evaluated on intestinal bacterial populations in BALB/c mice. Animals were orally administered with kefiran and Eubacteria, lactobacilli and bifidobacteria populations were monitored in faeces of mice at days 0, 2, 7, 14 and 21. Profiles obtained by Denaturing Gradient Gel Electrophoresis (DGGE) with primers for Eubacteria were compared by principal component analysis and clearly defined clusters, correlating with the time of kefiran consumption, were obtained. Furthermore, profile analysis of PCR products amplified with specific oligonucleotides for bifidobacteria showed an increment in the number of DGGE bands in the groups administered with kefiran. Fluorescent In Situ Hybridisation (FISH) with specific probes for bifidobacteria showed an increment of this population in faeces, in accordance to DGGE results. The bifidobacteria population was also studied on distal colon content after 0, 2 and 7 days of kefiran administration. Analysis of PCR products by DGGE with Eubacteria primers showed an increment in the number and intensity of bands with high GC content of mice administered with kefiran. Sequencing of DGGE bands confirmed that bifidobacteria were one of the bacterial populations modified by kefiran administration. DGGE profiles of PCR amplicons obtained by using Bifidobacterium or Lactobacillus specific primers confirmed that kefiran administration enhances bifidobacteria, however no changes were observed in Lactobacillus populations. The results of the analysis of bifidobacteria populations assessed on different sampling sites in a murine model support the use of this exopolysaccharide as a bifidogenic functional ingredient.

  7. Optical imaging of absorption and distribution of RITC-SiO2 nanoparticles after oral administration

    Directory of Open Access Journals (Sweden)

    Lee CM

    2014-12-01

    Full Text Available Chang-Moon Lee,1 Tai Kyoung Lee,2–5 Dae-Ik Kim,1,6 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Hwan-Jeong Jeong,2–5 Myung-Hee Sohn,2–5 Seok Tae Lim2–5 1Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 2Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 3Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 4Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 6School of Electrical, Electronic Communication, and Computer Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seounbuk-Gu, Seoul, Republic of Korea Purpose: In this study, we investigated the absorption and distribution of rhodamine B isothiocyanate (RITC-incorporated silica oxide nanoparticles(SiNPs (RITC-SiNPs after oral exposure, by conducting optical imaging, with a focus on tracking the movement of RITC-SiNPs of different particle size and surface charge. Methods: RITC-SiNPs (20 or 100 nm; positively or negatively charged were used to avoid the dissociation of a fluorescent dye from nanoparticles via spontaneous or enzyme-catalyzed reactions in vivo. The changes in the nanoparticle sizes and shapes were investigated in an HCl solution for 6 hours. RITC-SiNPs were orally administered to healthy nude mice at a dose of 100 mg/kg. Optical imaging studies were performed at 2, 4, and 6 hours after oral administration. The mice were sacrificed at 2, 4, 6, and 10 hours post-administration, and ex vivo imaging studies were performed

  8. Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis.

    Science.gov (United States)

    Govendir, M; Black, L A; Jobbins, S E; Kimble, B; Malik, R; Krockenberger, M B

    2016-08-01

    Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 μg/mL and the AUC0-8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 μg/mL; mean AUC0-8 h : 18.1 μg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  9. Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs.

    Directory of Open Access Journals (Sweden)

    Daniela Gioeni

    2017-05-01

    Full Text Available Oral transmucosal (OTM delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.. OTM is particularly useful in aggressive animals (Santos et al. 2010. The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6: two groups received OTM administration of dexmedetomidine (10 µg/kg-1 together with butorphanol (0.2 mg/kg-1, BTF-OTM group or methadone (0.2mg/kg-1, MTD-OTM group; two groups received intramuscular (IM administration of dexmedetomidine (5 µg/kg-1 together with butorphanol (0.2 m/kg-1, BTF-IM group or methadone (0.2 mg/kg-1, MTD-IM. Heart rate (HR, respiratory rate (RR, sedation score (Gruney et al. 2009 and side effects were recorded 10 (T10, 20 (T20 and 30 (T30 minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm compared to BTF-OTM (46.16 ± 17.98; Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.

  10. The normalized administration of hybrid operating room: its practical application in managing multiple injuries

    International Nuclear Information System (INIS)

    Li Xue; Zhang Weiguo; Zhang Lianyang; Chen Tingjing; Chen Jinhua

    2011-01-01

    Objective: Through carrying out the normalized administration of hybrid operating room the application of the operating room is expanded to the performing of multiple injuries, and, in this way, the operative management become standardized and programmed, the cooperation and efficiency of hybrid operations for multiple injuries are improved and the surgeries can be ensured. Methods: According to the characteristics of hybrid interventional operation for multiple injuries, the basic construction of the hybrid operating room improved, the hybrid operation team was organized, and the administrative system as well as the working program were established. The green channel for rescuing patients with multiple injuries was set up. The cooperative behavior during interventional treatment for multiple injuries was specified. Results: The coordination and working efficiency of physicians, nurses, technicians and anesthetists were well improved. The qualified rate of lamina flow administration reached 100%. The success rate of the rescue of multiple injuries was increased. Conclusion: As one-stop complex interventional operation for multiple injuries is a new technique, there is no integrated administration system. Therefore, the establishment of standardized management of one-stop complex interventional operation is of great significance in guiding clinical practice. (authors)

  11. Oral administration of kefiran induces changes in the balance of immune cells in a murine model.

    Science.gov (United States)

    Medrano, Micaela; Racedo, Silvia M; Rolny, Ivanna S; Abraham, Analía G; Pérez, Pablo F

    2011-05-25

    The aim of the present study was to evaluate the effect of the oral administration of kefiran on the balance of immune cells in a murine model. Six week old BALB/c mice were treated with kefiran (300 mg/L) for 0, 2 and 7 days. Kefiran treatment increased the number of IgA+ cells in lamina propria after 2 and 7 days. Percentage of B220+/MHCII(high) cells in mesenteric lymph nodes (2 days) and Peyer's patches (7 days) was higher compared to untreated control mice. An increase of macrophages (F4/80+ cells) was observed in lamina propria and peritoneal cavity (2 and 7 days). In contrast, at day 7, macrophage population decreased in Peyer's patches. These results show the ability of kefiran to modify the balance of immune cells in intestinal mucosa. This property could be highly relevant for the comprehension of the probiotic effect attributed to kefir.

  12. [Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

    Science.gov (United States)

    Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

    2013-01-01

    To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

  13. Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

    Science.gov (United States)

    Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

    2017-09-01

    Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

  14. Effect of oral administration of terephthalic acid on testicular functions of rats

    International Nuclear Information System (INIS)

    Cui Lunbiao; Dai Guidong; Xu Lichun; Wang Shouling; Song Ling; Zhao Renzhen; Xiao Hang; Zhou Jianwei; Wang Xinru

    2004-01-01

    To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats

  15. Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

    Science.gov (United States)

    Qiu, Jinrong; Zhao, Tao; Liu, Qingyun; He, Jinhua; He, Dechun; Wu, Genyi; Li, Yongtao; Jiang, Chengai; Xu, Zhencheng

    2016-04-01

    Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.

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

    OpenAIRE

    Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

    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...

  17. Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

    Science.gov (United States)

    Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  18. Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Silvia I. Cazorla

    2018-04-01

    Full Text Available The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431 and L. paracasei CNCM I-1518 (Lp 1518 to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus. Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old to old age (180 days old. Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

  19. 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

  20. Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

    2013-07-01

    To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

  1. 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.

  2. Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration in the adult rat

    International Nuclear Information System (INIS)

    Smith, Jordan Ned; Campbell, James A.; Busby-Hjerpe, Andrea L.; Lee, Sookwang; Poet, Torka S.; Barr, Dana B.; Timchalk, Charles

    2009-01-01

    Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of toxicity and mechanistic studies have been conducted in animals, where CPF has been administered via a variety of different exposure routes and dosing vehicles. This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak TCPy/L-TCPy concentrations in blood (20.2 μmol/l), TCPy/L-TCPy blood AUC (94.9 μmol/l h), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline/Tween 20 compared to all other dosing scenarios (>1.5 h). These results indicate that orally administered CPF is more extensively metabolized than systemic exposures of CPF (SC and IV), and vehicle of administration also has an effect on absorption rates. Thus, equivalent doses via different routes and/or vehicles of administration could potentially lead to different body burdens of CPF, different rates of bioactivation to CPF-oxon, and different toxic responses. Simulations using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF are consistent with these possibilities

  3. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    Science.gov (United States)

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  4. Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

    Science.gov (United States)

    Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

    2006-07-01

    Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

  5. Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

    Science.gov (United States)

    Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

    2013-06-01

    We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

  6. THE EFFECTS OF ORAL ADMINISTRATION OF PROPYLENE GLYCOL AND CALCIUM PROPIONATE IN DAIRY COWS

    Directory of Open Access Journals (Sweden)

    C. GAVAN

    2009-10-01

    Full Text Available This study was designed to determine the effects of the oral administration of propylene glycol and calcium propionate on performance of dairy cows. Treatments were 10 l water (control, 10 l water+300 ml propylene glycol (GP and 10 l water+500 g calcium propionate (CP. Animals were mainly of Holstein breeds and were fed and managed in a commercial setting. The cows were divided randomly into an experimental group, n=24 (n=12 with PG and n=12 with CP and a control group, n=11. Cows received the assigned treatment within 10 hours of calving and 24 hours after calving. Health events were recorded during calving and for the first 21 days in milk (DIM. Health examinations were performed on cows that appeared not well. The cows were milked three times daily and milk production was recorded electronically. Milk solid content and somatic cell score were determinate from three consecutive milking weekly till 20 DIM and than monthly till 110 DIM. Retained placenta, hypocalcaemia, displaced abomasums, ketosis and metritis were low in treatment groups (with PG and CP. The cows receiving PG had 2.8 Kg/day grater milk production than control group. The cows receiving CP had 1.7 kg/day grater milk production than control group. Prophylactic administration of PG and CP drenches to Holstein cows may be justified by potentially higher milk yields and reduced health complications.

  7. Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Orsi, R B; Oliveira, C A F; Dilkin, P; Xavier, J G; Direito, G M; Corrêa, B

    2007-12-15

    The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were studied in male New Zealand rabbits by clinical, pathological, biochemical and sphingolipid analyses. Twenty-four animals were randomly divided into the following four experimental groups: (A) 0 mg FB(1)+0 microg AFB(1)/(kg body weight(bw)day) (control); (B) 0 mg FB(1)+30 microg AFB(1)/(kg bw day); (C) 1.5 mg FB(1)/(kg bw day)+30 microg AFB(1)/(kg bw day); (D) 1.5 mg FB(1)/(kg bw day)+0 microg AFB(1). Animals from group B and principally from group C presented clinical signs of intoxication. Rabbits from group C presented a lower body weight gain than controls. Differences were observed between intoxicated rabbits and controls with respect to absolute and relative liver and kidney weight, hepatic function, serum urea and creatinine levels and Sa/So ratio. The most frequent hepatic and renal injuries were vacuolar degeneration of the liver and kidney as shown by the histopathological and serum biochemical results. Combined administration of AFB(1) and FB(1) resulted in synergistic toxic effects both in the liver and in the kidney, but hepatic injuries were more marked.

  8. Degradation rate of praziquantel and fenbendazole in rainbow trout following oral administration.

    Science.gov (United States)

    Soukupova-Markova, Zdenka; Doubkova, Veronika; Marsalek, Petr; Svobodova, Zdenka; Papezikova, Ivana; Lang, Stepan; Navratil, Stanislav; Palikova, Miroslava

    2015-01-01

    The aim of this study was to evaluate and compare the rate of degradation and elimination of praziquantel and fenbendazole antiparasitics following oral administration to salmonids. In addition, we determine whether the length of the legal withdrawal period is sufficient for complete elimination of antiparasitic residue from the body. The use of these drugs in fish is currently considered off-label and data on degradation are not available for rainbow trout. The model species for this experiment was the rainbow trout (Oncorhynchus mykiss) and praziquantel and fenbendazole were chosen for experimental therapy. Both drugs were administered into the gastrointestinal tract using a stomach tube. Concentrations of fenbendazole and praziquantel were established through high performance liquid chromatography-tandem mass spectrometry. Our results show that concentrations of praziquantel and fenbendazole reach their maximum in the body within 24 hours of administration, with concentrations dropping sharply over the following 24 hours. With one exception, when trace amounts of both substances were found in blood plasma, the drugs were completely degraded and eliminated from the body by the end of the experiment (corresponding to 497.6 degree days). Praziquantel and fenbendazole both show a high rate of degradation and elimination from fish. As both substances were eliminated from the body within the required withdrawal period (i.e. within 500 degree days) they can be safely used based on current knowledge of their therapeutic effect for treating helminth infections.

  9. Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Seminoff, Kelsey; McKemie, Dan S

    2018-03-25

    Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the current study were to describe drug concentrations and the pharmacokinetics of grapiprant in exercised Thoroughbred horses and to develop an analytical method that could be used to regulate its use in performance horses. To that end, grapiprant, at a dose of 2 mg/kg was administered orally to 12 exercised Thoroughbred horses. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Grapiprant remained above the LOQ of the assay (0.005 ng/mL) in serum for 72 hours post administration and urine concentrations were above the LOQ until 96 hours. The C max , T max and elimination half-life were 31.9 ± 13.9 ng/mL, 1.5 ± 0.5 hours and 5.86 ± 2.46 hours, respectively. The drug was well tolerated in all horses at a dose of 2 mg/kg. Results support further study of this compound in horses. Furthermore, development of a highly sensitive analytical method demonstrate that this compound can be adequately regulated in performance horses. Copyright © 2018 John Wiley & Sons, Ltd.

  10. Use of a powered shaver to remove multiple oral cavity papillomas.

    Science.gov (United States)

    Miller, Robert Sean; Tami, Thomas A

    2005-05-01

    We report a previously undescribed method of removing multiple oral papillomas, which we performed on 5 men with human immunodeficiency virus (HIV) infection. Patients were brought to the operating room and placed under general anesthesia. In addition, 1% lidocaine with 1:100,000 epinephrine was injected under and around the lesions. We then removed the lesions with a Tricut laryngeal blade attached to a handheld powered shaver Postoperatively, patients were sent home on clindamycin, a pain medication, and Peridex. At the 1-week follow-up, patients reported only minimal pain, and their wounds were well healed. We observed no adverse events associated with the shaving procedure. Our method expedites the process of removing multiple oral cavity papillomas while reducing the morbidity generally associated with other procedures.

  11. Preparation, characterization and bioavailability by oral administration of O/W curcumin nanoemulsions stabilized with lysophosphatidylcholine.

    Science.gov (United States)

    Chávez-Zamudio, Rubi; Ochoa-Flores, Angélica A; Soto-Rodríguez, Ida; Garcia-Varela, Rebeca; García, Hugo Sergio

    2017-09-20

    Curcumin is the main and most abundant bioactive component in Curcuma longa L. with documented properties in the prevention and treatment of chronic degenerative and infectious diseases. However, curcumin has low solubility in aqueous media, hence low bioavailability when administered orally. The use of nanoemulsions as carriers can provide a partial solution to bioavailability restrictions. In our study, O/W nanoemulsions of curcumin were prepared using lysophosphatidylcholine, a phospholipid with proven emulsification capacity; nevertheless, such qualities have not been previously reported in the preparation of nanoemulsions. Lysophosphatidylcholine was obtained by enzymatic removal of one fatty acid residue from phosphatidylcholine. The objective of our work was to formulate stable curcumin nanoemulsions and evaluate their bioavailability in BALB/c mice plasma after oral administration. Formulated nanoemulsions had a droplet size mean of 154.32 ± 3.10 nm, a polydispersity index of 0.34 ± 0.07 and zeta potential of -10.43 ± 1.10 mV; stability was monitored for 12 weeks. Lastly, in vivo pharmacokinetic parameters, using BALB/c mice, were obtained; namely, C max of 610 ± 65.0 μg mL -1 and T max of 2 h. Pharmacokinetic data revealed a higher bioavailability of emulsified as opposed to free curcumin. Research regarding other potential emulsifiers that may provide better health benefits and carry nano-encapsulated bioactive compounds more effectively, is necessary. This study provides important data on the preparation and design of nanoencapsulated Curcumin using lysophosphatidylcholine as an emulsifier.

  12. Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

    Directory of Open Access Journals (Sweden)

    Menéndez R.

    2000-01-01

    Full Text Available The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS. When D002 (5-100 mg/kg body weight was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46% occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40% and brain (28-44% microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

  13. Preparation and characterization of amorphous amphotericin B nanoparticles for oral administration through liquid antisolvent precipitation.

    Science.gov (United States)

    Zu, Yuangang; Sun, Wei; Zhao, Xiuhua; Wang, Weiguo; Li, Yong; Ge, Yunlong; Liu, Ying; Wang, Kunlun

    2014-03-12

    We prepared amphotericin B (AmB) nanoparticles through liquid antisolvent precipitation (LAP) and by freeze-drying to improve the solubility of AmB for oral administration. The LAP was optimized through a single-factor experiment. We determined the effects of surfactants and their concentration, the stirring time, the precipitation temperature, the stirring intensity, the drug concentration and the volume ratio of antisolvent to solvent on the mean particle size (MPS) of the AmB nanoparticles. Increased stirring intensity and precipitation time favored AmB nanoparticles with smaller MPS, but precipitation times exceeding 30 min did not further reduce the MPS. Increased Tween-80 concentration and the drug concentration decreased the MPS of the AmB nanoparticles. Increased precipitation temperature and antisolvent to solvent volume ratio initially decreased the MPS of the AmB nanoparticles, which increased thereafter. Optimum conditions produced AmB nanoparticles with an MPS of 135.1 nm. The AmB nanoparticles were characterized through scanning electron microscopy (SEM), mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TG), solvent residue, drug purity test, and dissolution testing. The analyses indicated that the chemical structure of AmB remained unchanged in the nanoparticles, but the structure was changed from crystalline to amorphous. The residual DMSO in the nanoparticles was 0.24% less than the standard set by the International Conference on Harmonization limit for class III solvents. The AmB nanoparticles exhibited 2.1 times faster dissolution rates and 13 times equilibrium solubility compared with the raw drug. The detection results indicate that the AmB nanoparticles potentially improved the oral absorption of AmB. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca.

    Science.gov (United States)

    Riba, Jordi; McIlhenny, Ethan H; Valle, Marta; Bouso, José Carlos; Barker, Steven A

    2012-01-01

    Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT(2A/1A/2C) agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; Krockenberger, M B; Kimble, B; Govendir, M

    2014-02-01

    Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h. © 2013 John Wiley & Sons Ltd.

  16. Value of oral effervescent powder administration for multidetector CT evaluation of esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ringe, Kristina I., E-mail: ringe.kristina@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Meyer, Simone, E-mail: Meyer.simone.rad@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Ringe, Bastian P., E-mail: Ringe.bastian@mh-hannover.de [Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Winkler, Michael, E-mail: Winkler.michael@mh-hannover.de [Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Wacker, Frank, E-mail: Wacker.frank@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Raatschen, Hans-Juergen, E-mail: Raatschen.hans-juergen@mh-hannover.de [Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover (Germany)

    2015-02-15

    Highlights: • Oral effervescent powder improves esophageal distension and wall assessment at CT. • This technique improves detection and T staging of esophageal cancer at CT. • It can be easily adopted in clinical routine in patients with esophageal pathology. - Abstract: Purpose: To assess the value of oral effervescent powder (EP) for evaluation of esophageal distension, and for detection and staging of esophageal cancer with contrast-enhanced CT. Materials and methods: 84 patients without esophageal pathology and 52 patients with histological confirmed diagnosis of esophageal cancer were included in this prospective IRB-approved study. Half of the patients in both groups received EP prior to CT. Esophageal distension was assessed by planimetry of the inner (IA) and outer area (OA). Two blinded readers evaluated the datasets separately with regard to diagnosis of esophageal cancer (yes/no) and staging (T0-T4), if applicable. Distension results were compared (t-Test). In patients with cancer sensitivity, specificity, NPV and PPV were calculated. CT staging results were compared to histopathology (Cohen-k). Results: IA and IA/OA were significantly larger after EP as compared to the group without EP (p < 0.05). Sensitivity, specificity, NPV and PPV for cancer detection cancer were as follows: 78%/78%, 98%/98%, 95%/95%, 87%/87% with EP; 60%/68%, 98%/98%, 94%/94%, 80%/83% without EP. Staging with EP was good (k = 0.84/0.67) and moderate without EP (k = 0.58/0.59). Conclusions: Administration of EP prior to CT results in good distension of the esophagus, and improves detection and staging of esophageal cancer, as compared to control studies without EP.

