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Sample records for administration oral

  1. 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...... of 5.6 mg nickel (as the sulfate), increased nickel excretion was found over the following 2-3 days. We conclude that consecutive urinary nickel determinations are able to disclose variations in oral intake of nickel....

  2. Voluntary Oral Administration of Losartan in Rats.

    Science.gov (United States)

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  3. Formulation of nimodipine nanocrystals for oral administration.

    Science.gov (United States)

    Li, Jianwen; Fu, Qiang; Liu, Xiaohong; Li, Mo; Wang, Yongjun

    2016-02-01

    The aim of this paper is to optimize nimodipine (NMD) nanocrystals (NCs) for oral administration. The effects of independent process variables (microprecipitation temperature, shearing speed, shearing time, homogenization pressure and number of cycles) on the particle size have been studied. Experiments were conducted to optimize the formulation composition. A single factor exploration was used to screen the primary stabilizers. Then, the selected polymers/surfactants were further optimized using an L9 (3(4)) orthogonal design. The optimal formulation was composed of NMD (0.7 %, w/v), F127 (0.4 %, w/v), HPMC-E5 (0.1 %, w/v), and sodium deoxycholate (0.05 %, w/v) and was rod-shaped as shown by SEM observations, and it had a particle size of 833.3 ± 20.6 nm, determined by laser diffraction. These aqueous NCs were physically stable for 15 days. To further improve the stability, the NCs were freeze-dried. The powder obtained exhibited acceptable flowability and was physically stable for at least 24 months. Additionally, the NMD NCs displayed much higher dissolution profiles than the bulk drug. The pharmacokinetic results showed that the relative bioavailability was 397 % in comparison with Nimotop(®), suggesting that NCs are an efficient strategy for improving the oral bioavailability of poorly water-soluble drugs.

  4. Skeletal growth after oral administration of demineralized bone matrix.

    Science.gov (United States)

    Martínez, J A; Elorriaga, M; Marquínez, M; Larralde, J

    1993-03-01

    Oral administration of bone extracts obtained from bovine demineralized bone matrix to rats has a direct effect on bone metabolism, affecting bone proportions and some markers of bone formation such as bone malate dehydrogenase, serum alkaline phosphatase and serum osteocalcin. Furthermore collagen deposition, bone protein synthesis and nucleic acids content were significantly increased by the treatment.

  5. Intra-oral PTH administration promotes tooth extraction socket healing.

    Science.gov (United States)

    Kuroshima, S; Kovacic, B L; Kozloff, K M; McCauley, L K; Yamashita, J

    2013-06-01

    Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healing. The mandibular first molars were extracted in rats, and subcutaneous PTH was administered intermittently for 7, 14, and 28 days. In a second study, maxillary second molars were extracted, and PTH was administered by either subcutaneous or intra-oral injection to determine the efficacy of intra-oral PTH administration. Healing was assessed by micro-computed tomography and histomorphometric analyses. PTH therapy accelerated the entire healing process and promoted both hard- and soft-tissue healing by increasing bone fill and connective tissue maturation. PTH therapy by intra-oral injection was as effective as subcutaneous injection in promoting tooth extraction socket healing. The findings suggest that PTH therapy promotes tooth extraction socket healing and that intra-oral injections can be used to administer PTH.

  6. Radioprotective effects of ON 01210.Na upon oral administration.

    Science.gov (United States)

    Suman, Shubhankar; Datta, Kamal; Doiron, Kathryn; Ren, Chen; Kumar, Ramesh; Taft, David R; Fornace, Albert J; Maniar, Manoj

    2012-01-01

    ON 01210.Na (Ex-RAD), a chlorobenzylsulfone derivative was investigated for its pharmacologic and radioprotective properties when administered via oral and subcutaneous (SC) routes. The goals of the study were to assess the comparative bioavailability of ON 01210.Na when administered by oral versus SC routes and to demonstrate that the oral drug delivery of ON 01210.Na afforded survival advantage similar to SC dosing. Pharmacokinetics was studied after two doses, 24 h apart, of ON 01210.Na (500 mg/kg) administered to male C3H/Hen mice (7-9 weeks) via SC injection or oral route. The dose response (100 to 750 mg/kg) and survival advantage of ON 01210.Na administered at 24 h and 15 min prior to 7.5 or 8 Gy whole body irradiation from a ¹³⁷Cs source (dose rate 1 Gy/min) were studied in these mice. Effects on the hematopoietic system were investigated by complete blood count and granulocyte-macrophage colony forming unit assay. A significant survival advantage and hematopoietic protection were observed after prophylactic oral ON 01210.Na and results were comparable to SC administration. These findings correlated well with pharmacokinetic data. Both SC and oral ON 01210.Na showed significant survival advantage against radiation toxicity and ON 01210.Na mediated hematopoietic protection plays key role in enhanced survival of mice. Oral administration holds better clinical promise as an effective countermeasure not only for early-responders in a nuclear accident, but also for the at-risk civilian population.

  7. Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

    Science.gov (United States)

    Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

    2004-09-01

    Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and

  8. Distribution of creatinine following intravenous and oral administration to rats.

    Science.gov (United States)

    Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

    1981-05-01

    To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

  9. Systemic uptake of buprenorphine by cats after oral mucosal administration.

    Science.gov (United States)

    Robertson, S A; Taylor, P M; Sear, J W

    2003-05-31

    The plasma concentration of buprenorphine was measured by radioimmunoassay in six female cats after the administration of 0.01 mg/kg (0.033 ml/kg) buprenorphine hydrochloride solution into the side of the cat's mouth. Blood samples were taken through a preplaced jugular catheter before and one, two, four, six, 10, 15, 30, 45 and 60 minutes, and two, four, six, 12 and 24 hours after the dose was administered. The buprenorphine was accepted well by all the cats and did not cause salivation or vomiting. Its median peak plasma concentration was 7.5 ng/ml and was reached after 15 minutes. The pharmacokinetic data were similar to the pharmacokinetic data obtained after the intramuscular and intravenous administration of buprenorphine to cats from the same colony, suggesting that the mucosal route of administration should be as effective as intravenous and intramuscular injections. In addition, the pH of the oral cavity of 26 cats was measured with pH paper, and 100 cat owners were asked their preferred method of administering drugs to cats. The pH of the cats' mouths was between 8 and 9, and the technique preferred by the cat owners was the use of drops placed in the mouth.

  10. Fast disintegrating tablets of nisoldipine for intra-oral administration.

    Science.gov (United States)

    El Maghraby, Gamal M; Elsergany, Ramy N

    2014-09-01

    Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5 min. HPMC-based tablets disintegrated rapidly and released most of the drug in the first 2 min which correlated with the corresponding SD. In contrast, PVP-based tablets disintegrated slowly with gradual dissolution. This can be attributed to the binding effect of PVP. The study developed fast disintegrating tablet for intra-oral administration.

  11. Less mammographic density after nasal versus oral administration of postmenopausal hormone therapy

    NARCIS (Netherlands)

    Dijck, J.A. van; Otten, J.D.M.; Karssemeijer, N.; Kenemans, P.; Verbeek, A.L.M.; Mooren, M.J. van der

    2011-01-01

    ABSTRACT Objective Nasal administration gives a more acute but shorter rise in serum hormone levels than oral administration and may therefore have less effect on the fibroglandular tissue in the breasts. We studied the change in mammographic breast density after nasal vs. oral administration of pos

  12. Pharmacokinetic parameters of meloxicam after its oral administration in goat

    Directory of Open Access Journals (Sweden)

    A R. Wani

    2014