  17. Secondary and multiple primary cancers relating radiation therapy for cancer of the oral region

    International Nuclear Information System (INIS)

    Horiuchi, Junichi; Shibuya, Hitoshi; Takeda, Masamune; Takagi, Minoru.

    1985-01-01

    Secondary and multiple primary cancers relating radiation therapy for squamous cell carcinoma (s.c.c.) of the oral region including lip, oral cavity and oropharynx were analyzed. Out of 1,197 patients with s.c.c. treated with radiation during about 30 years from 1955 to 1983 June, 56 patients (4.7 %) were regarded as double or multiple cancer. The multiple cancer (s.c.c.) was observed frequently in the multicentric zone such as hypopharynx, esophagus and bronchus as well as in other sites of the oral cavity; 67.7 % (42 out of 62 sites). Frequency of synchronous double cancers was increased in recent ten years; 47.1 % (16/34). Careful examination to the above mentioned multicentric zone leads to early detection of secondary cancer and could be expected cure of the disease. Although possibility of radiation-induced cancer could not be ruled out as for 17 patients with late recurrence (more than 8 years), different histologic diagnosis from s.c.c. was obtained in only one (malignant fibrous histiocytoma). Therefore, it was difficult to discriminate radiation-induced cancer from late recurrence in the present study. (author)

  18. 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)

  19. Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis

    DEFF Research Database (Denmark)

    Dan, Anne E B; Thygesen, Torben H; Pinholt, Else M

    2010-01-01

    was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease...... toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis......, and adrenal suppression was seen. There were no reports of decreased healing. CONCLUSION: These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects....

  20. Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Hansen, Marianne

    2014-01-01

    A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration...

  1. Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Maaike van Putten

    2014-01-01

    Full Text Available Antisense oligonucleotides (AONs used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate.

  2. Oral Administration of Heat-Killed Lactobacillus gasseri OLL2809 Reduces Cedar Pollen Antigen-Induced Peritoneal Eosinophilia in Mice

    Directory of Open Access Journals (Sweden)

    Toshihiro Sashihara

    2008-01-01

    Conclusions: We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

  3. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  4. TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

    Science.gov (United States)

    TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.The relationship o...

  5. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Hui-fang [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Takaoka, Munenori [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Bao, Xiao-hong [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Wang, Zhi-gang [College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Hohhot 010021 (China); Tomono, Yasuko [Division of Molecular and Cell Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 700-0202 (Japan); Sakurama, Kazufumi; Ohara, Toshiaki [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Fukazawa, Takuya; Yamatsuji, Tomoki [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Fujiwara, Toshiyoshi [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Naomoto, Yoshio, E-mail: ynaomoto@med.kawasaki-m.ac.jp [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

  6. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    International Nuclear Information System (INIS)

    Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong; Wang, Zhi-gang; Tomono, Yasuko; Sakurama, Kazufumi; Ohara, Toshiaki; Fukazawa, Takuya; Yamatsuji, Tomoki; Fujiwara, Toshiyoshi; Naomoto, Yoshio

    2012-01-01

    Highlights: ► A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. ► TAE226 suppressed proliferation and migration, with a modest effect on adhesion. ► Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. ► TAE226 treatment suppressed the progression of peritoneal dissemination. ► Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable

  7. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

    Science.gov (United States)

    Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

    2005-09-01

    Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients

  8. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

    Directory of Open Access Journals (Sweden)

    Alvaro eGarcía-Aviles

    2015-03-01

    Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

  9. Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine.

    Science.gov (United States)

    Favazza, A; Motanaro, D; Messa, P; Antonucci, F; Gropuzzo, M; Mioni, G

    1992-01-01

    The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    Science.gov (United States)

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

  11. The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

    Directory of Open Access Journals (Sweden)

    Temitayo O. Iji

    2013-11-01

    Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

  12. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

  13. Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in dog plasma and its application to their pharmacokinetic study after oral administration of tripterygium glycosides tablets.

    Science.gov (United States)

    Su, Meng-xiang; Song, Min; Yang, Da-song; Shi, Jin-fang; Di, Bin; Hang, Tai-jun

    2015-05-15

    A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Core/shell cellulose-based microspheres for oral administration of Ketoprofen Lysinate.

    Science.gov (United States)

    Guarino, Vincenzo; Caputo, Tania; Calcagnile, Paola; Altobelli, Rosaria; Demitri, Christian; Ambrosio, Luigi

    2018-01-26

    Herein, we propose the fabrication of a new carrier with core/shell structure-inner core of cellulose acetate (CA) coated by a micrometric layer of chitosan (CS)-fabricated through an integrated process, which combines Electro Dynamic Atomization (EDA) and layer-by-layer (LbL) technique. We demonstrate that CA based microspheres possess a unique capability to relevantly retain the drugs-that is, Ketoprofen Lysinate (KL)-along the gastric tract, while providing a massive release along the intestine. CS shell slightly influences the morphology and water retention under different pH conditions, improving drug encapsulation without compromising drug release kinetics. In vitro studies in simulated gastric and intestine fluids (SGF, SIF) with physiological enzymes, show a moderate release of LSK during the first 2 h (ca. 20% at pH 2), followed by a sustained release during the next 6 h (ca. 80% at pH 7). The obtained results demonstrate that CA-based microspheres hold strong potential to be used as carriers for a delayed oral administration of anti-inflammatory drugs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  15. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits

    Science.gov (United States)

    Pavithra, B. H.; Jayakumar, K.

    2009-01-01

    Investigation was carried out in adult New Zealand white rabbits to study the influence of curcumin pre-treatment on pharmacokinetic disposition of norfloxacin following single oral administration. Sixteen rabbits were divided into two groups of eight each consisting of either sex. Animals in group-I were administered norfloxacin (100 mg/kg body weight p.o), while animals in group-II received similar dose of norfloxacin after pre-treatment with curcumin (60 mg/kg body weight per day, 3 days, p.o). Blood samples were drawn from the marginal ear vein into heparin-coated vials at 0 (zero time), 5, 10, 15, 30 min and 1, 2, 4, 6, 12 and 24 h post-treatment. Plasma norfloxacin concentrations were determined by high performance liquid chromatography. The plasma concentration-time profile of norfloxacin was adequately described by a one-compartment open model. The pharmacokinetic data revealed that curcumin-treated animals had significantly (p ≤ 0.05) higher area under the plasma concentration-time curve and area under the first moment of plasma drug concentration-time curve. Prior treatment of curcumin significantly (p ≤ 0.05) increased elimination half-life and volume of distribution of norfloxacin. Further treatment with curcumin reduced loading and maintenance doses by 26% and 24% respectively. PMID:19934593

  16. Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Kano

    2016-08-01

    Full Text Available The protective effect of isoflavones on skin damage from ultraviolet (UV radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05. The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05. Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05. Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05. These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice.

  17. Absorption, Distribution, Metabolism and Excretion of 3-MCPD 1-Monopalmitate after Oral Administration in Rats.

    Science.gov (United States)

    Gao, Boyan; Liu, Man; Huang, Guoren; Zhang, Zhongfei; Zhao, Yue; Wang, Thomas T Y; Zhang, Yaqiong; Liu, Jie; Yu, Liangli

    2017-03-29

    Fatty acid esters of monochloropropane 1,2-diol (3-MCPD) are processing-induced toxicants and have been detected in several food categories. This study investigated the absorption, distribution, metabolism, and excretion of 3-MCPD esters in Sprague-Dawley (SD) rats using 3-MCPD 1-monopalmitate as the probe compound. The kinetics of 3-MCPD 1-monopalmitate in plasma was investigated using SD rats, and the results indicated that 3-MCPD 1-monopalmitate was absorbed directly in vivo and metabolized. Its primary metabolites in the liver, kidney, testis, brain, plasma, and urine were tentatively identified and measured at 6, 12, 24, and 48 h after oral administration. Structures were proposed for eight metabolites. 3-MCPD 1-monopalmitate was converted to free 3-MCPD, which formed the phase II metabolites. All of the metabolites were chlorine-related chemical components; most of them existed in urine, reflecting the excretion pattern of 3-MCPD esters. Understanding the metabolism of 3-MCPD esters in vivo is critical for assessing their toxicities.

  18. Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses.

    Science.gov (United States)

    Kuroda, Taisuke; Nagata, Shun-ichi; Takizawa, Yoshimasa; Tamura, Norihisa; Kusano, Kanichi; Mizobe, Fumiaki; Hariu, Kazuhisa

    2013-08-01

    The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW) resulted in a bioavailability of 38%, which induced a peak plasma drug concentration at 1h and a maximal inhibition of wheal formation (39%) at 2h. A pharmacokinetic/pharmacodynamic link model showed that CPM in horses has lower efficacy, much lower potency and slightly lower sensitivity than other reported antihistamines. These results indicated that CPM should be administered at frequent intervals or at large dose rates to maintain therapeutic concentrations in horses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Administrative Challenges to the Integration of Oral Health With Primary Care: A SWOT Analysis of Health Care Executives at Federally Qualified Health Centers.

    Science.gov (United States)

    Norwood, Connor W; Maxey, Hannah L; Randolph, Courtney; Gano, Laura; Kochhar, Komal

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce.

  20. Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

    Science.gov (United States)

    Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

    2018-06-01

    Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

  1. Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

    International Nuclear Information System (INIS)

    Draganov, Dragomir I.; Markham, Dan A.; Beyer, Dieter; Waechter, John M.; Dimond, Stephen S.; Budinsky, Robert A.; Shiotsuka, Ronald N.; Snyder, Stephanie A.; Ehman, Kimberly D.; Hentges, Steven G.

    2015-01-01

    Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of 3 H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total 3 H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of 3 H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC–MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection

  2. Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

    Science.gov (United States)

    He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

    2015-04-22

    Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright

  3. Oral Lesion as Unusual First Manifestation of Multiple Myeloma: Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    A. Romano

    2014-01-01

    Full Text Available Extramedullary plasmacytoma (EMP and solitary bone plasmacytoma (SBP represent a disease continuum through a multistage process of cell differentiation, survival, proliferation, and dissemination, strictly related to multiple myeloma (MM, the second most common hematological malignancy. Herein, we report two cases of recurrent oral plasmacytoma progressed to MM, in which the first clinical sign of a more widespread disease was limited to the mouth. Based on our experience, we recommend a strict workup for the differential diagnosis between EMP, SBP, and MM for patients with oral plasmacytoma, including radiological exam of the skeleton, magnetic resonance imaging (MRI of the bone, and positive emission tomography (FDG-PET. MRI and possibly PET can all be used to more sensitively detect EM plasmacytoma sites.

  4. Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2016-10-01

    Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

  5. The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

    International Nuclear Information System (INIS)

    Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

    2005-01-01

    In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

  6. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  7. The Effects of Fat-soluble Vitamin Administration on Plasma Vitamin Status of Nursing Pigs Differ When Provided by Oral Administration or Injection

    Directory of Open Access Journals (Sweden)

    Y. D. Jang

    2014-05-01

    Full Text Available Four experiments were conducted to investigate the effect of fat-soluble vitamin administration to sows or newborn pigs on plasma vitamin status. In Exp. 1 and 2, a total of 24 and 43 newborn pigs were allotted to control and vitamin treatments (vitamin D3 with variable addition of vitamins A and E orally or by i.m. injection. In Exp. 3, pigs from Exp. 2 were allotted to 2 treatments (±vitamins D3 and E in drinking water for 14 d postweaning. In Exp. 4, twenty-four gestating sows were used for 2 treatments (±injection of a vitamin D3/A/E product 2 wk prepartum. In Exp. 1 and 2, when vitamin D3 was administrated orally or by i.m. injection on d 1 of age, pigs had increased plasma 25-hydroxycholecalciferol (25-OH D3 concentration 10 d after administration compared with control pigs (p<0.05. The injectable administration with vitamin D3 and E was able to achieve higher plasma 25-OH D3 (p<0.05 and α-tocopherol (p<0.05 concentrations than oral administration. At weaning, the pigs in the injection group had higher plasma 25-OH D3 concentration than those in the other groups in both studies (p<0.05. In Exp. 3, water supplementation of vitamin D3 and E postweaning increased plasma 25-OH D3 and α-tocopherol concentrations at d 14 postweaning (p<0.01. In Exp. 4, when sows were injected with the vitamin D3 product prepartum, serum 25-OH D3 concentrations of sows at farrowing (p<0.01, and in their progeny at birth (p<0.01 and weaning (p<0.05 were increased. These results demonstrated that fat-soluble vitamin administration to newborn pigs increased plasma 25-OH D3 concentration regardless of administration routes and α-tocopherol concentration by the injectable route, and that water supplementation of vitamin D3 and E to nursery pigs increased plasma 25-OH D3 and α-tocopherol concentrations. Additionally, injecting sows with vitamin D3 prepartum increased 25-OH D3 in sows and their offspring. If continued research demonstrates that the serum levels of

  8. Oral administration of sitagliptin activates CREB and is neuroprotective in murine model of brain trauma

    Directory of Open Access Journals (Sweden)

    Brian Dellavalle

    2016-12-01

    Full Text Available Introduction: Traumatic brain injury is a major cause of mortality and morbidity. We have previously shown that the injectable glucagon-like peptide-1 (GLP-1 analogue, liraglutide, significantly improved the outcome in mice after severe traumatic brain injury (TBI. In this study we are interested in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream. This class has yet to be investigated as a potential therapy for TBI. Methods: Mice were administrated once-daily 50 mg/kg of sitagliptin in a Nutella® ball or Nutella® alone throughout the study, beginning two days before severe trauma was induced with a stereotactic cryo-lesion. At two days post trauma, lesion size was determined. Brains were isolated for immunoblotting for assessment of selected biomarkers for pathology and protection.Results: Sitagliptin treatment reduced lesion size at day 2 post-injury by ~28% (p0.05. Conversely, apoptotic tone (alpha-spectrin fragmentation, Bcl-2 levels and the neuroinflammatory markers IL-6, and Iba-1 were not affected by treatment.Conclusions: This study shows, for the first time, that DPP-IV inhibition ameliorates both anatomical and biochemical consequences of TBI and activates CREB in the brain. Moreover, this work supports previous studies suggesting that the effect of GLP-1 analogues in models of brain damage relates to GLP-1 receptor stimulation in a dose-dependent manner.Keywords: GLP-1, Traumatic Brain Injury, TBI, sitagliptin, liraglutide, CREB, Oxidative Stress, GIP, DPP-IV, DPP-4

  9. Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats.

    Science.gov (United States)

    Pozzi, C R; Corrêa, B; Xavier, J G; Direito, G M; Orsi, R B; Matarazzo, S V

    2001-01-01

    The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly.

  10. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.

    Science.gov (United States)

    Fujita, Mitsugu; Ohnishi, Katsunori; Takaoka, Shinsaku; Ogasawara, Kazuya; Fukuyama, Ryo; Nakamuta, Hiromichi

    2011-01-01

    To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

  11. Oral gadopentetate dimeglumine administration as a negative gastrointestinal contrast agent to improve image quality of MR cholangiopancreatography

    International Nuclear Information System (INIS)

    Chen Yi; Xu Yikai; Zhao Yuhui; Wang Guisheng

    2008-01-01

    Objective: To choose optimal concentration and volume of Gd-DTPA solution as a oral gastrointestinal negative contrast agent for MRCP. To evaluate the role of Gd-DTPA solution in improving image quality of MRCP. Methods: In vitro experiment: Gd-DTPA solution was made with different concentrations. T 1 WI, T 2 WI, two-dimensional single slice fast spin echo sequence and three-dimensional half-fourier acquisition single-shot fast spin echo sequence were performed to measure the signal intensity of these contrast agents respectively, so Gd-DTPA solution with the optimal concentration can be decided as oral negative gastrointestinal contrast agent on MRCP. Clinical study: The Gd-DTPA solution with optimal concentration and volume was regarded as an oral negative gastrointestinal contrast agent of MRCP. Twenty- four' patients were performed with MRCP before and after (5-10 minutes and 10-15 minutes) administration of oral negative gastrointestinal contrast agent and image quality was analyzed. Statistical analysis was performed using analysis of variance with SPSS 10.0. Results: When the concentration of Gd-DTPA solution was ≤0.01 mol/L, the contrast agent was hyperintense on T 1 WI. On T 2 WI, when the concentration was ≥0.015 mol/L, it was as hypointense as basic ground; On 2D FSE MRCP images, controls were hyperintense and the contrast agent with concentration ranging from 0.0025 mol/L to 0.03 mol/L was hypointense. On 3D HEAST MRCP image, controls were hyperintense and when the concentration of Gd-DTPA was ≥0.01 mol, the contrast agent was hypointense. The Gd-DTPA solution with the concentration of 0.01 mol/L and the volume of 100 ml was chosen as MRCP oral negative gastrointestinal contrast agent. On MRCP images after oral administration of the contrast agent, in 10-15 minutes, the average grade scores within 24 patients of the intrahepatic bile duct, the common hepatic bile duct, the gall bladder, the common bile duct and pancreatic duct (the average grade

  12. 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.

  13. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

    Science.gov (United States)

    Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

    2013-10-01

    The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  14. Recovery Effects of Oral Administration of Glucosylceramide and Beet Extract on Skin Barrier Destruction by UVB in Hairless Mice

    Directory of Open Access Journals (Sweden)

    Yoshihiro Tokudome

    2017-10-01

    Full Text Available Purified glucosylceramide from beet extract (beet GlcCer and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.

  15. An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug

    Directory of Open Access Journals (Sweden)

    Munsell M

    2016-12-01

    Full Text Available Michael Munsell,1 Molly Frean,1 Joseph Menzin,1 Amy L Phillips2 1Boston Health Economics, Inc., Waltham, MA, USA; 2Health Economics & Outcomes Research, EMD Serono Inc., Rockland, MA, USA Objective: As the multiple sclerosis (MS disease-modifying drug (DMD treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. Methods: This retrospective database study used IMS Health Real World Data Adjudicated Claims – US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR, calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8 versus nonadherence (MPR <0.8 to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral. Covariates included patient baseline characteristics (ie, age, sex, comorbidities and index DMD type. Results: The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8 did not differ significantly between the self-injectable (54.1% and the oral DMD cohorts (53.0%; P=0.5075. After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937–1.202; P=0.3473. Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085–1.335; P=0.0005 and age groups older than 18–34 years (ORs 1.220–1.331; P<0.01. Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511–0.747; P<0.0001. Conclusion: Male

  16. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  17. Développement et évaluation de nanoparticules bioadhésives pour l'administration orale de petides

    OpenAIRE

    Hecq, Julien

    2017-01-01

    Ces dernières années, le nombre d’agents thérapeutiques issus des biotechnologies n’a cessé d’augmenter. Parmi ceux-ci, plus de 85% sont administrés par voie parentérale, principalement par injection sous-cutanée ou intraveineuse. Cette forme d’administration ne favorisant pas la compliance des patients, de nombreuses recherches ont été effectuées afin de trouver des alternatives à ces voies invasives, telles que la voie intranasale, pulmonaire, transdermique ou orale. Cette dernière a pour a...

  18. Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

    International Nuclear Information System (INIS)

    Gulyas, Balazs; Halldin, Christer; Sandell, Johan; Farde, Lars; Sovago, Judit; Cselenyi, Zsolt; Vas, Adam; Kiss, Bela; Karpati, Egon

    2002-01-01

    Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [ 11 C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [ 11 C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [ 11 C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

  19. Effects of long-term light, darkness and oral administration of melatonin on serum levels of melatonin

    OpenAIRE

    Naser Farhadi; Majid Gharghani; Zahra Farhadi

    2016-01-01

    Background: Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Methods: Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to...

  20. Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

    Science.gov (United States)

    Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

    2002-08-01

    Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

  1. Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

    Energy Technology Data Exchange (ETDEWEB)

    Gulyas, Balazs [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm (Sweden); Halldin, Christer; Sandell, Johan; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Sovago, Judit; Cselenyi, Zsolt [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Vas, Adam; Kiss, Bela; Karpati, Egon [Chemical Works of Gedeon Richter Ltd., Budapest (Hungary)

    2002-08-01

    Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [{sup 11}C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [{sup 11}C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [{sup 11}C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and

  2. Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model

    OpenAIRE

    Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

    2013-01-01

    Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and ...

  3. Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

    Science.gov (United States)

    Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

    2018-03-21

    Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

  4. The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

    Science.gov (United States)

    Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

    2010-02-01

    The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

  5. Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

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    Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

  6. In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

    Science.gov (United States)

    Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

    2017-08-30

    The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

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    Liqian Wang

    2017-06-01

    Full Text Available Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.. Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water and solution B (acetonitrile at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well.

  8. Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

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    Yan Du

    2017-09-01

    Full Text Available A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS, butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C18 column (1.8 μm, 2.1 mm × 50 mm with a gradient system consisting of solution A (0.1% acetic acid in water and solution B (methanol at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats.

  9. Oral Administration of (S)-Allyl-l-Cysteine and Aged Garlic Extract to Rats: Determination of Metabolites and Their Pharmacokinetics.

    Science.gov (United States)

    Park, Taehoon; Oh, Ju-Hee; Lee, Joo Hyun; Park, Sang Cheol; Jang, Young Pyo; Lee, Young-Joo

    2017-11-01

    ( S )-Allyl-l-cysteine is the major bioactive compound in garlic. ( S )-Allyl-l-cysteine is metabolized to ( S )-allyl-l-cysteine sulfoxide, N -acetyl-( S )-allyl-l-cysteine, and N -acetyl-( S )-allyl-l-cysteine sulfoxide after oral administration. An accurate LC-MS/MS method was developed and validated for the simultaneous quantification of ( S )-allyl-l-cysteine and its metabolites in rat plasma, and the feasibility of using it in pharmacokinetic studies was tested. The analytes were quantified by multiple reaction monitoring using an atmospheric pressure ionization mass spectrometer. Because significant quantitative interference was observed between ( S )-allyl-l-cysteine and N -acetyl-( S )-allyl-l-cysteine as a result of the decomposition of N -acetyl-( S )-allyl-l-cysteine at the detector source, chromatographic separation was required to discriminate ( S )-allyl-l-cysteine and its metabolites on a reversed-phase C 18 analytical column with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile. The calibration curves of ( S )-allyl-l-cysteine, ( S )-allyl-l-cysteine sulfoxide, N -acetyl-( S )-allyl-l-cysteine, and N -acetyl-( S )-allyl-l-cysteine sulfoxide were linear over each concentration range, and the lower limits of quantification were 0.1 µg/mL [( S )-allyl-l-cysteine and N -acetyl-( S )-allyl-l-cysteine] and 0.25 µg/mL [( S )-allyl-l-cysteine sulfoxide and N -acetyl-( S )-allyl-l-cysteine sulfoxide]. Acceptable intraday and inter-day precisions and accuracies were obtained at three concentration levels. The method satisfied the regulatory requirements for matrix effects, recovery, and stability. The validated LC-MS/MS method was successfully used to determine the concentration of ( S )-allyl-l-cysteine and its metabolites in rat plasma samples after the administration of ( S )-allyl-l-cysteine or aged garlic extract. Georg Thieme Verlag KG Stuttgart · New York.

  10. Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction.

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    Wei Ren

    Full Text Available Huang-Lian-Jie-Du Decoction (HLJDD is a classical Traditional Chinese Medicine (TCM formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK and pharmacodynamic (PD data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM method. Additionally, the levels of 7 cytokines (CKs in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, IL-1β, IL-10, and macrophage inflammatory protein-2 (MIP-2 and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that

  11. Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

    Science.gov (United States)

    Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

    2013-05-01

    Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p MDMA ratios in plasma were higher than those in OF (p MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

  12. Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

    Science.gov (United States)

    Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

    2014-07-01

    The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials.

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    Shuo Liu

    Full Text Available Intravenous glucocorticoids are recommended for multiple sclerosis (MS. However, they can be inconvenient and expensive. Due to their convenience and low cost, oral glucocorticoids may be an alternative treatment. Recently, several studies have shown that there is no difference in efficacy and safety between oral methylprednisolone (oMP and intravenous methylprednisolone (ivMP.We sought to assess the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses in this meta-analysis.Randomized controlled trials (RCTs evaluating the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane Library, Medline, EMBASE and China Biology Medicine until October 25, 2016, without language restrictions. The proportion of patients who had improved by day 28 was chosen as the efficacy outcome. We chose the risk ratio (RR to analyze each trial with the 95% confidence interval (95% CI. We also used the fixed-effects model (Mantel-Haenszel approach to calculate the pooled relative effect estimates.A total of 5 trials were identified, which included 369 patients. The results of our meta-analysis revealed that no significant difference existed in relapse improvement at day 28 between oMP and ivMP (RR 0.96, 95% CI 0.84 to 1.10. No evidence of heterogeneity existed among the trials (P = 0.45, I2 = 0%. Both treatments were equally safe and well tolerated except that insomnia was more likely to occur in the oMP group compared to the ivMP group.Our meta-analysis reveals strong evidence that oMP is not inferior to ivMP in increasing the proportion of patients experiencing clinical improvement at day 28. In addition, both routes of administration are equally well tolerated and safe. These findings suggest that we may be able to replace ivMP with oMP to treat MS relapses.

  14. Metal ion-oxytetracycline pharmacokinetic interactions after oral co-administration in broiler chickens.

    Science.gov (United States)

    Ziółkowski, H; Jasiecka, A; Zuśka-Prot, M; Przybysz, J; Grabowski, T; Jaroszewski, J J

    2016-08-01

    The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require

  15. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease

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    Athanassios Fragoulis

    2017-08-01

    Full Text Available Introduction: There is increasing evidence for the involvement of chronic inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD. Nuclear factor erythroid 2-related factor 2 (Nrf2 is an anti-inflammatory transcription factor that regulates the oxidative stress defense. Our previous experiments demonstrated that kavalactones protect neuronal cells against Amyloid β (Aβ-induced oxidative stress in vitro by Nrf2 pathway activation. Here, we tested an in vivo kavalactone treatment in a mouse model of AD. Methods: The kavalactone methysticin was administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Nrf2 pathway activation was measured by methysticin treatment of ARE-luciferase mice, by qPCR of Nrf2-target genes and immunohistochemical detection of Nrf2. Aβ burden was analyzed by CongoRed staining, immunofluorescent detection and ELISA. Neuroinflammation was assessed by immunohistochemical stainings for microglia and astrocytes. Pro-inflammatory cytokines in the hippocampus was determined by Luminex multi-plex assays. The hippocampal oxidative damage was detected by oxyblot technique and immunohistochemical staining against DT3 and 4-HNE. The cognitive ability of mice was evaluated using Morris water maze. Results: Methysticin treatment activated the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of methysticin-treated APP/Psen1 mice was not altered compared to untreated mice. However, methysticin treatment significantly reduced microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. In addition, the oxidative damage of hippocampi from APP/Psen1 mice was reduced by methysticin treatment. Most importantly, methysticin treatment significantly attenuated the long-term memory decline of APP/Psen1 mice. Conclusion: In summary, these findings show that methysticin administration activates the Nrf2 pathway

  16. Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

    Science.gov (United States)

    Pettifor, J. M.; Benson, R.

    1975-01-01

    Reported are case histories of three infants with congenital malformations (including defective formation of the nose and hands) associated with ingestion of oral anticoagulants during the first trimester of pregnancy. (CL)

  17. Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.

    Science.gov (United States)

    Liu, Tao; Lewis, Tamorah; Gauda, Estelle; Gobburu, Jogarao; Ivaturi, Vijay

    2016-08-01

    Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during a randomized control trial in neonates with abstinence syndrome (NAS). A 3-compartment morphine structural PK model after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method with physiological consideration was used to extrapolate a PK profile from adults to pediatrics. The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO). Goodness-of-fit plots along with normalized prediction distribution error and bootstrap method were performed for model evaluation. We successfully extrapolated the PK profile from adults to pediatrics after IV administration. The estimated first-order absorption rate constant and bioavailability were 0.751 hour(-1) and 48.5%, respectively. Model evaluations showed that the model can accurately and precisely describe the observed data. The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies. The integration of the previous population PK knowledge as prior information successfully overcomes the logistic and practical issue in vulnerable neonate population. © 2016, The American College of Clinical Pharmacology.

  18. Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid.

    Science.gov (United States)

    Xu, Gui-li; Li, Hong-liang; He, Jian-chang; Feng, En-fu; Shi, Pan-pan; Liu, Yue-qiong; Liu, Chang-xiao

    2013-08-26

    Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

  20. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  1. Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats

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    Wenhui Wu

    2012-03-01

    Full Text Available Objective: Shark type II collagen (SCII is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca. We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund’s Adjuvant (CFA. Materials and Methods: The onset of rheumatoid arthritis (RA was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg−1d−1, days 14–28, while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg−1d−1, days 14–28, Tripterygium wilfordii polyglycosidium (TWP (10 mg kg−1d−1, days 14–28, and bovine type II collagen from US (US-CII (1 mg kg−1d−1, days 14–28, respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH reaction, the level of interleukins 10 (IL-10 in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII. Results: Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg−1d−1 (SCII 3 and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced. Conclusions: Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral

  2. Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

    Science.gov (United States)

    Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

    2014-07-01

    Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

  3. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

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    Kirsch Lee E

    2009-12-01

    Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

  4. 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.

  5. 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.

  6. The development and validation of oral cancer staging using administrative health data

    International Nuclear Information System (INIS)

    Li-Ting, Chang; Chung-Ho, Chen; Yi-Hsin, Yang; Pei-Shan, Ho

    2014-01-01

    Oral cancer is a major global health problem. The complexity of histological prognosticators in oral cancer makes it difficult to compare the benefits of different treatment regimens. The Taiwanese National Health database provides an opportunity to assess correlations between outcome and treatment protocols and to compare the effects of different treatment regimens. However, the absence of indices of disease severity is a critical problem. The aim of this study was to ascertain how accurately we could assess the severity of oral cancer at the time of initial diagnosis on the basis of variables in a national database. In the cancer registry database of a medical center in Taiwan, we identified 1067 histologically confirmed cases of oral cancer (ICD9 codes 140, 141 and 143–145) that had been first diagnosed and subjected to initial treatment in this hospital. The clinical staging status was considered as the gold standard and we used concordance (C)-statistics to assess the model’s predictive performance. We added the predictors of treatment modality, cancer subsite, and age group to our models. Our final overall model included treatment regimen, site, age, and two interaction terms; namely, interactions between treatment regimen and age and those between treatment regimen, site, and age. In this model, the C-statistics were 0.82–0.84 in male subjects and 0.96–0.99 in female subjects. Of the models stratified by age, the model that considered treatment regimen and site had the highest C-statistics for the interaction term, this value being greater than 0.80 in male subjects and 0.9 in female subjects. In this study, we found that adjusting for sex, age at first diagnosis, oral cancer subsite, and therapy regimen provided the best indicator of severity of oral cancer. Our findings provide a method for assessing cancer severity when information about staging is not available from a national health-related database

  7. 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...

  8. Lipid-based formulations for oral administration of poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

  9. From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2017-01-01

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Hanna M Vesterinen

    Full Text Available To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil as lead candidates for clinical evaluation.We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

  11. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

    Science.gov (United States)

    Warrender-Sparkes, Matthew; Spelman, Tim; Izquierdo, Guillermo; Trojano, Maria; Lugaresi, Alessandra; Grand'Maison, François; Havrdova, Eva; Horakova, Dana; Boz, Cavit; Oreja-Guevara, Celia; Alroughani, Raed; Iuliano, Gerardo; Duquette, Pierre; Girard, Marc; Terzi, Murat; Hupperts, Raymond; Grammond, Pierre; Petersen, Thor; Fernandez-Bolaños, Ricardo; Fiol, Marcela; Pucci, Eugenio; Lechner-Scott, Jeannette; Verheul, Freek; Cristiano, Edgardo; Van Pesch, Vincent; Petkovska-Boskova, Tatjana; Moore, Fraser; Kister, Ilya; Bergamaschi, Roberto; Saladino, Maria Laura; Slee, Mark; Barnett, Michael; Amato, Maria Pia; Shaw, Cameron; Shuey, Neil; Young, Carolyn; Gray, Orla; Kappos, Ludwig; Butzkueven, Helmut; Kalincik, Tomas; Jokubaitis, Vilija

    2016-04-01

    We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, ptreatment compared with other therapies (ptreatment discontinuation. Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications. © The Author(s), 2015.

  12. Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

    1990-05-01

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

  13. Computer versus lecture: a comparison of two methods of teaching oral medication administration in a nursing skills laboratory.

    Science.gov (United States)

    Jeffries, P R

    2001-10-01

    The purpose of this study was to compare the effectiveness of both an interactive, multimedia CD-ROM and a traditional lecture for teaching oral medication administration to nursing students. A randomized pretest/posttest experimental design was used. Forty-two junior baccalaureate nursing students beginning their fundamentals nursing course were recruited for this study at a large university in the midwestern United States. The students ranged in age from 19 to 45. Seventy-three percent reported having average computer skills and experience, while 15% reported poor to below average skills. Two methods were compared for teaching oral medication administration--a scripted lecture with black and white overhead transparencies, in addition to an 18-minute videotape on medication administration, and an interactive, multimedia CD-ROM program, covering the same content. There were no significant (p lecture groups by education or computer skills. Results showed significant differences between the two groups in cognitive gains and student satisfaction (p = .01), with the computer group demonstrating higher student satisfaction and more cognitive gains than the lecture group. The groups were similar in their ability to demonstrate the skill correctly. Importantly, time on task using the CD-ROM was less, with 96% of the learners completing the program in 2 hours or less, compared to 3 hours of class time for the lecture group.

  14. Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

    Science.gov (United States)

    Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

    2017-11-15

    OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

  15. [Variations in hyperbilirrubinemia in low birth weight newborns under phototherapy and continous or discontinous agar oral administration (author's transl)].

    Science.gov (United States)

    Colomer, J; Moya, M; Marco, V; De Paredes, C; Escrivá, F; Vila, R

    1975-06-01

    Therapeutic attitude in hyperbilirrubinemia is always worth because other infrequent complications but not for this, less important. Phototherapy innocuousness, largely demonstrated, fosters its profilactic use at beginning and not only for those babies with serum bilirrubin over 10 mg % in the first day of life. Previously we have reported positive results with agar oral administration without collateral effects. On this grounds we have planned the following experience in a homogenous group of L.B.W.: one group was fed with agar previously to each formula administration; other group received the same amount of agar but divided in only three administrations in 24 hours; the last group received continuous phototherapy for 96 hours with a white cold fluorescent light from a source of 8-Vita-lite lamp of 40 watts with a intensity of 500 foot candle and 30 lumens. All of these babies weighed less than 2.500 g. and were between 10 and 90 percentil of Lubschenko diagram. They were fed with the same formula and same time table with no infusions, rejecting all that presented any type of pathology. Obstetric conditions were basically identical. This population was randomly divided in four groups. 1) Control group with no profilaxis, but with identical bilirrubin andhematocrit determinations. 2) Group with continuous agar oral administration, 125 mg. before each of the seven formula feeding. 3) Group with discontinuous agar administration, 250 mg. before three of the seven formula feeding. 4) Group with continuous phototherapy for 96 hours. These is initial identification of the groups with statistic signification, and after that a quantitative and sequential evolution of bilirrubin is analized in each group.

  16. Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

    DEFF Research Database (Denmark)

    Bruun, Susanne W.; Josefsen, Knud; Tanassi, Julia T

    2016-01-01

    secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally...

  17. Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

    Science.gov (United States)

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

  18. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

    Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

  19. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    Science.gov (United States)

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATIONMichael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  20. Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Carr, Richard D; Deacon, Carolyn F

    2011-01-01

    Context: The incretin effect is responsible for the higher insulin response to oral glucose than to iv glucose at matching glucose levels. It is notknownwhetherthis effect is restricted to glucose only. Objective: The aim of the study was to examine whether insulin and incretin hormone responses ...

  1. Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration.

    Science.gov (United States)

    Newmeyer, Matthew N; Swortwood, Madeleine J; Taylor, Megan E; Abulseoud, Osama A; Woodward, Thomas H; Huestis, Marilyn A

    2017-08-01

    Establishing science-based driving per se blood Δ 9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  2. Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

    Science.gov (United States)

    Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

    2017-12-01

    To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

  3. Oral administration of heat-killed Lactobacillus gasseri OLL2809 reduces cedar pollen antigen-induced peritoneal eosinophilia in Mice.

    Science.gov (United States)

    Sashihara, Toshihiro; Ikegami, Shuji; Sueki, Natsuko; Yamaji, Taketo; Kino, Kohsuke; Taketomo, Naoki; Gotoh, Minoru; Okubo, Kimihiro

    2008-12-01

    Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/IgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

  4. Evaluation of pancreatic lipase activity by simple urine analysis after oral administration of a new iodine-131-labeled triglyceride

    International Nuclear Information System (INIS)

    Kropp, J.; Knapp, F.F. Jr.; Weyenberg, A.; McPherson, D.W.; Ambrose, K.R.; Callahan, A.P.; Bergmann, K. von; Biersack, H.J.

    1994-01-01

    A new iodine-131-labeled triglyceride analogue called ''MIPAG'' [1,2-dipalmitoyl-3-[(15-p-iodophenyl) pentadecan-1-oyl]rac-glycerol] has been prepared in which 15-(p-iodophenyl)pentadecanoic acid (IPPA) is attached to position-3. MIPAG has been developed for the evaluation of pancreatic exocrine function by simple urine analysis and has been evaluated in rats and humans. After oral administration, IPPA is released from the triglyceride by the action of pancreatic lipases followed by intestinal absorption and the principal IPPA metabolite (p-iodobenzoic acid. IBA) is primarily excreted in the urine. Excretion in the urine and feces was evaluated in rats, as well as the biodistribution in various organs over 21 days. Twenty patients without pancreatic disease (normals) and four patients with pancreatic insufficiency were also investigated. Following oral administration of 30 μCi of MIPAG, urine was collected for two successive 24-h periods. Blood samples were drawn and thin-layer chromatographic (TLC) analysis was performed on the serum lipid extracts. Urine from normals contained 44.9%±7.7% and 61.8%±8.4% of the administered activity after 24 and 48 h, respectively. The patients with pancreatic insufficiency excreted 13.1%±5.6% and 18.9%±6.2%, respectively, which was significantly decreased (P<0.001) compared with normals. The TLC profiles showed an increasing proportion of IBA with time. Urine analysis after oral administration of MIPAG thus appears to be an attractive new technique for the evaluation of pancreatic lipase activity by a simple urine analysis. (orig.)

  5. Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine.

    Science.gov (United States)

    de Queiroz-Neto, A; Mataqueiro, M I; Santana, A E; Alessi, A C

    1994-06-01

    The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

  6. Administración de medicamentos por vía oral: Interacciones medicamento - alimento Oral drug administration: drug-food interactions

    Directory of Open Access Journals (Sweden)

    Nélida Barrueco

    2008-03-01

    Full Text Available Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento.Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO. Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration

  7. Pharmacokinetics and Biodistribution of Aurantiamide and Aurantiamide Acetate in Rats after Oral Administration of Portulaca oleracea L. Extracts.

    Science.gov (United States)

    Chen, Lijiang; Liu, Yang; Jia, Dechao; Yang, Jia; Zhao, Jinhua; Chen, Changlan; Liu, Hongsheng; Liang, Xiao

    2016-05-04

    Aurantiamide and aurantiamide acetate are the main active constituents of purslane (Portulaca oleracea L.), an edible plant with various biological activities. In this study, we developed a validated UHPLC-MS/MS method to quantitate the concentrations of aurantiamide and aurantiamide acetate in the plasma and various organ tissues of rat as the basis to study their pharmacological profile and distribution in vivo. Aurantiamide and aurantiamide acetate were rapidly absorbed following oral administration, both achieving a Cmax at around 0.2 h. The extent of their metabolisms also varied among different organ tissues, resulting in about 90% reduction in concentrations 4 h after their administration, thus leaving no long-term accumulation in the tissues. This is the first study to examine the pharmacokinetic and biodistribution of aurantiamide and aurantiamide acetate in rat, and our work may serve as the first step toward the investigation of the underlying mechanisms associated with the biological activity of purslane.

  8. The disposition of 3H-aflatoxin B1 in the rainbow trout (Oncorhynchys mykiss) after oral and intravenous administration

    International Nuclear Information System (INIS)

    Ngethe, S.; Horsberg, T.E.; Ingebrigtsen, K.

    1992-01-01

    The disposition of tritiated aflatoxin B1 in the rainbow trout following oral and intravenous administration was studied over a period of 8 days by means of liquid scintillation counting and whole-body autoradiography. The pattern of distribution together with the quantitative measurements were fairly similar in both groups, indicating a high degree of gastrointestinal absorption. The highest concentrations of radioactivity were observed in the bile, liver, kidney, pyloric caeca, uveal tract of the eye and the olfactory rosette. Substantial amounts of radioactivity were still present in the liver, kidney, olfactory rosette and the mucosa of the pyloric caeca 8 days after administration. A major fraction of this radioactivity was not extractable with certain polar and nonpolar solvents, indicating covalently bound metabolites

  9. Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

    International Nuclear Information System (INIS)

    Haider, S.; Akhtar, N.; Kidwai, I.M.; Haleem, D.J.

    1999-01-01

    L-tryptophan (TRP) is widely used to enhance serotonin mediate brain functions. In the Present study effects of oral administration of TRP (100mg/kg) daily for 5 weeks, were investigated on the food intake, growth rate and brain indole amine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine (5-HT) were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid (5-HIAA) were hot significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration thorough increases brain 5-ht metabolism and turnover but functional responses to 5-ht are not necessarily increases. (author)

  10. Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

    Science.gov (United States)

    Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

    1989-01-01

    We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

  11. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    Science.gov (United States)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  12. Glucoregulatory and order effects on verbal episodic memory in healthy adolescents after oral glucose administration

    OpenAIRE

    Smith, Michael; Foster, Jonathan

    2008-01-01

    The ingestion of oral glucose has been observed to facilitate memory performance in both elderly individuals and in young adults. However, fewer studies have investigated the effect of glucose on memory in children or adolescents. In the present study, the ingestion of a glucose laden drink was observed to enhance verbal episodic memory performance in healthy adolescents under conditions of divided attention, relative to a placebo drink. Further analyses found that this glucose memory facilit...

  13. Improved Oral Bioavailability and Brain Transport of Saquinavir Upon Administration in Novel Nanoemulsion Formulations

    OpenAIRE

    Vyas, Tushar K.; Shahiwala, Aliasgar; Amiji, Mansoor M.

    2007-01-01

    The aim of this investigation was to develop novel oil-in-water (o/w) nanoemulsions containing saquinavir (SQV), an anti-HIV protease inhibitor, for enhanced oral bioavailability and brain disposition. SQV was dissolved in different types of edible oils rich in essential polyunsaturated fatty acids (PUFA) to constitute the internal oil phase of the nanoemulsions. The external phase consisted of surfactants Lipoid®-80 and deoxycholic acid dissolved in water. The nanoemulsions with an average o...

  14. Oral Administration of Sitagliptin Activates CREB and Is Neuroprotective in Murine Model of Brain Trauma

    DEFF Research Database (Denmark)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

    2016-01-01

    in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV) inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream. This class has yet to be investigated...... for immunoblotting for assessment of selected biomarkers for pathology and protection. Results: Sitagliptin treatment reduced lesion size at day 2 post-injury by ~28% (p

  15. Withdrawal times of oxytetracycline and tylosin in eggs of laying hens after oral administration.

    Science.gov (United States)

    Muñoz, Rubén; Cornejo, Javiera; Maddaleno, Aldo; Araya-Jordán, Carolina; Iragüen, Daniela; Pizarro, Nicolás; San Martín, Betty

    2014-06-01

    Antimicrobials administered to laying hens may be distributed into egg white or yolk, indicating the importance of evaluating withdrawal times (WDTs) of the pharmaceutical formulations. In the present study, oxytetracycline and tylosin's WDTs were estimated. The concentration and depletion of these molecules in eggs were linked to their pharmacokinetic and physicochemical properties. Twenty-seven Leghorn hens were used: 12 treated with oxytetracycline, 12 treated with tylosin, and 3 remained as an untreated control group. After completion of therapies, eggs were collected daily and drug concentrations in egg white and yolk were assessed. The yolk was used as the target tissue to evaluate the WDT; the results were 9 and 3 days for oxytetracycline and tylosin, respectively. In particular, oxytetracycline has a good oral bioavailability, a moderate apparent volume of distribution, a molecular weight of 460 g/mol, and is lightly liposoluble. Tylosin, a hydrosoluble compound, with a molecular weight of 916 g/mol, has a low oral bioavailability and a low apparent volume of distribution, too. Present results suggest that the WDTs of the studied antimicrobials are strongly influenced by their oral bioavailability, the distribution, and the molecular weight and solubility, and that these properties also influence the distribution between the egg yolk and white.

  16. The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

    Science.gov (United States)

    Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2017-02-01

    Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

  17. Oral Administration of N-Acetyl-D Glucosamine Polymer Particles Down-Regulates Airway Allergic Responses

    National Research Council Canada - National Science Library

    Shibata, Yoshimi

    2006-01-01

    ... (IL-12, IL-18 and TNFo) that down-regulate allergic immune responses. We also found that administration of chitin particles resulted in less likely induce the production of IL-10 and prostaglandin E2 (PGE2...

  18. Influence of B-Complex Vitamins on the Pharmacokinetics of Ginsenosides Rg1, Rb1, and Ro After Oral Administration.

    Science.gov (United States)

    Zheng, Peihe; Chen, Yinbin; Fu, Yangyang; Wang, Hecheng; Wang, Jia; Zheng, Siwen; Xiao, Shengyuan; Wang, Yingping

    2017-11-01

    After cultivation of ginseng, ginsenosides, which are the major active ingredients of gingeng, were approved for use by the food industry, and began to be used as added functional ingredients to try to improve the quality and price of functional foods. However, the interaction between different types of ginsenosides and nutrients needs further study. We investigated the effect of B-complex vitamins (which are essential nutrients) on the pharmacokinetics of the ginsenosides protopanaxatriol-type saponin Rg 1 , protopanaxadiol-type saponin Rb 1 , and oleanolic acid-type saponin Ro after oral administration. Ginsenosides Rg 1 , Rb 1 , and Ro, with or without B-complex vitamins, respectively, were administered orally to rats to evaluate their pharmacokinetics. The concentration of ginsenosides in plasma was determined by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were fitted using WinNonlin v6.2. After oral coadministration with B-complex vitamins, the area under the concentration-time curve from zero to infinity (AUC 0-∞ ) of ginsenoside Rg 1 was reduced by 70%, that of ginsenoside Rb 1 was reduced by 43%, and that of ginsenoside Ro was reduced by 34%. The AUC 0-∞ of ginsenosides Rg 1 and Rb 1 showed significant differences between different treatments, but the AUC 0-∞ of ginsenoside Ro did not. These results suggest significant ginsenoside-nutrient interactions between ginsenosides Rg 1 , Rb 1 , and B-complex vitamins.

  19. Oral administration of prednisone to control refractory vertigo in Ménière's disease: a pilot study.

    Science.gov (United States)

    Morales-Luckie, Elizabeth; Cornejo-Suarez, Arnulfo; Zaragoza-Contreras, Miguel A; Gonzalez-Perez, Oscar

    2005-09-01

    To establish whether the oral administration of moderate doses of prednisone reduces refractory vertigo in Ménière's disease. Blinded, randomized, controlled trial. Tertiary referral center. Patients with Ménière's disease with limited vertigo control (Class C) and severe disability (Scale 3). Two groups (n = 8 per group) were treated orally with either diphenidol (25 mg/d) plus acetazolamide (250 mg/48 h) (control group), or the same treatment plus prednisone (0.35 mg/kg) daily for 18 weeks (prednisone group). The variables evaluated were the frequency and duration of vertigo, tinnitus, aural fullness, and audiographic parameters. The clinical surveillance was performed for 12 months after prednisone withdrawal. The frequency and duration of vertigo episodes were reduced by 50% and 30%, respectively, by prednisone treatment. Prednisone-treated patients manifested a significant reduction in tinnitus. No changes were observed in aural fullness or hearing. No metabolic or infectious disorders were observed. Oral prednisone helps to control refractory vertigo in Ménière's disease. These preliminary data suggest that prednisone can be a good noninvasive antivertigo management regimen for these patients.

  20. Benefits of oral administration of an electrolyte solution interrupting a prolonged preoperatory fasting period in pediatric patients.

    Science.gov (United States)

    Moyao-García, D; Corrales-Fernández, M A; Blanco-Rodríguez, G; Sánchez-Hernández, E; Nava-Ocampo, A A

    2001-03-01

    The aim of this study was to evaluate the benefits of an oral isosmolar solution of electrolytes (ISE) administered to interrupt a prolonged fasting period in children undergoing an elective surgical procedure under general anesthesia. Forty unpremedicated children aged 3 to 12 years, ASA I, undergoing a surgical procedure requiring general anesthesia were assigned randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight fasting period for milk and solids of at least 8 hours. In group 2, patients under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3 hours before completing the fasting period. After anesthetic induction, blood glucose level (BGL) was quantified, and patients underwent an endoscopic examination to obtain the gastric content to determine the residual gastric volume (RGV) and pH levels. In group 1, the RGV was 0.78 +/- 0.44 mL/kg, pH was 1.75 +/- 0.38, and BGL was 86.4 +/- 14.5. In group 2, the RGV was 0.40 +/- 0.29 mL/kg, pH was 3.18 +/- 0.61, and BGL was 85.1 +/- 12.6. Only RGV and pH were significantly different between groups. A prolonged fasting period interrupted with oral ISE administration resulted in an RGV of low risk, without counterbalancing a potential fasting-induced hypoglycemia.

  1. Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    di Nuzzo L

    2014-05-01

    Full Text Available Luigi di Nuzzo,1 Rosamaria Orlando,2 Carla Nasca,1 Ferdinando Nicoletti1,31Department of Physiology and Pharmacology, Sapienza University of Rome, 2IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, 3IRCCS Neuromed, Pozzilli, ItalyAbstract: New oral drugs have considerably enriched the therapeutic armamentarium for the treatment of multiple sclerosis. This review focuses on the molecular pharmacodynamics of fingolimod, dimethyl fumarate (BG-12, laquinimod, and teriflunomide. We specifically comment on the action of these drugs at three levels: 1 the regulation of the immune system; 2 the permeability of the blood–brain barrier; and 3 the central nervous system. Fingolimod phosphate (the active metabolite of fingolimod has a unique mechanism of action and represents the first ligand of G-protein-coupled receptors (sphingosine-1-phosphate receptors active in the treatment of multiple sclerosis. Dimethyl fumarate activates the nuclear factor (erythroid-derived 2-related factor 2 pathway of cell defense as a result of an initial depletion of reduced glutathione. We discuss how this mechanism lies on the border between cell protection and toxicity. Laquinimod has multiple (but less defined mechanisms of action, which make the drug slightly more effective on disability progression than on annualized relapse rate in clinical studies. Teriflunomide acts as a specific inhibitor of the de novo pyrimidine biosynthesis. We also discuss new unexpected mechanisms of these drugs, such as the induction of brain-derived neurotrophic factor by fingolimod and the possibility that laquinimod and teriflunomide regulate the kynurenine pathway of tryptophan metabolism.Keywords: demyelinating diseases, pharmacotherapy, fingolimod, dimethyl fumarate, laquinimod, teriflunomide

  2. Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

    Science.gov (United States)

    Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

    2017-10-01

    Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

    Science.gov (United States)

    Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

    2018-02-01

    The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

  4. Beneficial Effects of Long-Term Administration of an Oral Formulation of Angiotensin-(1–7 in Infarcted Rats

    Directory of Open Access Journals (Sweden)

    Fúlvia D. Marques

    2012-01-01

    Full Text Available In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang-(1–7 in hydroxypropyl β-cyclodextrin (HPβCD, in infarcted rats. Myocardial infarction (MI was induced by left coronary artery occlusion. HPβCD/Ang-(1–7 was administered for 60 days (76 μg/Kg/once a day/gavage starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1–7 administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1–7 and indicate HPβCD/Ang-(1–7 as a feasible formulation for long-term oral administration of this heptapeptide.

  5. Epstein-Barr virus in oral shedding of children with multiple sclerosis

    Science.gov (United States)

    Yea, Carmen; Tellier, Raymond; Chong, Patrick; Westmacott, Garrett; Marrie, Ruth Ann; Bar-Or, Amit

    2013-01-01

    Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS). Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry. Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS. Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV. PMID:24014504

  6. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...

  7. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

    2012-01-01

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

  8. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

    DEFF Research Database (Denmark)

    O'Connor, P; Comi, G; Montalban, X

    2009-01-01

    OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, pla...

  9. Comparative pharmacokinetic profiles of tectorigenin in rat plasma by UPLC-MS/MS after oral administration of Iris tectorum Maxim extract and pure tectoridin.

    Science.gov (United States)

    Yang, Min; Yang, Xiaolin; An, Jinmeng; Xiao, Wei; Wang, Zhenzhong; Huang, Wenzhe; Yang, Zhonglin; Li, Fei

    2015-10-10

    Iris tectorum Maxim, a well-known herb medicine, is commonly used for treatment of inflammation, cough, and pharyngitis for a long time in China. Tectoridin, main active ingredient of Iris tectorum Maxim, is often used for its quality control. This study was aimed to analyze the pharmacokinetic profile of tectorigenin (the metabolite of tectoridin) after oral administration of I. tectorum Maxim extract, and to compare the pharmacokinetic characterization of tectorigenin after oral administration of I. tectorum Maxim extract (ITME) and pure tectoridin (PT) in rats. In addition, a simple, reliable and sensitive UPLC-MS/MS method was developed for determination of tectorigenin in rat plasma, using kaempferol as internal standard. The processed samples were separated on a Poroshell 120 SB-C₁₈ column and detected by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The method validation results indicated that the established method was simple, specific and reliable. The pharmacokinetic results showed that the plasma concentration of tectorigenin in ITME group was much higher than that of the PT group (p<0.01). Moreover, compared to PT group, t₁/₂ value and AUC(0-∞) value were also notably increased in ITME group (p<0.01). In conclusion, potential interaction exists between those chemical components in ITME, and the co-existing components in ITME could notably promote the absorption of tectoridin in rats, however, the exact compound(s) which enhance the absorption of tectoridin should be investigated in future study. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Impact of oral meloxicam administration before and after band castration on feedlot performance and behavioral response in weanling beef bulls.

    Science.gov (United States)

    Repenning, P E; Ahola, J K; Callan, R J; French, J T; Giles, R L; Bigler, B J; Coetzee, J F; Wulf, L W; Peel, R K; Whittier, J C; Fox, J T; Engle, T E

    2013-10-01

    Two experiments evaluated the effects of band castration and oral administration of an analgesic in association with castration on performance and behavioral and physiological responses in yearling beef bulls. In Exp. 1 Angus and Charolais-crossbred bull calves (n = 127; 309.8 ± 59.04 kg BW) and in Exp. 2 Hereford, Angus, and Hereford × Angus crossbred bulls (n = 30; 300.8 ± 4.96 kg BW) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) band castration (BAND), 2) band castration with oral administration of meloxicam (BAND-MEL), and 3) sham castration (SHAM). The BAND and SHAM procedures were completed on d 0. The SHAM treatment consisted of all animal manipulations associated with band castration without band application. Meloxicam was administered on d -1, 0, and 1 (1.0, 0.5, and 0.5 mg/kg, respectively) via an oral bolus. Body weight and a subjective chute score (CS) were collected on d -1, 0, 1, 7, 14, and 21 (d 28 Exp. 1 only). In Exp. 2, jugular blood samples were collected immediately before castration and 24 h postcastration for substance P (SP) analysis. In Exp. 2, video documentation on d 0 was used to determine range of vertical head motion (DIST) on a subset of animals during treatment administration. In both experiments, ADG was similar (P ≥ 0.50) between BAND and BAND-MEL, but ADG in SHAM cattle was greater (P castrates in Exp. 1 and 2, respectively. In Exp. 1, CS did not differ (P ≥ 0.26) between BAND and BAND-MEL on any day, but castrates exhibited less desirable CS on d 1 and 28 than SHAM cattle. In Exp. 2, CS was not affected (P ≥ 0.41) by castration or the presence of meloxicam. In Exp. 2, DIST did not differ (P = 0.57) between BAND and BAND-MEL, but when pooled, castrates exhibited greater (P = 0.04) DIST than SHAM. In Exp. 2, plasma SP concentrations were similar between BAND and BAND-MEL (P = 0.81) and between castrates vs. sham cattle (P = 0.67). Results indicate no impact of meloxicam administration on performance

  11. [Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

    Science.gov (United States)

    Morales-León, Felipe; von Plessing-Rossel, Carlos; Villa-Zapata, Lorenzo; Fernández-Rocca, Pola; Sanhueza-Sanhueza, Cindy; Bello-Toledo, Helia; Mella-Montecinos, Sergio

    2015-04-01

    Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

  12. 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...

  13. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

    Directory of Open Access Journals (Sweden)

    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  14. Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice.

    Science.gov (United States)

    Wang, Zhenbin; Wang, Qing; Wang, Lin; Xu, Weidong; He, Yuanqing; Li, Yunliang; He, Song; Ma, Haile

    2017-07-01

    Collagen hydrolysates (CHs) have been demonstrated to have positive effects on skin photoaging by topical application or oral ingestion. However, there has been little research on their influence on skin chronological aging. In this study, 9-month-old female ICR mice were given normal AIN-93M diets containing CHs (2.5, 5 and 10% w/w) from Nile tilapia scale. After 6 months, the collagen content and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities increased significantly (P skin did not change (P > 0.05). The color, luster and quantity of hair were obviously ameliorated. Moreover, the structure of epidermis and dermis, the density and distribution of collagen fibers and the ratio of type I to type III collagen were improved in a dose-dependent manner as shown by histochemical staining. Oral ingestion of CHs increased the collagen content and antioxidant enzyme activities and improved the appearance and structure of skin. These results suggest the potential of CHs as an anti-skin-aging ingredient in nutraceuticals or functional foods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  15. Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

    International Nuclear Information System (INIS)

    Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A.

    2002-01-01

    Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronphenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the 10 B(n,a) 7 Li reaction products is very short, 10-14 μm combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of 10 B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced track etch autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the 10 B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration. (author)

  16. Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

    Science.gov (United States)

    Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

    2016-01-01

    Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

  17. The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2017-05-01

    Full Text Available A biodegradable poly(lactic-co-glycolic acid loading atorvastatin calcium (AC nanoparticles (AC-PLGA-NPs were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGA-NPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

  18. Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.

    Directory of Open Access Journals (Sweden)

    Tamhane M

    1997-01-01

    Full Text Available Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex were divided into four groups as follows--Group 1 (n = 15 normal animals; Group II (n = 6 rats administered metoclopramide (1.35 mg/kg; Group III (n = 8 rats given atropine (0.45 mg/kg. These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8 were administered Terminalia chebula (100 mg/kg/day for 15 days orally. Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5% mixed with phenol red (50 mg/100 ml orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01 and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01. Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01. Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.

  19. [Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

    Science.gov (United States)

    Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

    2001-01-01

    The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

  20. Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

    Science.gov (United States)

    Messenger, Kristen M; Hopfensperger, Marie; Knych, Heather K; Papich, Mark G

    2016-04-01

    To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

  1. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

    Directory of Open Access Journals (Sweden)

    Nicholas A Young

    Full Text Available Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

  2. Transabdominal ultrasonography of the small bowel after oral administration of a non-absorbable anechoic solution: Comparison with barium enteroclysis

    Energy Technology Data Exchange (ETDEWEB)

    Cittadini, Giuseppe; Giasotto, Veronica; Garlaschi, Giacomo; De Cicco, Enzo; Gallo, Alessandra; Cittadini, Giorgio

    2001-03-01

    AIM: The aim of this study was to determine if oral administration of a non-absorbable anechoic solution conveys any benefit during abdominal ultrasound (US), with special reference to its accuracy. MATERIALS AND METHODS: Fifty-three adult out-patients scheduled for small bowel barium enema (SBE) were included. The day before SBE all patients underwent abdominal US before and after oral administration of an isotonic non-absorbable electrolyte solution containing polyethylene glycol (PEG-ELS). Sensitivity and specificity were evaluated using SBE as a gold standard. RESULTS: After ingestion of PEG-ELS satisfactory distension of the intestinal lumen was obtained (11-25 mm) with sequential visualization of jejunoileal loops in 30.9 {+-} 17.3 min. In 15 out of 53 cases both US and SBE showed bowel changes characteristic of Crohn's disease. In three out of 53 cases both US and SBE showed neoplasms. In one out of 53 cases US was negative, SBE positive for local nodularity and ulcerations typical of Crohn's disease. In one out of 53 cases US was negative, SBE positive for macronodularity consistent with coeliac disease. In five out of 53 cases US was negative, while SBE was positive for mininodularity expressive of lymphoid hyperplasia. In 28 out of 53 cases both examinations were negative. CONCLUSION: PEG-ELS administration allows a thorough US investigation of the small bowel, with fair sensitivity (72%) and excellent specificity (100%). False negative findings are mainly due to lymphoid hyperplasia, a feature of uncertain significance in adults. Cittadini G. et al.(2001)

  3. Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging

    NARCIS (Netherlands)

    Rest, van de Ondine; Bloemendaal, Mirjam; Heus, De Rianne; Aarts, Esther

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  4. Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

    NARCIS (Netherlands)

    Rest, O. van de; Bloemendaal, M.; Heus, R.A.A. de; Aarts, E.

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  5. Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana).

    Science.gov (United States)

    Divers, Stephen J; Papich, Mark; McBride, Michael; Stedman, Nancy L; Perpinan, David; Koch, Thomas F; Hernandez, Sonia M; Barron, G Heather; Pethel, Melinda; Budsberg, Steven C

    2010-11-01

    To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity. 21 healthy green iguanas (Iguana iguana). To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg). There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues. Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours.

  6. A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

    Science.gov (United States)

    Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

    2018-02-01

    Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

  7. R-Limonene metabolism in humans and metabolite kinetics after oral administration.

    Science.gov (United States)

    Schmidt, Lukas; Göen, Thomas

    2017-03-01

    We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100-130 µg kg -1 bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected. From two subjects, blood samples were drawn up to 5 h after exposure. The parent compound was analysed in blood using headspace GC-MS. The metabolites cis- and trans-carveol (cCAR), perillyl alcohol (POH), perillic acid (PA), limonene-1,2-diol (LMN-1,2-OH), and limonene-8,9-diol (LMN-8,9-OH) were quantified in both blood and urine using GC-PCI-MS/MS. Moreover, GC-PCI-MS full-scan experiments were applied for identification of unknown metabolites in urine. In both matrices, metabolites reached maximum concentrations 1-2 h post-exposure followed by rapid elimination with half-lives of 0.7-2.5 h. In relation to the other metabolites, LMN-1,2-OH was eliminated slowest. Nonetheless, overall renal metabolite elimination was completed within the 24-h observation period. The metabolite amounts excreted via urine corresponded to 0.2 % (cCAR), 0.2 % (tCAR), <0.1 % (POH), 2.0 % (PA), 4.3 % (LMN-1,2-OH), and 32 % (LMN-8,9-OH) of the orally administered dose. GC-PCI-MS full-scan analyses revealed dihydroperillic acid (DHPA) as an additional LMN metabolite. DHPA was estimated to account for 5 % of the orally administered dose. The study revealed that human LMN metabolism proceeds fast and is characterised by oxidation mainly of the exo-cyclic double bond but also of the endo-cyclic double bond and of the methyl side chain. The study results may support the prediction of the metabolism of other terpenes or comparable chemical structures.

  8. Oral Dalfampridine Improves Standing Balance Detected at Static Posturography in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Luca Prosperini

    2014-01-01

    Full Text Available We report a 14-week post-marketing experience on 20 patients with multiple sclerosis (MS who started prolonged-release (PR oral dalfampridine 10 mg twice daily according to European Medicine Agency criteria. They underwent serial static posturography assessments and the dizziness handicap inventory (DHI to investigate whether PR dalfampridine could impact standing balance and self-reported perception of balance. The incidence of accidental falls per person per month was also recorded throughout the study. Eight (40% patients, who had a relevant improvement in walking speed, were defined as treatment responders. They showed a significant improvement of standing balance (with respect to pretreatment assessment when contrasted with 12 (60% nonresponders (F[4,15] = 3.959, P=0.027. No significant changes in DHI score, as well as in its functional, physical, and emotional subscales, were found in both responders and nonresponders at the end of study (all P values are ≥0.2. Treatment response did not affect the incidence of accidental falls. Future studies based on larger sample sizes, and with longer followup, are required to confirm the beneficial effect of PR dalfampridine on standing balance.

  9. The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma.

    Science.gov (United States)

    Breitkreutz, Iris; Podar, Klaus; Figueroa-Vazquez, Vianihuini; Wilhelm, Scott; Hayden, Patrick J; Anderson, Kenneth C; Raab, Marc S

    2018-05-01

    A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM.

  10. Glucoregulatory and order effects on verbal episodic memory in healthy adolescents after oral glucose administration.

    Science.gov (United States)

    Smith, Michael A; Foster, Jonathan K

    2008-10-01

    The ingestion of oral glucose has been observed to facilitate memory performance in both elderly individuals and in young adults. However, fewer studies have investigated the effect of glucose on memory in children or adolescents. In the present study, the ingestion of a glucose laden drink was observed to enhance verbal episodic memory performance in healthy adolescents under conditions of divided attention, relative to a placebo drink. Further analyses found that this glucose memory facilitation effect was observed only in adolescents exhibiting better glucoregulatory efficiency. These findings demonstrate that the glucose memory facilitation effect can be generalised to younger individuals. The importance of controlling for treatment order in within-subjects designs investigating the glucose memory enhancement effect is also discussed.

  11. Sumatriptan (oral route of administration) for acute migraine attacks in adults

    Science.gov (United States)

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Objectives To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during

  12. Stability of three commonly compounded extemporaneous enrofloxacin suspensions for oral administration to exotic animals.

    Science.gov (United States)

    Petritz, Olivia A; Guzman, David Sanchez-Migallon; Wiebe, Valerie J; Papich, Mark G

    2013-07-01

    To evaluate the stability of 3 extemporaneous oral suspensions of enrofloxacin mixed with readily available flavoring vehicles when stored at room temperature (approx 22°C). Evaluation study. 3 commonly compounded oral suspensions of enrofloxacin. On day 0, commercially available enrofloxacin tablets were compounded with a mixture of distilled water and corn syrup (formulation A) or cherry syrup (formulation B) flavoring vehicles to create suspensions with a nominal enrofloxacin concentration of 22.95 mg/mL, and 2.27% enrofloxacin injectable solution was compounded with a liquid sweetener (formulation C) to create a suspension with a nominal enrofloxacin concentration of 11.35 mg/mL. Preparations were stored in amber-colored vials at room temperature for 56 days. For each preparation, the enrofloxacin concentration was evaluated with high-performance liquid chromatography at prespecified intervals during the study. The pH, odor, and consistency for all suspensions were recorded at the start and completion of the study. Relative to the nominal enrofloxacin concentration, the enrofloxacin concentration strength ranged from 95.80% to 100.69% for formulation A, 108.44% to 111.06% for formulation B, and 100.99% to 103.28% for formulation C. A mild pH increase was detected in all 3 suspensions during the study. Results indicated that, when stored in amber-colored vials at room temperature for 56 days, the enrofloxacin concentration strength in all 3 formulations was retained within acceptance criteria of 90% to 110%. Subjectively, cherry syrup flavoring was better at masking the smell and taste of enrofloxacin than were the other mixing vehicles.

  13. Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

    2010-01-31

    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 in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

  14. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max : 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were....... deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P ....05) peak power during first and second Wingate test by 6.4 ± 2.0 and 4.2 ± 1.0%. Neither acute nor 2-week administration of salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol...

  15. High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.

    Science.gov (United States)

    Frank, T; Bitsch, R; Maiwald, J; Stein, G

    2000-06-01

    The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha

  16. Occurrence of doxycycline resistant bacteria in the oral cavity after local administration of doxycycline in patients with periodontal disease

    DEFF Research Database (Denmark)

    Larsen, T

    1991-01-01

    patients with advanced marginal periodontitis were scaled, and one approximal pocket in each patient was additionally treated with locally delivered doxycycline. Microbiological samples were obtained from the test site, a contralateral control site and tongue and tonsils before treatment and 3, 13, 26......Topical antimicrobial treatment is appearing as a means of therapy in patients with advanced periodontal disease. The purpose of the present study was to examine the occurrence of doxycycline resistant bacteria in subgingival plaque and oral cavity after local administration of doxycycline. Five...... and 52 weeks after treatment. The occurrence and morphological distribution of doxycycline resistant bacteria was determined after anaerobic cultivation on enriched tryptic soy agar with and without doxycycline incorporated. At the test site and on tongue and tonsils the percentage of doxycycline...

  17. Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits.

    Science.gov (United States)

    Khan, Adil Mehraj; Rampal, Satyavan; Sood, Naresh Kumar

    2016-03-09

    The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction (p enrofloxacin. The activities of enzymes, glutathione peroxidase and superoxide dismutase, were induced (p enrofloxacin-meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p enrofloxacin and meloxicam. © The Author(s) 2016.

  18. [The comparison of blood levels between peripheral vein and tooth extraction wound after the oral administration of antibiotics (author's transl)].

    Science.gov (United States)

    Hashimoto, T; Ookawa, H; Morishita, M; Takeyasu, K; Shiiki, K; Imoto, T

    1981-06-01

    The oral administration of 300 mg of clindamycin was undertaken on 23 patients, of 500 mg of cefadroxil on 11 patients and of 250 mg of talampicillin on 12 patients, and then tooth extraction was performed under local anesthesia. Blood samples were taken from the extraction wound and the peripheral vein at the same time and assayed by the bioassay method. The blood levels of clindamycin and cefadroxil indicated a similar pattern between the extraction wound and the peripheral vein, but the blood level of talampicillin reached peek level rapider than clindamycin and cefadroxil. The blood levels of the extraction wound were 60 - 80% as compared with the venous blood levels with each antimicrobial agent.

  19. Insecticidal activity of venomous saliva from Rhynocoris fuscipes (Reduviidae against Spodoptera litura and Helicoverpa armigera by microinjection and oral administration

    Directory of Open Access Journals (Sweden)

    K Sahayaraj

    2011-01-01

    Full Text Available Rhynocoris fuscipes is a potential predator of many economically important pests in India. In the present study, its venomous saliva (VS was collected by milking and diluted with HPLC grade water to different concentrations (200, 400, 600, 800 and 1000 ppm. Microinjection of Rhynocoris fuscipes VS was more toxic than its oral administration in Helicoverpa armigera (cotton bollworm and Spodoptera litura (tobacco cutworm. Thus, R. fuscipes VS was found to be toxic to third instar S. litura and H. armigera with respective LD50s of 846.35 and 861.60 ppm/larva at 96 hours after microinjection. The current results showed that VS of Rhynocoris fuscipes caused mortality of H. armigera and S. litura. Active peptides from VS may be isolated, identified and assessed for their impact in order to ascertain how they alter the physiology of these pests, information that could be applicable in pest management programs.

  20. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

  1. Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

    Science.gov (United States)

    Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

    2015-06-01

    Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

  2. Changes in Bioavailability of Omega-3 (DHA through Alpha-Tocopheryl Phosphate Mixture (TPM after Oral Administration in Rats

    Directory of Open Access Journals (Sweden)

    Roksan Libinaki

    2017-09-01

    Full Text Available Benefits of Omega-3 Docosahexaenoic acid (DHA supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM, following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg or low dose (88.6 mg/kg of DHA. TPM was examined at 1:0.1 w/w (low TPM dose and 1:0.5 w/w (high TPM dose. Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL and AUC values (1396.60 and 1560.60 for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns and 50% (p < 0.05 increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90% the LDC control (p = 0.057. This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

  3. The combined effect of laser and oral administration of Iranian propolis extract on skin wound healing in male rats

    Directory of Open Access Journals (Sweden)

    Nematollah Ghaibi

    2015-05-01

    Full Text Available Background: To date, a lot of research has been carried out on the effect of medications and surgical methods on the treatment of wounds, but no ideal achievement has been obtained yet. This study was conducted to investigate the single and combined effect of laser and propolis on skin wound healing in male rats. Methods: 40 Wistar male rats (200-250 g were divided into 4 groups (n= 10. All animals were anesthetized and sterile skin wound was created by surgical scissors. Control group had no treatment, the second group was treated with laser (10 mW, the third group was treated with oral propolis (100 mg /kg; 3 times /day and the forth group was treated with both laser and propolis. The wound healing level was measured based on the wound area and urinary hydroxyproline content. Results: Urinary hydroxyproline content was increased in groups treated with laser, propolis and combined laser and propolis compared to the control group (P<0.01, 0.05 and 0.01, respectively. Also at the end of the treatment period, the wound extent was significantly lower in the laser, propolis, and combined laser and propolis groups than the control (P<0.05, 0.05 and 0.01, respectively. There was no significant difference between treatment groups. Conclusion: Our results showed that oral administration of propolis or low power laser radiation can increase the wound healing rate.

  4. Disposition and metabolism of glyphosate in the Sprague Dawley rat following oral administration

    International Nuclear Information System (INIS)

    Brewster, D.W.; Warren, J.A.; Hopkins, W.E.

    1991-01-01

    Five groups of male SD rats were administered 14 C-labelled glyphosate, (N-[(phosphonomethyl)glycine]) by gavage at a dose level of 10 mg/kg. Animals were killed 2, 6.3, 28, 96 and 168 hours after dosing and the amount of glyphosate-derived material in various organs and excreta were determined. In addition, the metabolic profile in tissues containing > 1% of the administered dose was evaluated. Approximately 93% of the body burden 2 hours after administration was associated with the GI contents and small intestinal tissue. The total body burden 7 days after administration was ∼1% of the dose. Only the kidneys, small intestine, colon, bone, GI contents, residual carcass contained > 1% of the dose 6 hours after administration and the metabolic profiles of these tissues indicated that ∼100% of the body burden was present as unmetabolized parent material. Glyphosate was rapidly eliminated from these tissues with halflives ranging from 20 to 90 hours. A minor metabolite comprising < 0.1% of the dose was detected in the GI contents and colon tissue of 3 animals. Less than 40% of the administered dose was absorbed from the gut and glyphosate was rapidly eliminated from the body with urine and feces being equally important routes of elimination. The whole body halflife was approximately 52 hours. The results from this study indicate that no toxic metabolites of glyphosate were produced, as there was little evidence of metabolism, and essentially 100% of the body burden was parent glyphosate with no significant persistence of accumulated material

  5. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

    Science.gov (United States)

    Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

    2017-03-09

    A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that

  6. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

    Science.gov (United States)

    Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

    2007-03-01

    To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

  7. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

    International Nuclear Information System (INIS)

    Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

    1986-01-01

    RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy

  8. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

    1986-11-01

    RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

  9. Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.

    Science.gov (United States)

    van Dijkhuizen, E H Pieter; Pouw, Juliëtte N; Scheuern, Andrea; Hügle, Boris; Hardt, Sven; Ganser, Gerd; Kümmerle-Deschner, Jasmin Beate; Horneff, Gerd; Holzinger, Dirk; Bulatović Ćalasan, Maja; Wulffraat, Nico M

    2016-01-01

    Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

  10. Proscillaridin activity in portal and peripheral venous blood after oral administration to man

    International Nuclear Information System (INIS)

    Andersson, K.E.; Bergdahl, B.; Dencker, H.; Wettrell, G.; Linkoeping Univ.

    1977-01-01

    The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the 86 Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4h. The mean amount absorbed as active proscillaridin during the first 4h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6h in three patients. The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation. (orig.) [de

  11. The Dipeptide Monoester Prodrugs of Floxuridine and Gemcitabine—Feasibility of Orally Administrable Nucleoside Analogs

    Directory of Open Access Journals (Sweden)

    Yasuhiro Tsume

    2014-01-01

    Full Text Available Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5¢-L-phenylalanyl-l-tyrosyl-floxuridine and 5¢-L-phenylalanyl-L-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents.

  12. Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

    Directory of Open Access Journals (Sweden)

    John E. Fincham

    2010-08-01

    Full Text Available Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

  13. Oral administration of hot water extracts of Chlorella vulgaris increases physical stamina in mice.

    Science.gov (United States)

    An, Hyo-Jin; Choi, Hyun-Myung; Park, Hyeung-Suk; Han, Jae-Gab; Lee, Eun-Hee; Park, Young-Sig; Um, Jae-Young; Hong, Seung-Heon; Kim, Hyung-Min

    2006-01-01

    A unicellular algae, Chlorella vulgaris, was used as a biological response modifier. Although hot water extracts of C. vulgaris (CVE) are thought to augment immune responses, the effect of CVE on fatigue and physical stamina has not been studied. In the present study, we investigated the effect of CVE on forced swimming test and blood biochemical parameters related to fatigue, blood urea nitrogen (BUN), creatine kinase (CK), lactic dehydrogenase (LDH), glucose (Glc), and total protein (TP). CVE (0.05-0.15 g/kg/day) was orally administered to mice. After 7 days, the immobility time was decreased in the 0.1- and 0.15-g/kg CVE-treated groups (179 +/- 8.3 and 175 +/- 2.1 s) in comparison with the control group (223 +/- 5.4 s). In addition, the contents of BUN, CK, and LDH in the blood serum were decreased in the CVE-fed group. However, they had no effect on the elevation of Glc and TP level. The results predict a potential benefit of CVE for enhancing immune function and improving physical stamina. Copyright 2006 S. Karger AG, Basel.

  14. Study of quality and stability of ursodeoxycholic acid formulations for oral pediatric administration.

    Science.gov (United States)

    Santoveña, A; Sánchez-Negrín, E; Charola, L; Llabrés, M; Fariña, J B

    2014-12-30

    This paper describes a rational method of characterizing the biopharmaceutical stability of two oral suspensions of ursodeoxycholic acid (UDCA) used in pediatrics. Because there is no commercial presentation of UDCA that can administer appropriate doses for infants and children, an active pharmaceutical ingredient (API) formulation is required. Due to its very low solubility and low dose in the formula (1.5%), two different suspensions with minimal use of excipients were studied, avoiding the use of complex additives and those not recommended by the European Medicines Agency (EMA). Adherence to Standard Operating Procedure (SOP) allows the preparation of formulations with appropriately sized and stable particles, and suitable rheological behavior in withdrawing the dose after stirring. Dose uniformity, expressed as mass and content variability, was determined using the criteria of the European and the United States Pharmacopoeia. Additionally, dose content variation of every mass determined was studied. A rational method was developed for determining the dose uniformity of UDCA in suspensions, whether freshly prepared or after storage under different conditions for 30 and 60 days. This method permits detection of differences between doses taken at different heights in the vessel at various times and storage conditions. UDCA was stable under all conditions studied, requiring the presence of glycerol in the formulation to obtain the declared API value after stirring. Storage of UDCA suspensions in a refrigerator increased variability between doses. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Transmission of [14C]deoxynivalenol to eggs following oral administration to laying hens

    International Nuclear Information System (INIS)

    Prelusky, D.B.; Trenholm, H.L.; Hamilton, R.M.G.; Miller, J.D.

    1987-01-01

    Following a single oral dose of [ 14 C]deoxynivalenol (2.2 mg of DON, 2.4 μCi/bird) low levels of residues were transmitted to eggs. Maximum radioactivity, which occurred in the first eggs laid after dosing (within 24 h), amounted to 1.9 μg DON-equivalents/60-g egg (0.087% of dose) levels dropped rapidly in ensuing eggs. During daily consumption of DON, administered in spiked feed over a 12-day period (2.2 mg of DON/bird per day for 6 days followed by 2.2 mg of [ 14 C]DON, 1.5 μCi/bird per day for 6 days), radioactivity levels increased with each subsequent egg laid up until the last exposure to the toxin; maximum levels accounted for 4.2 μg DON-equivalents/60-g egg. Residues quickly declined once the birds were switched to clean feed. Results indicate that although residues appear to accumulate in eggs, levels do not persist once the contaminated source is withdrawn. Preliminary analysis of egg material showed only about 10% of radioactivity present could be identified as the parent toxin, DON

  16. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    Directory of Open Access Journals (Sweden)

    Cao-Xin Chen

    2015-01-01

    Full Text Available Cardiotoxin (CTX from Naja naja atra venom (NNAV reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.

  17. Distribution, Metabolism and Toxic Effects of Beta-Cypermethrin in Lizards (Eremias argus) Following Oral Administration.

    Science.gov (United States)

    Chen, Li; Xu, Peng; Diao, Jinling; Di, Shanshan; Li, Ruiting; Zhou, Zhiqiang

    2016-04-05

    Beta-cypermethrin (BCYP), a synthetic pyrethriod (PYR) pesticide which is a mixture of the alpha- and theta- cypermethrin, have been reported various toxicological profiles to non-target organisms. But little is known about assimilation, accumulation and toxic effects of BCYP in reptiles. The present study firstly elucidated absorption, tissue distribution, excretion of BCYP in Eremias argus . Treated group were administered orally with BCYP 20mg/kg body weight (bw) dissolved in corn oil. Neurotoxicity was observed at 24h after gavage, and the poisoning symptom ameliorated at 72h. The changes of BCYP concentration depended on degradation time and tissues. Lizards had a strong capacity to eliminate BCYP with different tissue distribution. The tissues concentration of BCYP from high to low were intestine, stomach, heart, kidney, blood, lung, liver and brain. Bimodal phenomena were observed in lung, liver and kidney. These results may be due to the activities of enzymes, circadian rhythm, and enterohepatic circulation in lizards. Based on the results of organ coefficient and histopathology analysis in liver, the liver was confirmed as the main target organ. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Biliary excretion and enterohepatic recycling of proscillaridin A after oral administration to man

    International Nuclear Information System (INIS)

    Andersson, K.E.; Bergdahl, B.; Wettrell, G.; Linkoeping Univ.

    1977-01-01

    A single oral dose of proscillaridin A (1.0-1.5 mg) was given to six patients with T-tube drainage of the common bile duct, and simultaneous samples of bile and plasma were collected at various times during the following 24 hours. Glycoside activity was assayed by the 86 Rb-uptake inhibition technique. Peak activities in plasma (mean 0.80 ng/ml) were attained after 0.5-2h, and in bile (mean 6.9ng/ml) after 1-4h. Subsequently, proscillaridin activity in bile was less than 5ng/ml for the remainder of the sampling period, and 10-100 times higher than that in plasma. Bile samples treated with β-glucuronidase and sulphatase showed 100-200 fold increase in glycoside activity. Deconjugation was also produced by treatment with enteric contents. The results suggest that conjugation of unchanged proscillaridin is a major metabolic route. After excretion in the bile, the conjugates may be split in the intestine and reabsorbed as active glycoside. (orig.) [de

  19. Oral Administration of α-Asarone Promotes Functional Recovery in Rats With Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Min-Jae Jo

    2018-05-01

    Full Text Available α-asarone, a bioactive compound found in Acorus plant species, has been shown to exhibit neuroprotective, anti-oxidative, anti-inflammatory, and cognitive-enhancing effects. However, the effects of α-asarone on spinal cord injury (SCI have not yet been elucidated. The present study investigated the effects of α-asarone on the mRNA of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis in rats with compressive SCI. α-Asarone was orally administered (10 mg/kg once per day for 14 days following moderate static compression SCI. Compared to controls, α-asarone treatment significantly improved locomotor score, prevented neuroinflammation, and facilitated angiogenesis in the spinal cord at 14 days after SCI. Furthermore, α-asarone significantly reduced the TNF-α, IL-1β, IL-6, monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein 2 (MIP-2, and inducible nitric oxide synthase (iNOS levels but increased the IL-4, IL-10, and arginase 1 levels at 24 h after SCI. At 7 and 14 days after SCI, immunohistochemistry showed reduced reactive gliosis and neuroinflammation and an increased expression of M2 macrophage markers and angiogenesis. The results suggest that the inhibition of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis by α-asarone may be some of the mechanisms underlying the α-asarone-mediated neuroprotective effects on an injured spinal cord.

  20. The dipeptide monoester prodrugs of floxuridine and gemcitabine-feasibility of orally administrable nucleoside analogs.

    Science.gov (United States)

    Tsume, Yasuhiro; Borras Bermejo, Blanca; Amidon, Gordon L

    2014-01-27

    Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5¢-L-phenylalanyl-l-tyrosyl-floxuridine and 5¢-L-phenylalanyl-L-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents.

  1. The Dipeptide Monoester Prodrugs of Floxuridine and Gemcitabine—Feasibility of Orally Administrable Nucleoside Analogs

    Science.gov (United States)

    Tsume, Yasuhiro; Bermejo, Blanca Borras; Amidon, Gordon L.

    2014-01-01

    Dipeptide monoester prodrugs of floxuridine and gemcitabine were synthesized. Their chemical stability in buffers, enzymatic stability in cell homogenates, permeability in mouse intestinal membrane along with drug concentration in mouse plasma, and anti-proliferative activity in cancer cells were determined and compared to their parent drugs. Floxuridine prodrug was more enzymatically stable than floxuridine and the degradation from prodrug to parent drug works as the rate-limiting step. On the other hand, gemcitabine prodrug was less enzymatically stable than gemcitabine. Those dipeptide monoester prodrugs exhibited 2.4- to 48.7-fold higher uptake than their parent drugs in Caco-2, Panc-1, and AsPC-1 cells. Floxuridine and gemcitabine prodrugs showed superior permeability in mouse jejunum to their parent drugs and exhibited the higher drug concentration in plasma after in situ mouse perfusion. Cell proliferation assays in ductal pancreatic cancer cells, AsPC-1 and Panc-1, indicated that dipeptide prodrugs of floxuridine and gemcitabine were more potent than their parent drugs. The enhanced potency of nucleoside analogs was attributed to their improved membrane permeability. The prodrug forms of 5′-l-phenylalanyl-l-tyrosyl-floxuridine and 5′-l-phenylalanyl-l-tyrosyl-gemcitabine appeared in mouse plasma after the permeation of intestinal membrane and the first-pass effect, suggesting their potential for the development of oral dosage form for anti-cancer agents. PMID:24473270

  2. Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

    Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. I-131 attraction by thyroid during first hours following its oral administration

    International Nuclear Information System (INIS)

    Franquiz, J.M.; Cardenas, R.; Blanco, J.; Garcia, M.

    1982-01-01

    From radioisotopic investigations used to study thyroid function, that of I-131 attraction results to be one of the most known and used in medical practice. In the authors' laboratory measurement of I-131 activity upon the gland has been for long adopted at 24 hours after administration; however, current needs compel to look for an early time (within the first six hours) for measuring it. In the paper results of I-131 attraction by thyroid in a group with more than 200 patients at 2,4 and 24 hours following its administration are presented in order to assess a 24 hours attraction representativeness by an early attraction. Results demonstrate early attraction is representative of an attraction at 24 hours and with the same diagnostic usefulness. Normal and doubtful ranks for attraction in our medium are determined at 2 and 6 hours, being adopted as proceeding for those cases whose value should be found within doubtful rank, a measurement at 24 hours in order to determine functional condition of the gland. (author)

  4. Oral administration of a medium containing both D-aspartate-producing live bacteria and D-aspartate reduces rectal temperature in chicks.

    Science.gov (United States)

    Do, P H; Tran, P V; Bahry, M A; Yang, H; Han, G; Tsuchiya, A; Asami, Y; Furuse, M; Chowdhury, V S

    2017-10-01

    1. The aim of this study was to investigate the effects on the rectal temperature of young chicks of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chicks were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chicks were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature. In Experiment 3, after 1 week of chronic oral administration of the medium, 14-d-old chicks were exposed to either high ambient temperature (HT; 40 ± 1°C, 3 h) or control thermoneutral temperature (CT; 30 ± 1°C, 3 h) to monitor the changes in rectal temperature. 3. Chronic, but not acute, oral administration of the medium significantly reduced rectal temperature in chicks, and a chronic effect also appeared under HT conditions. 4. Chronic oral administration of the medium significantly reduced the mRNA abundance of the avian uncoupling protein (avUCP) in the breast muscle, but led to a significant increase in avian adenine nucleotide translocator (avANT) mRNA in the same muscle. 5. (a) These results indicate that the medium can reduce body temperature through the decline in avUCP mRNA expression in the breast muscle that may be involved in reduced mitochondrial proton leaks and heat production. (b) The increase in avANT further suggests a possible enhancement of adenosine triphosphate (ATP) synthesis.

  5. Distribution and binding of [14C]acrylamide to macromolecules in SENCAR and BALB/c mice following oral and topical administration

    International Nuclear Information System (INIS)

    Carlson, G.P.; Weaver, P.M.

    1985-01-01

    To determine if differences in acrylamide distribution or its binding to DNA could be responsible for the reported higher incidence of skin papillomas observed after oral administration compared to topical application, [ 14 C]acrylamide was administered by topical application and oral intubation to male SENCAR and BALB/mice. Portions of lung, liver, stomach, testes, and skin were removed, and 14 C was measured at 15 min, 30 min, 1, 6, 12, 24, and 48 hr. Binding to DNA, RNA, and protein was measured at 6 and 48 hr. Following oral administration, few strain differences in distribution or binding were noted. After topical application, SENCAR mice generally showed higher tissue concentrations than did the BALB/c mice at the early time periods but not at the later ones. Comparing the two routes, comparable concentrations were observed in all tissues except the skin where the amount of [ 14 C]acrylamide after topical application was approximately 100 times that observed after oral administration. At 48 hr, binding to DNA was sevenfold higher after topical than after oral administration. The effect of route on papilloma formation cannot be explained, therefore, on the basis of either a difference in distribution or binding to DNA in the target organ. The binding of acrylamide to DNA in skin was similar in both SENCAR and BALB/c mice indicating that the much greater susceptibility of the SENCAR mice to tumorigenesis cannot be explained simply on the basis of distribution or macromolecular binding

  6. [Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

    Science.gov (United States)

    Wen, Bin-Yu; Li, Jian-Rong

    2013-06-01

    8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

  7. Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin Inflammation in Mice.

    Science.gov (United States)

    Cheng, Hui-Man; Chen, Feng-Yuan; Li, Chia-Cheng; Lo, Hsin-Yi; Liao, Yi-Fang; Ho, Tin-Yun; Hsiang, Chien-Yun

    2017-11-29

    Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner. The thickness and number of cell layers of epidermis were reduced by 29 ± 14.4 and 27.8 ± 11%, respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the biological pathways involved in the immune system and metabolism were significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A, and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 ± 0.08, -2.06 ± 0.21, and -1.62 ± 0.21, respectively. Moreover, vanillin significantly decreased both the amounts of IL-17A and IL-23 and the infiltration of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our findings suggested that vanillin was an effective bioactive compound against psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17 expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.

  8. Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

    Science.gov (United States)

    Sun, Wei; Sanapala, Shilpa; Rahav, Hannah; Curtiss, Roy

    2015-11-27

    A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Pharmacokinetics and dosimetry of the antiandrogen vinclozolin after oral administration in the rat.

    Science.gov (United States)

    Sierra-Santoyo, Adolfo; Castañeda-Hernández, Gilberto; Harrison, Randy A; Barton, Hugh A; Hughes, Michael F

    2008-11-01

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and tissues by high performance liquid chromatography/diode array detector/mass spectrometer. V, 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), and five other metabolites were detected in serum and tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean serum concentration data for V were fitted to a one-compartment model for kinetic analysis. At 2 h, V serum concentration peaked; whereas only trace levels were detected at 24 h (t(1/2 elim) = 3.6 h). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 h, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 h. M5 was the main metabolite in serum and tissues. Serum M5 levels were 5-fold higher than V and 2-fold greater than M1 at all times. At 48 h, M5 remained the main metabolite (t(1/2 elim) = 13.1 h). Liver and kidney exhibited the highest levels of M5, V, and M1. M2 and 3,5-dichloroaniline had the lowest levels of V metabolites in serum and tissues. V is well absorbed, extensively metabolized and widely distributed. M5, the most abundant V metabolite, may be used as an exposure biomarker for pharmacokinetic modeling. These results may clarify the relationship between toxicity and tissue dose of V and its metabolites.

  10. Improved Safety, Bioavailability and Pharmacokinetics of Zidovudine through Lactoferrin Nanoparticles during Oral Administration in Rats.

    Directory of Open Access Journals (Sweden)

    Prashant Kumar

    Full Text Available Zidovudine (AZT is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50-75% the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano. The nanoparticles (NPs are of 50-60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery.

  11. Pharmacokinetics of diclofenac potassium after oral administration of sachets and tablets

    Directory of Open Access Journals (Sweden)

    A Martso

    2008-01-01

    Results. There is evidence that patients tolerate both its sachets and tablets equally well, as confirmed by subjective and objective observations. There are neither marked side effects nor considerable changes in laboratory tests and in the values of vital functions. Diclofenac potassium as early-action tablets (50 and 100 mg exerts a very good analgesic effect in treating migraine since the plasma concentration of the drug peaks on an average of an hour of administration (range 0,33-2 hours and the analgesic effect developed following 60-90 min. Conclusion. By comparing the rate of absorption, it may be concluded that diclofenac potassium as sachets will produce a much rapider analgesic effect. Thus, the high solubility of diclofenac potassium and its very good absorbability (as sachets in particular make the drug a superior analgesic that has a rapid analgesic activity.

  12. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    Science.gov (United States)

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

  13. Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia.

    Science.gov (United States)

    Ohara, Kazuyuki; Kiyotani, Yuka; Uchida, Asako; Nagasaka, Reiko; Maehara, Hiroyuki; Kanemoto, Shigeharu; Hori, Masatoshi; Ushio, Hideki

    2011-06-15

    Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress. Copyright © 2011 Elsevier GmbH. All rights reserved.

  14. Antimicrobial peptide CAP18 and its effect on Yersinia ruckeri infections in rainbow trout Oncorhynchus mykiss (Walbaum): comparing administration by injection and oral routes

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar; Mehrdana, F.; Hansen, Egon Bech

    2017-01-01

    The antimicrobial peptide CAP18 has been demonstrated to have a strong in vitro bactericidal effect on Yersinia ruckeri, but its activity in vivo has not been described. In this work, we investigated whether CAP18 protects rainbow trout Oncorhynchus mykiss (Walbaum) against enteric red mouth...... the conventional antibiotic oxolinic acid. Oral administration of CAP18 to trout did not prevent infection. The proteolytic effect of secretions on the peptide CAP18 in the fish gastrointestinal tract is suggested to account for the inferior effect of oral administration....

  15. Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

    2017-07-15

    OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

  16. Protein binding of N-2-mercaptoethyl-1,3-diaminopropane via mixed disulfide formation after oral administration of WR 2721

    Energy Technology Data Exchange (ETDEWEB)

    Tabachnik, N.F.; Blackburn, P.; Peterson, C.M.; Cerami, A.

    1982-02-01

    Earlier studies have shown that WR 2721 (H2N-(CH2)3-NH(CH2)2SPO3H2) is converted to its free thiol form, N-2-mercaptoethyl-1,3-diaminopropane (MDP), at the acidic pH of the stomach. MDP is a radioprotective compound and a mucolytic agent capable of decreasing sputum viscosity in the lungs of patients with cystic fibrosis. Conversion of WR 2721 and MDP to the corresponding sulfonic acid (MDP-SO3H) permits quantitative determination of these compounds in physiological fluids by use of an automatic amino acid analyzer. After oral administration of WR 2721 to human patients and rabbits it is converted to MDP and the free thiol form of the drug associates with plasma proteins by mixed disulfide linkage. The plasma proteins serve as a depot and reservoir of MDP for potential exchange at the tissues. When incubated with whole sputum or with purified mucin solutions in vitro, MDP decreased the viscosity of these solutions by reduction of the accessible disulfide bonds of the mucin molecule and was subsequently found in mixed disulfide association with the mucin molecule. The association of MDP with proteins via mixed disulfide linkage has important implications for the development of optimal dose regimens for administration of WR 2721 to patients.

  17. Protein binding of N-2-mercaptoethyl-1,3-diaminopropane via mixed disulfide formation after oral administration of WR 2721

    International Nuclear Information System (INIS)

    Tabachnik, N.F.; Blackburn, P.; Peterson, C.M.; Cerami, A.

    1982-01-01

    Earlier studies have shown that WR 2721 [H2N-(CH2)3-NH(CH2)2SPO3H2] is converted to its free thiol form, N-2-mercaptoethyl-1,3-diaminopropane (MDP), at the acidic pH of the stomach. MDP is a radioprotective compound and a mucolytic agent capable of decreasing sputum viscosity in the lungs of patients with cystic fibrosis. Conversion of WR 2721 and MDP to the corresponding sulfonic acid (MDP-SO3H) permits quantitative determination of these compounds in physiological fluids by use of an automatic amino acid analyzer. After oral administration of WR 2721 to human patients and rabbits it is converted to MDP and the free thiol form of the drug associates with plasma proteins by mixed disulfide linkage. The plasma proteins serve as a depot and reservoir of MDP for potential exchange at the tissues. When incubated with whole sputum or with purified mucin solutions in vitro, MDP decreased the viscosity of these solutions by reduction of the accessible disulfide bonds of the mucin molecule and was subsequently found in mixed disulfide association with the mucin molecule. The association of MDP with proteins via mixed disulfide linkage has important implications for the development of optimal dose regimens for administration of WR 2721 to patients

  18. Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

    Science.gov (United States)

    Elkind-Hirsch, K E; Anania, C; Malinak, R

    1996-09-01

    To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

  19. Radioimmunoassay of serum d-Norgestrel in women following oral and intravaginal administration

    International Nuclear Information System (INIS)

    Stanczyk, F.Z.; Hiroi, M.; Goebelsmann, U.; Brenner, P.F.; Lumkin, M.E.; Mishell, D.R. Jr.

    1975-01-01

    A radioimmunoassay (RIA) method for measuring d-Norgestrel (d-Ng) in serum has been developed utilizing petroleum ether extraction, an antiserum raised against d-Norgestrel-3-(0-carboxymethyl) oxime-epsilon-aminocaproic acid--boxine serum albumin, d-Norgestrel-3-(0-carboxymethyl) imino-[ 125 I]-iodohistamine, and dextran-coated charcoal separation. Control serum blanks were undetectable, 6 pg of d-Ng was measurable in 0.1 ml of serum with a high reliability, and intra- and interassay coefficients of variation were 4.4 and 4.9 percent, respectively. d-Ng added to control serum was quantitatively recovered. This RIA proved to be highly specific for d-Ng, cross-reacting less than 0.01 percent with 1-Ng and some 4 to 8 percent with 5α- and 5β-tetrahydro-d-Ng. Serum d-Ng levels measured in 3 women after ingestion of 75 μg of dl-Ng rose to 1.5 to 2 ng/ml within 1/2 to 2-3 hours after oral intake and fell rapidly thereafter to 0.2 to 0.4 ng/ml within 24 hours. Insertion of Silastic intravaginal rings (IVRs), containing 50 or 100 mg of dl-Ng, into 3 women for periods of 3 weeks resulted in a rapid rise of serum d-Ng after insertion. Serum d-Ng levels were highest 24 to 48 hours after the first insertion of each IVR, reaching peak levels of about 5 and 7 to 11 ng/ml, respectively, and declined gradually during the ensuing 15 to 20 days to some 30 to 40 percent of the peak serum d-Ng concentration. Serum d-Ng levels attained after IVR reinsertion remained relatively constant at 1 to 3 ng/ml during each subsequent cycle in all subjects and fell rapidly after each IVR removal. Serum estradiol and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited

  20. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

    Science.gov (United States)

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Symbiotic maple saps minimize disruption of the mice intestinal microbiota after oral antibiotic administration.

    Science.gov (United States)

    Hammami, Riadh; Ben Abdallah, Nour; Barbeau, Julie; Fliss, Ismail

    2015-01-01

    This study was undertaken to evaluate the in vivo impact of new symbiotic products based on liquid maple sap or its concentrate. Sap and concentrate, with or without inulin (2%), were inoculated with Bifidobacterium lactis Bb12 and Lactobacillus rhamnosus GG valio at initial counts of 2-4 × 10(8) cfu mL(-1). The experiments started with intra-gastric administration of antibiotic (kanamycin 40 mg in 0.1 cc) (to induce microbiota disturbance and/or diarrhea) to 3-to-5-week-old C57BL/6 female mice followed by a combination of prebiotic and probiotics included in the maple sap or its concentrate for a week. The combination inulin and probiotics in maple sap and concentrate appeared to minimize the antibiotic-induced breakdown of mice microbiota with a marked effect on bifidobacterium and bacteroides levels, thus permitting a more rapid re-establishment of the baseline microbiota levels. Results suggest that maple sap and its concentrate represent good candidates for the production of non-dairy functional foods.

  2. Serum calcium response following oral zinc oxide administrations in dairy cows

    DEFF Research Database (Denmark)

    Thilsing-Hansen, T; Jørgensen, R J; Thilsing, Trine

    2001-01-01

    Six non-pregnant cows were allocated into 3 groups. Group 1 comprised a pair of lactating cows, whereas groups 2 and 3 each comprised a pair of non-lactating cows. The cows in groups 1 and 2 were dosed intraruminally by stomach tube with zinc oxide at 120 mg Zn per kg of bodyweight at weekly...... intervals for a period of 33 days. Each cow received a total of 4 doses of zinc oxide. Group 3 served as non-treated control group. Blood samples were collected from all 6 cows daily. Serum was analysed for concentration of calcium. Within 12-24 h of each zinc oxide administration the serum calcium...... of the hypocalcaemic response decreased with the number of zinc oxide dosings. This effect was explained as a response from the stimulation of the calcium homeostatic mechanisms. In the Zn dosed non-lactating cows responses were similar but less clear. The perspective of these findings is discussed in relation...

  3. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  4. [Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats].

    Science.gov (United States)

    Mazurek-Mochol, Małgorzata

    2002-01-01

    Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine

  5. Online video in clinical skills education of oral medication administration for undergraduate student nurses: a mixed methods, prospective cohort study.

    Science.gov (United States)

    Holland, Agi; Smith, Fiona; McCrossan, Gill; Adamson, Elizabeth; Watt, Susan; Penny, Kay

    2013-06-01

    Improvements in the safety of the prescribing, dispensing and administration of medicines are identified as a priority across international healthcare systems. It is therefore essential that higher education institutions play their part in helping to meet this patient safety objective. New developments in clinical skills education which are aligned to emerging educational theory are available, but evaluations and supportive evidence are limited. To evaluate the use of an online best practice exemplar as an adjunct to the clinical skills teaching of oral medication administration to undergraduate student nurses. Mixed-methods prospective cohort design. Two intakes of undergraduate nursing students (n=168, n=154) undertaking a first year clinical skills based module at a British university. The Control group received standard teaching using lectures and skills classes facilitated by experienced clinical skills lecturers. The Intervention group received the standard teaching and unlimited access to an online video clip of medication administration. Performance and satisfaction were measured using module assessment results and a satisfaction questionnaire. Qualitative data were gathered using focus groups (n=16, n=20). The Intervention group was significantly (p=0.021) more likely to pass the assessment and rate their satisfaction with the teaching significantly higher (pTeaching and Time and when Classroom Learning was positive, the Transfer to Practice of the clinical skill was enhanced. An online video of a best practice exemplar as an adjunct to taught clinical skills sessions improves student assessment results and satisfaction ratings. The video was also reported to positively influence all themes identified in Classroom Learning and was perceived to promote the Transfer to Practice of teaching input. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

    Science.gov (United States)

    Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

    2017-02-01

    This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl 2 ). After 15 days of oral administration of CO (2 ml kg -1 body weight) and MO (2 ml kg -1 body weight) along with intraperitoneal (i.p.) administration of HgCl 2 (5 mg kg -1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl 2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl 2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl 2 (2 ml kg -1 body weight + 5 mg kg -1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl 2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl 2 -induced oxidative damage. © 2016 Blackwell Verlag GmbH.

  7. Simultaneous oral administration of Salmonella Infantis and S. Typhimurium in chicks.

    Science.gov (United States)

    Murakami, Koichi; Maeda-Mitani, Eriko; Onozuka, Daisuke; Noda, Tamie; Sera, Nobuyuki; Kimura, Hirokazu; Fujimoto, Shuji; Murakami, Satoshi

    2017-01-01

    To confirm the hypothesis that Salmonella enterica subspecies enterica serovar ( S. ) Infantis has higher basic reproductive rates in chicks compared with other Salmonella serovars, 1-day-old specific-pathogen-free chicks ( n  = 8) were challenged simultaneously with S. Infantis and S. Typhimurium per os . Challenged chicks (Group A) were then housed with non-infected chicks (Group B, n  = 4) for 6 days (from 2 to 8 days of age). Group B birds were then housed with other non-infected birds (Group C, n  = 4), which were then transferred to cages containing a further group of untreated chicks (Group D, n  = 2). A control group consisting of four non-infected chicks was used for comparison. All chickens were humanely sacrificed at 18 days of age, and Salmonella from bowel and liver samples were enumerated. Both serovars were isolated from all groups except the control group. S. Typhimurium was isolated at a greater frequency than S. Infantis from the bowel samples of chicks from Groups B, C and D, while no differences in colonisation rates were observed between the two serovars in liver samples from Groups B, C and D. S. Typhimurium, but not S. Infantis, was immunohistochemically detected in the lamina propria of the cecum and rectum in five birds of Group A. Despite the competitive administration, neither of the two serovars completely excluded the other, and no differences were observed in basic reproductive rates between the two serovars. These findings, together with data from previous studies, suggest that the initial quantitative domination of S. Infantis in chicken flocks may explain why this serovar is predominant in broiler chickens.

  8. Evaluation of a novel dry eye model induced by oral administration of finasteride.

    Science.gov (United States)

    Li, Kai; Zhang, Chuanwei; Yang, Zichao; Wang, Yuliang; Si, Haipeng

    2017-12-01

    Dry eye is a common eye disease, and suitable animal models are indispensable for investigating the pathogenesis and developing treatments for dry eye. The present study was conducted to develop an androgen deficiency dry eye model induced by finasteride, and to evaluate ocular surface status and inflammatory cytokine gene expression in the lacrimal gland using a cytokine antibody array system. The results revealed that the antiandrogenic drug finasteride induced significant tear deficiency, and the histopathology results revealed significant inflammatory cell infiltration in the lacrimal gland. The cytokine antibody array system identified increased B7‑2 (also known as cluster of differentiation 86), interleukin (IL)‑1β, IL‑4, IL‑6, IL‑10, matrix metalloproteinase‑8, Fas ligand, tumor necrosis factor (TNF)‑α and metalloproteinase inhibitor 1 levels in the lacrimal gland of the dry eye model. These cytokines were validated as candidate markers through the use of western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Both analyses confirmed a significant increase in proinflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and anti‑inflammatory cytokines, including IL‑4 and IL‑10. The aforementioned data suggested that inflammation in antiandrogenic models resulted from a balance between inflammatory and anti‑inflammatory responses. Thus, direct finasteride administration may produce an applicable model for dry eye mediated by androgen deficiency. In addition, there may be a correlation between sex, steroid deficiency and the inflammatory response. The findings of the present study have provided useful information for the pathogenesis and diagnosis of dry eye mediated by androgen deficiency.

  9. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Sheela Devi, Rathinasamy

    2015-03-01

    Aspartame is a non-nutritive sweetener particularly used in 'diet' and 'low calorie' products and also in a variety of foods, drugs and hygiene products. Aspartame is metabolized by gut esterases and peptidases to three common chemicals: the amino acids, aspartic acid and phenylalanine, and small amounts of methanol. The aim of the present study was to assess potential changes in molecular mediators of aspartame as a chemical stressor in rats. The effects of long-term administration of aspartame (40 mg/kg body weight/day) were tested in Wistar Albino rats. The treatment effects were assessed in different conditions, including control groups. After 90 days of treatment, circulating concentrations of different parameters were assessed: corticosterone, lipid peroxidation, antioxidant activity, nitric oxide, reduced glutathione and cytokines (interleukin 2, interleukin 4, tumor necrosis factor-α and interferon-γ). The results show that there was a significant increase in plasma corticosterone, serum lipid peroxidation and nitric oxide level along with a decrease in enzymatic and non-enzymatic antioxidant as well as significant decrease in interleukin 2, tumor necrosis factor-α and interferon-γ. There was also a significant increase in interleukin 4 irrespective of whether the animals were immunized or not. The findings clearly point out that aspartame acts as a chemical stressor because of increased corticosterone level and increased lipid peroxidation and nitric oxide level induce generation of free radicals in serum which may be the reason for variation of cytokine level and finally results in alteration of immune function. Aspartame metabolite methanol or formaldehyde may be the causative factors behind the changes observed. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  10. Identification of the Chemical Constituents in Simiao Wan and Rat Plasma after Oral Administration by GC-MS and LC-MS

    Directory of Open Access Journals (Sweden)

    Yunshuang Fan

    2017-01-01

    Full Text Available Simiao Wan (SMW, an important multiherbal formula used in traditional Chinese medicine, is extensively used to treat rheumatoid arthritis. However, the knowledge of the bioactive components of SMW remains unclear. Thus, gas chromatography–mass spectrometry (GC-MS and liquid chromatography–mass spectrometry (LC-MS were used to analyze the chemical constituents of volatile and nonvolatile extracts of SMW, as well as its absorbed components in rat plasma after oral SMW administration. Identification of several compounds was enabled by comparison of retention times, MS spectra, and MS/MS spectral data with the standard substance and reference materials reported in the literature. In the volatile extracts, GC-MS identified 26 compounds in vitro, three of which observed in blood by GC-MS. In the nonvolatile extracts, LC-MS identified 49 compounds in SMW; 18 compounds containing 7 prototype compounds, 5 metabolites, and 6 unknown compounds were absorbed by blood. The proposed GC-MS and LC-MS method was appropriate not only for the rapid screening and identification of multiple components of an SMW extract but also for screening its bioactive constituents in vivo. The proposed method could be a promising tool for the quality control of other Chinese herbal medicines.

  11. Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

    International Nuclear Information System (INIS)

    Conney, Allan H.; Zhou, Sherry; Lee Maojung; Xie Jianguo; Yang, Chung S.; Lou Yourong; Lu Yaoping

    2007-01-01

    Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers. Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans

  12. The Development of Multiple Intelligence Capabilities for Early Childhood Development Center, Local Administration Organization in Chaiyaphum Province

    Science.gov (United States)

    Siphai, Sunan; Supandee, Terdsak; Raksapuk, Chunpit; Poopayang, Piangkhae; Kratoorerk, Sangsan

    2017-01-01

    The aim of this research is to promote multiple intelligence capabilities for Early Childhood Care Center of a Sub-district Administration Organization in Chaiyaphum Province. The sample applied were 61 children aging between 3 and 5 years old at Child Development Center, Tambon Ban Kok, Amphoe Chaturus, Chaiyaphum Province, who were selected…

  13. Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.

    Science.gov (United States)

    Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

    2013-11-01

    Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200 mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75 mg/kg and 150 mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25 ± 0.24 mg/L h to 7.62 ± 0.15 mg/L h and 4.97 ± 0.21 mg/L h, and the C(max) value was decreased from 1.31 ± 0.03 mg/L to 0.62 ± 0.05 mg/L and 0.36 ± 0.04 mg/L in rats pretreated with ursodeoxycholic acid at doses of 75 mg/kg and 150 mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. Georg Thieme Verlag KG Stuttgart · New York.

  14. 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.

  15. COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

    Science.gov (United States)

    COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

  16. Effect of oral administration of probiotics on growth performance, apparent nutrient digestibility and stress-related indicators in Holstein calves.

    Science.gov (United States)

    Zhang, R; Zhou, M; Tu, Y; Zhang, N F; Deng, K D; Ma, T; Diao, Q Y

    2016-02-01

    This study aimed to investigate the effect of dietary supplementation with Lactobacillus plantarum and Bacillus subtilis on growth performance, apparent nutrient digestibility and stress-related indicators in dairy calves. Twenty-four neonatal Holstein calves were randomly allocated to three treatments: a basal diet with no supplementation (control), the basal diet supplemented with 1.7 × 10(10) CFU per head per day (CFU/h.d) of L. plantarum GF103 (LB group) or the basal diet supplemented with a mixture of L. plantarum GF103 (1.7 × 10(10) CFU/h.d) and B. subtilis B27 (1.7 × 10(8) CFU/h.d) (LBS group). Dry matter intake (DMI), average daily gain (ADG), feed conversation ratio (FCR), apparent digestibility of nutrients and stress-related indicators were measured in this trail. The result indicated that no significant differences were observed in DMI or ADG (p > 0.05), but the FCR was improved in the LB group over the first 12 weeks (p > 0.05). The apparent digestibility of nutrients was not altered by probiotics in week 6 (p > 0.05), but the apparent digestibility of total phosphorus was significantly greater in the LB and LBS groups in week 8 (p > 0.05); additionally, an increase in the apparent digestibility of crude protein was detected in the LBS group (p > 0.05). Oral administration of L. plantarum alone improved the T-lymphocyte transformation rate on days 58 and 62 (p > 0.05), while adding the mixture of L. plantarum and B. subtilis increased the T-lymphocyte transformation rate (p > 0.05) but decreased the content of cortisol on day 58 (p > 0.05). No significant differences were detected between the LB and LBS groups in growth performance, apparent digestibility of nutrients and stress-related indicators (p > 0.05). The results suggested that oral administration of L. plantarum improved growth performance, nutrient digestibility and relieved weaning stress in calves, but no additional effect was obtained by supplementation with B. subtilis. Journal of

  17. Comparison between the Effects of Oral and Intramuscular Administration of Shin’iseihaito (Xinyiqingfeitang in a Streptococcus pyogenes-Induced Murine Sinusitis Model

    Directory of Open Access Journals (Sweden)

    Masaaki Minami

    2018-01-01

    Full Text Available Streptococcus pyogenes (S. pyogenes is a species of Gram-positive coccoid bacteria having many virulence factors. Its capsule and exotoxins can cause upper respiratory tract infections such as sinusitis. The general treatment for S. pyogenes-induced sinusitis is administration of antibiotics such as penicillin and macrolides; however, a serious problem associated with these antibiotics is their attenuated effect. Shin’iseihaito (Xinyiqingfeitang, a formula of Japanese traditional Kampo medicine and traditional Chinese medicine, has been used for the treatment of sinusitis. In general, formulas of Japanese traditional Kampo medicine are orally administered. This is in contrast to certain formulas of traditional Chinese medicine, which are being recently administered intramuscularly or intravenously. Regarding these traditional Chinese medicine formulas, the injection methodology is reported to be more effective than oral intake. In this study, we compared the efficacy between orally and intramuscularly administered Shin’iseihaito against S. pyogenes-induced sinusitis. We evaluated the antibacterial effect of Shin’iseihaito extract (SSHT against S. pyogenes by K-B disk diffusion assay. Furthermore, we investigated the nasal colonization of S. pyogenes, determined cytokine (TNF-α, IL-1β, and IL-6 levels, and conducted a splenocyte proliferative assay in a murine sinusitis model. SSHT displayed direct anti-S. pyogenes activity. Intramuscular administration of SSHT decreased the nasal colonization of S. pyogenes compared with oral administration. Thymidine uptake analysis revealed that the proliferation of splenocytes from S. pyogenes-infected mice under intramuscular SSHT treatment was upregulated compared to that of splenocytes from S. pyogenes-infected mice under oral SSHT treatment. We also found that TNF-α, IL-1β, and IL-6 levels in the nasal discharge from intramuscularly treated S. pyogenes-infected mice were lower than those from

  18. SURVEY OF SHORT-TERM ORAL CORTICOSTEROID ADMINISTRATION BY ORTHOPAEDIC PHYSICIANS IN COLLEGE AND HIGH SCHOOL ATHLETES

    Directory of Open Access Journals (Sweden)

    Albert W. Pearsall IV

    2009-03-01

    Full Text Available The use of oral corticosteroid (OCS drugs is advocated because of their potent anti-inflammatory effects. They also possess many potential adverse effects. No study has assessed physician prescribing practices of OCS therapy in high school (HS or college (COL athletes. This paper reports the prescribing patterns of sports medicine physicians who used short-term OCS therapy and to describe associated complications in HS and COL athletes within a 24- month period. An internet link to a descriptive epidemiology survey was included in an e-mail to all members of the Arthroscopy Association of North America and the American Orthopaedic Society for Sports Medicine. Descriptive statistics and correlation analysis were used to examine responses. Total response rate was 32% (615/1,928. Sixty-six percent of the physicians indicated prescribing OCS to both groups of athletes, while 29% reported prescribing OCS to COL athletes and 5% to HS athletes for musculoskeletal injuries. Physicians who prescribed multiple OCS regimens to the same athlete within the same season (P = 0.01 and physicians who prescribed OCS to the skeletally immature athlete (P = 0.009 reported more complications than other physicians. Among the 412 physicians who did not prescribe OCS in the treatment of athletic induced musculoskeletal injury, 251 (61% cited a risk of developing medical complications as the primary reason for avoiding use. The reported number of medical complications was low with no cases of avascular necrosis reported for the 2-year recall period. Orthopaedic surgeons who treated athletic induced musculoskeletal injuries with a short-term course of oral corticosteroids reported that high school and college athletes benefited with few medical complications

  19. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  20. Cocaine Self-Administration Alters the Relative Effectiveness of Multiple Memory Systems during Extinction

    Science.gov (United States)

    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.

    2009-01-01

    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable "habit" and "cognitive" memory systems, respectively. In the response extinction condition, rats performed a runway approach response…

  1. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

  2. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Science.gov (United States)

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  3. The impact of vehicles on the mucoadhesive properties of orally administrated nanoparticles: a case study with chitosan-4-thiobutylamidine conjugate.

    Science.gov (United States)

    Sakloetsakun, Duangkamon; Perera, Glen; Hombach, Juliane; Millotti, Gioconda; Bernkop-Schnürch, Andreas

    2010-09-01

    The aim of this study was to evaluate the impact of various vehicles on mucoadhesive properties of thiolated chitosan nanoparticles both in vitro and in vivo. Nanoparticles (NPs) were prepared by in situ gelation technique followed by labeling with fluorescein diacetate. Comparative studies on mucoadhesion were done with these thiolated chitosan NPs and unmodified chitosan NPs (control). The obtained nanoparticles displayed a mean diameter of 164.2 ± 6.9 nm and a zeta potential of 21.5 ± 5 mV. In an in vitro adhesion study, unhydrated thiolated NPs adhered strongly to freshly excised porcine small intestine, which was more than threefold increase compared to the control. In contrast, in the presence of various vehicles (PEG 300, miglyol 840, PEG 6000, cremophor EL, and caprylic triglyceride), the mucoadhesive properties of thiolated NPs were comparatively weak. Thiolated NPs suspended in caprylic triglyceride, for example, had a percent mucoadhesion of 22.50 ± 5.35% on the mucosa. Furthermore, results from in vivo mucoadhesion studies revealed that the dry form of nanoparticles exhibits the strongest mucoadhesion, followed by nanoparticles suspended in PEG 300, miglyol, and 100 mM phosphate buffer, in that order. Three hours after administration, the gastrointestinal residence time of the dry form of thiolated NPs was up to 3.6-fold prolonged. These findings should contribute to the design of highly effective oral mucoadhesive nanoparticulate drug delivery systems.

  4. Lecithin-based microemulsion of a peptide for oral administration: preparation, characterization, and physical stability of the formulation.

    Science.gov (United States)

    Cilek, Ayşe; Celebi, Nevin; Tirnaksiz, Figen

    2006-01-01

    The objective of our study was to prepare and characterize a stable microemulsion formulation for oral administration of a peptide, e.g., rh-insulin. The microemulsions were prepared using Labrafil M 1944 CS, Phospholipon 90G (lecithin), absolute alcohol, and bidistilled water. Commercially available soybean lecithins (namely, Phospholipon 80, phosphatidylcholine purity 76 +/- 3%, and Phospholipon 90G, phosphatidylcholine purity 93 +/- 3%) were used in the study. The results showed that the phase diagram obtained using a low purity lecithin was not similar to that obtained with a high purity lecithin. We observed that the microemulsion area was wider at the phase diagram obtained with the higher purity lecithin. We found that the extent of the microemulsion region depended upon both the purity of the lecithin and the surfactant/co-surfactant (s/co-s) mixing ratios (K(m)). The rheological studies showed that microemulsions followed a Newtonian behavior. Such physical characteristics as viscosity, turbidity, density, conductivity, refractive index, droplet size, physical appearance, and phase separation of the microemulsion were measured at different temperatures (4 degrees C, 25 degrees C, and 40 degrees C) during 6 months. The results indicated that the physical characteristics of the developed microemulsions did not change under different storage temperatures (p > 0.05).

  5. Effect of oral administration of Tribulus terrestris extract on semen quality and body fat index of infertile men.

    Science.gov (United States)

    Salgado, R M; Marques-Silva, M H; Gonçalves, E; Mathias, A C; Aguiar, J G; Wolff, P

    2017-06-01

    Male fertility can be evaluated through complete semen analysis. Plants belonging to the Tribulus genus are known for their role in enhancing sex hormone levels and semen quality. The aim of this study was to evaluate the effects of T. terrestris on semen quality and physiological parameters. Sixty-five men with abnormal semen evaluation were included in this study, in which they were prescribed with oral administration of Androsten ® (250 mg of Tribulus terrestris dried extract per capsule). Body fat percentage, lean muscle mass gain, fluctuation in steroid hormone levels and all semen parameters were analysed during the period of treatment. The results demonstrated that decrease in the percentage of body fat and increase in lean mass were significant, as well as increase in dihydrotestosterone levels. Complete semen analysis evaluated at the end of treatment showed significant enhancement in sperm concentration, motility and liquefaction time. Protodioscin, the main phytochemical agent of the Tribulus genus, acts on sertoli cells, germ cell proliferation and growth of seminiferous tubules. This component is known to convert testosterone into dihydrotestosterone, which plays important roles in male attributes. Our results indicate the therapeutic use of Tribulus terrestris by men presenting altered semen parameters, and/or undergoing infertility treatment. © 2016 Blackwell Verlag GmbH.

  6. The effect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice.

    Science.gov (United States)

    Sharma, Veena; Sharma, Arti; Kansal, Leena

    2010-03-01

    Lead is a common environmental occupational toxic metal, known to have indirect oxidative effects. Considering the antioxidant properties of garlic, this study was undertaken to evaluate the therapeutic efficacy of garlic extracts in terms of normalization of altered hematological, biochemical and immunological parameters, and depletion of inorganic lead burden in blood, kidney and brain tissues. Chronic lead nitrate ingestion showed a significant decline in total erythrocyte count, total leukocyte count, hemoglobin concentration, lymphocyte and monocyte content, while neutrophil content increased in lead nitrate treated group. Pb(NO(3))(2) exposure elicited a significant escalation in thiobarbituric acid reactive substances level and depletion in reduced glutathione content and antioxidant enzymes namely, superoxide dismutase and catalase in kidney and brain. Activities of aspartate transaminase, alanine transaminase, acid phosphatase and alkaline phosphatase augmented significantly in kidney and brain of lead exposed mice. Lead nitrate treatment decreased protein content while cholesterol and lead burden increased significantly. A decrease in viability of macrophage, phagocytic index, immunoglobulin level and plaque count were the salient features observed in lead exposed animals. However, oral administration of garlic extracts to Pb(NO(3))(2) treated groups attenuated the deranged parameters to some extent. This indicates that garlic can be a protective regimen for lead toxicity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  7. The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal.

    Science.gov (United States)

    Karrasch, Nicole M; Lerche, Phillip; Aarnes, Turi K; Gardner, Heather L; London, Cheryl A

    2015-08-01

    This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.

  8. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice.

    Science.gov (United States)

    Hu, Jingtao; Wang, Chunfeng; Ye, Liping; Yang, Wentao; Huang, Haibin; Meng, Fei; Shi, Shaohua; Ding, Zhuang

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

  9. Determination of rhynchophylline and hirsutine in rat plasma by UPLC-MS/MS after oral administration of Uncaria rhynchophylla extract.

    Science.gov (United States)

    Wu, Yu-Tse; Lin, Lie-Chwen; Tsai, Tung-Hu

    2014-03-01

    An ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to concurrently determine rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma was achieved by alkalization and liquid-liquid extraction. The mass transition of precursor ion → product ion pairs were monitored at m/z 385.2 → 160.0 for rhynchophylline, m/z 369.3 → 144.0 for hirsutine and m/z 414.0 → 220.0 for noscapine (internal standard). This method revealed linear relationships from 2.5 to 50 ng/mL (r(2)  > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r(2)  > 0.998) for hirsutine. The limit of quantification values for rhynchophylline and hirsutine in rat plasma were both 2.5 ng/mL. Intra-day and inter-day precisions were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and the accuracy (bias) was 83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal standard. This method was applied successfully to a pharmacokinetic study of rhynchophylline and hirsutine in rats after oral administration. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

    Directory of Open Access Journals (Sweden)

    Anat Frydman-Marom

    Full Text Available An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ play a key role in Alzheimer's disease (AD pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt, which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

  11. Oral administration of curcumin (Curcuma longa) can attenuate the neutrophil inflammatory response in zymosan-induced arthritis in rats.

    Science.gov (United States)

    Nonose, Nilson; Pereira, José Aires; Machado, Paulo Roberto Moura; Rodrigues, Murilo Rocha; Sato, Daniela Tiemi; Martinez, Carlos Augusto Real

    2014-11-01

    To evaluate the effect of curcumin in the acute phase of zymosan-induced arthritis. Twenty-eight male rats were subjected to intra-articular infiltration of zymosan of both knees and, in four the infiltration was made with saline. The animals were divided into five groups second received every six hours by gavage: corn oil by (positive and negative control); curcumin (100 mg/kg); prednisone 1 mg/kg/day; prednisone 8 mg/kg. All animals were sacrificed after six, 12, 24 and 48 hours of the infiltration. The knees were removed for evaluation of neutrophil infiltration. The number of neutrophils was counted by computer-assisted analysis of the images. The neutrophil infiltrate was stratified into four grades: 0 = normal; + = mild; ++/+++ = moderate; > ++++ = severe. The results were compared using the Mann-Whitney test and the variance by Kruskal-Wallis test adopting a significance level of 5% (pCurcumin reduces inflammatory activity in the first six hours after zymosan-induced arthritis when compared to saline (pCurcumin was more effective than lower doses of prednisone in the first six hours after induction of the arthritis. After 12, 24 and 48 hours, curcumin does not have the same anti-inflammatory effects when compared to prednisone. After 48 hours, prednisone is more effective than curcumin in reducing the inflammatory infiltrate regardless of the dose of prednisone used. Oral administration of curcumin reduces inflammation in the first six hours after experimentally zymosan-induced arthritis.

  12. Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

    1997-01-01

    The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

  13. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    Science.gov (United States)

    Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0–∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

  14. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    Directory of Open Access Journals (Sweden)

    Zhaohui Ge

    2014-01-01

    Full Text Available Pharmacokinetic characters of rhynchophylline (RIN, gastrodin (GAS, and gastrodigenin (p-hydroxybenzyl alcohol, HBA were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT and gouteng (rhynchophylla alkaloids, EPG. At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and Cmax⁡ and AUC0–∞ (P<0.05 were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint.

  15. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

    2011-01-01

    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  16. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  17. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci.

    Science.gov (United States)

    Pavlova, Sylvia I; Jin, Ling; Gasparovich, Stephen R; Tao, Lin

    2013-07-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci.

  18. Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates

    DEFF Research Database (Denmark)

    Hawley, Samuel; Javaid, M Kassim; Rubin, Katrine H

    2016-01-01

    , Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001 respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p-exit 0.10) and accounting for the competing risk of therapy cessation were used to identify...

  19. Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections

    Directory of Open Access Journals (Sweden)

    Larissa B. Thackray

    2018-03-01

    Full Text Available Summary: Although the outcome of flavivirus infection can vary from asymptomatic to lethal, environmental factors modulating disease severity are poorly defined. Here, we observed increased susceptibility of mice to severe West Nile (WNV, Dengue, and Zika virus infections after treatment with oral antibiotics (Abx that depleted the gut microbiota. Abx treatment impaired the development of optimal T cell responses, with decreased levels of WNV-specific CD8+ T cells associated with increased infection and immunopathology. Abx treatments that resulted in enhanced WNV susceptibility generated changes in the overall structure of the gut bacterial community and in the abundance of specific bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient to alter host immunity and WNV outcome. Our results identify oral Abx therapy as a potential environmental determinant of systemic viral disease, and they raise the possibility that perturbation of the gut microbiota may have deleterious consequences for subsequent flavivirus infections. : Thackray et al. observed increased susceptibility to West Nile, Zika, and Dengue virus infections following oral antibiotic treatment in mice. Antibiotics altered the bacterial abundance and community structure and the development of optimal T cell immunity. These data suggest that antibiotics may have deleterious consequences for subsequent flavivirus infections. Keywords: West Nile virus, Dengue virus, Zika virus, flavivirus, oral antibiotics, gut microbiota, risk factors, pathogenesis determinants, immunity

  20. Multiple recurrent and de novo odontogenic keratocysts associated with oral-facial-digital syndrome

    NARCIS (Netherlands)

    Lindeboom, Jerome A. H.; Kroon, Frans H. M.; de Vires, Jan; van den Akker, Hans P.

    2003-01-01

    In 1954, Papillon-Leage and Psaume were the first to describe the clinical characteristics of oral-facial-digital syndrome (OFDS). On the basis of their clinical features and the inheritance pattern, 2 variants were initially distinguished, namely OFDS type I (Papillon-Leage and Psaume) and OFDS

  1. [Improving the teaching quality by multiple tools and technology in oral histopathology experimental course].

    Science.gov (United States)

    Tian, Zhen; Wang, Li-Zhen; Hu, Yu-Hua; Zhang, Chun-Ye; Li, Jiang

    2017-04-01

    Oral histopathology is a course which needs to be combined with theory and practice closely. Experimental course plays an important role in teaching oral histopathology. Here, we aim to explore a series of effective measures to improve the teaching quality of experimental course and tried to train observation, thinking, analysis and problem solving skills of dental students. We re-edited and updated the experimental textbook "guidelines of experimental course of oral histopathology", and published the reference book for experimental course--"color pocket atlas of oral histopathology: experiment and diadactic teaching". The number of clinicopathological cases for presentation and class discussion was increased, and high-quality teaching slides were added and replaced the poor-quality or worn out slides. We established a variety of teaching methods based on the internet, which provided an environment of self-directed learning for dental students. Instead of simple slice-reading examination, a new evaluation system based on computer was established. The questionnaire survey showed that the students spoke positively on the teaching reform for experimental course. They thought that the reform played a significant role in enriching the teaching content, motivating learning interest and promoting self-study. Compared with traditional examination, computer-based examination showed a great advantage on mastering professional knowledge systematically and comprehensively. The measures adopted in our teaching reform not only effectively improve the teaching quality of experimental course of oral histopathology, but also help the students to have a clear, logical thinking when facing complicated diseases and have the ability to apply theoretical knowledge into clinical practice.

  2. [Functional respiratory and blood gas analytical studies of the effects of fenspiride, in oral and intramuscular administration, in chronic bronchopneumopathic subjects].

    Science.gov (United States)

    Cascella, D; Raffi, G B; Caudarella, R; Gennari, P; Caprara, C; Cipolla, C

    1979-12-01

    A group of 20 chronic bronchopneumopathics was treated for 15 days with fenspiride orally and i.m. The behaviour of a set of functional respiratory and haemogasanalytic parameters was monitored at various times (basic, 5th, 10th and 15th days). Progressive, significant improvements in VC, FEV1, RV and in related parameters were observed. These were attributed to the drug's anti-inflammatory effect in the respiratory ways as well as to its direct antibronchospastic action. Stress is laid on the excellent clinical tolerance of fenspiride following its oral and i.m. administration.

  3. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

  4. Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

    Science.gov (United States)

    Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

    2015-06-01

    To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

  5. Plasticity of the Pyruvate Node Modulates Hydrogen Peroxide Production and Acid Tolerance in Multiple Oral Streptococci.

    Science.gov (United States)

    Cheng, Xingqun; Redanz, Sylvio; Cullin, Nyssa; Zhou, Xuedong; Xu, Xin; Joshi, Vrushali; Koley, Dipankar; Merritt, Justin; Kreth, Jens

    2018-01-15

    Commensal Streptococcus sanguinis and Streptococcus gordonii are pioneer oral biofilm colonizers. Characteristic for both is the SpxB-dependent production of H 2 O 2 , which is crucial for inhibiting competing biofilm members, especially the cariogenic species Streptococcus mutans H 2 O 2 production is strongly affected by environmental conditions, but few mechanisms are known. Dental plaque pH is one of the key parameters dictating dental plaque ecology and ultimately oral health status. Therefore, the objective of the current study was to characterize the effects of environmental pH on H 2 O 2 production by S. sanguinis and S. gordonii S. sanguinis H 2 O 2 production was not found to be affected by moderate changes in environmental pH, whereas S. gordonii H 2 O 2 production declined markedly in response to lower pH. Further investigation into the pyruvate node, the central metabolic switch modulating H 2 O 2 or lactic acid production, revealed increased lactic acid levels for S. gordonii at pH 6. The bias for lactic acid production at pH 6 resulted in concomitant improvement in the survival of S. gordonii at low pH and seems to constitute part of the acid tolerance response of S. gordonii Differential responses to pH similarly affect other oral streptococcal species, suggesting that the observed results are part of a larger phenomenon linking environmental pH, central metabolism, and the capacity to produce antagonistic amounts of H 2 O 2 IMPORTANCE Oral biofilms are subject to frequent and dramatic changes in pH. S. sanguinis and S. gordonii can compete with caries- and periodontitis-associated pathogens by generating H 2 O 2 Therefore, it is crucial to understand how S. sanguinis and S. gordonii adapt to low pH and maintain their competitiveness under acid stress. The present study provides evidence that certain oral bacteria respond to environmental pH changes by tuning their metabolic output in favor of lactic acid production, to increase their acid survival

  6. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    Science.gov (United States)

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  7. Profiling of the compounds absorbed in human plasma and urine after oral administration of a traditional Japanese (kampo) medicine, daikenchuto.

    Science.gov (United States)

    Iwabu, Jun; Watanabe, Junko; Hirakura, Kazuhiro; Ozaki, Yoshinori; Hanazaki, Kazuhiro

    2010-11-01

    Daikenchuto (DKT), a pharmaceutical-grade traditional Japanese (Kampo) medicine, has been widely used for the treatment of various gastrointestinal disorders including postoperative ileus and has been integrated into the modern medical care system in Japan as a prescription drug. DKT is a multiherbal medicine consisting of Japanese pepper (zanthoxylum fruit), processed ginger, and ginseng with maltose as an additive. Despite substantial research on the pharmacological activities of DKT and its ingredients, the lack of studies on absorption, distribution, metabolism, and excretion of DKT has made it difficult to obtain a consistent picture of its mechanism of action. In the present study, we constructed an analysis procedure consisting of seven conditions of liquid chromatography and mass spectrometric analysis, which enabled the identification of 44 ingredients of DKT component herbs. We investigated the plasma and urine profiles of these ingredients 0.5 to 8 h after oral administration of 15.0 g of DKT in four healthy volunteers. The results indicated that 1) hydroxy-α-sanshool and [6]-shogaol, the prominent peaks in plasma derived from Japanese pepper and ginger, respectively, were detected at 0.5 h and thereafter decreased throughout the sampling period; 2) ginsenoside Rb(1), a prominent peak derived from ginseng, increased gradually during the sampling period; 3) glucuronide conjugates of hydroxy-sanshools, shogaols, and gingerols were detected in plasma and urine; and 4) no obvious differences between samples from the two male and the two female individuals were observed. These results provide a strong basis for future studies on pharmacokinetics and pharmacology of DKT.

  8. Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

    Science.gov (United States)

    Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

    2017-12-01

    Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Science.gov (United States)

    Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

    2017-01-01

    Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

  10. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kawahara

    Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

  11. Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year.

    Science.gov (United States)

    Johnson, Kristen M; Zhou, Huanxue; Lin, Feng; Ko, John J; Herrera, Vivian

    2017-08-01

    Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking. To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide. This retrospective study used MarketScan Commercial and Medicare Supplemental claims databases. MS patients with ≥ 1 claim for specified DMTs from April 1, 2013, to June 30, 2013, were identified. The index drug was defined as the first oral DMT within this period. To capture patients newly initiating index DMTs, patients could not have a claim for their index drugs in the previous 12 months. Baseline characteristics were described for patients in each treatment cohort. Adherence, as measured by medication possession ratio (MPR) and proportion of days covered (PDC); persistence (30-day gap allowed); and time to discontinuation over a 12-month follow-up period were compared across treatment cohorts. Adjusted logistic regression models were used to examine adherence, and Cox regression models estimated risk of discontinuation. 1,498 patients newly initiated oral DMTs and met study inclusion criteria: fingolimod (n = 185), dimethyl fumarate (n = 1,160), and teriflunomide (n = 143). Patients were similar across most baseline characteristics, including region, relapse history, and health care resource utilization. Statistically significant differences were observed across the treatment cohorts for age, gender, previous injectable/infused DMT use, and comorbidities. Adherence and time to discontinuation were adjusted for age, gender, region, previous oral

  12. LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma after Oral Administration of Pedunculoside and Ilex rotunda Extract

    Directory of Open Access Journals (Sweden)

    Waiou Zhao

    2015-05-01

    Full Text Available Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM containing 4%–5% pedunculoside (PDC. A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic acid 28-β-D-glucopyranosyl ester (DEOG as an internal standard. The analytes were extracted by protein precipitation and eluted on a C18 chromatography column using a mobile phase of methanol–H2O (70:30, v/v delivered at a flow rate of 0.6 mL/min. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL, with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions (%RSD ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within −7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda extract (IRE. Pharmacokinetic parameters of PDC in IRE, such as Cmax, AUC0–t, AUC0–∞, t1/2z, and CLz/F, statistically differed from those of the pure monomer (p < 0.01. However, Tmax and MRT showed no significant differences between the two groups. Results suggested that other coexisting components in IRE may decrease the absorption of PDC. Compound-compound interactions between PDC and other herbal extract components can alter the pharmacokinetic behavior of PDC. The study will be helpful in providing references for understanding the action mechanism and clinical application of Ilex rotunda.

  13. Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

    Directory of Open Access Journals (Sweden)

    Parayath NN

    2016-08-01

    Full Text Available Neha N Parayath,1 Hayley Nehoff,1 Samuel E Norton,2 Andrew J Highton,2 Sebastien Taurin,1,3 Roslyn A Kemp,2 Khaled Greish1,4 1Department of Pharmacology and Toxicology, 2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 3Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA; 4Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Oral administration of paclitaxel (PTX, a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid (SMA. Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg compared to the commercially available PTX formulation (PTX [Ebewe]. In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe. In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. Keywords: oral delivery, anticancer nanomedicine, CT-26, enhanced permeability and retention (EPR effect, HUVEC, antiangiogenic

  14. Effects of an oral insulin nanoparticle administration on hepatic glucose metabolism assessed by 13C and 2H isotopomer analysis

    NARCIS (Netherlands)

    Reis, C.P.; Neufeld, R.; Veiga, F.; Figueiredo, I.V.; Jones, J.; Soares, A.F.; Nunes, P.M.; Damg\\'e, C.; Carvalho, R.A.

    2012-01-01

    The purpose of this study was to evaluate hepatic glucose metabolism of diabetic induced rats after a daily oral load of insulin nanoparticles over 2 weeks. After the 2-week treatment, an oral glucose tolerance test was performed with [U-��C] glucose and �H2O. Plasma glucose �H and ��C enrichments

  15. LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

    Science.gov (United States)

    Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

    2012-01-01

    This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.

  16. Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents.

    Science.gov (United States)

    Fooks, A R; Jeevarajah, D; Lee, J; Warnes, A; Niewiesk, S; ter Meulen, V; Stephenson, J R; Clegg, J C

    1998-05-01

    The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.

  17. Sensitive UHPLC-MS/MS quantitation and pharmacokinetic comparisons of multiple alkaloids from Fuzi- Beimu and single herb aqueous extracts following oral delivery in rats.

    Science.gov (United States)

    Xu, Yanyan; Li, Yamei; Zhang, Pengjie; Yang, Bin; Wu, Huanyu; Guo, Xuejun; Li, Yubo; Zhang, Yanjun

    2017-07-15

    Aconiti Lateralis Radix Praeparata- Fritillariae Thunbergii bulbus, namely Fuzi- Beimu in Chinese, is a classic herb pair whose combined administration was prohibited according to the rule of "Eighteen antagonisms". However, incompatibility of Fuzi and Beimu has become controversial because of the application supported by many recorded ancient prescriptions and increasing modern researches and clinical practice. The present study aimed to investigate the pharmacokinetic differences of multiple alkaloids from Fuzi- Beimu and the single herb aqueous extracts following oral delivery in rats. Twelve alkaloids including aconitine, mesaconitine, hypaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypacoitine, neoline, fuziline, talatisamine, chasmanine, peimine and peimisine in rat plasma were simultaneously quantitated by using sensitive ultra-high performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS), with the method developed and fully validated. Plasma concentrations of the twelve alkaloids after administration were determined and pharmacokinetic parameters were compared. Significant differences were observed for all alkaloids except aconitine, mesaconitine and benzoylaconitine for Fuzi- Beimu group in comparison with the single herb group. AUC 0-t and T 1/2 of hypaconitine were increased significantly. AUC 0-t and C max were increased and T max decreased significantly for benzoylmesaconitine and benzoylhypacoitine. Fuziline showed significantly increased AUC 0-t , C max and T max . T 1/2 of neoline was notably increased. T 1/2 and T max were significantly elevated for talatisamine while C max decreased. T max of chasmanine was significantly increased and C max decreased. Extremely significant increase of T max was found for peimisine, and significant increase of T 1/2 for peimine. Results revealed that combined use of Fuzi and Beimu significantly influenced the system exposure and pharmacokinetic behaviors of multiple alkaloids from both

  18. Multiple sclerosis in Germany: data analysis of administrative prevalen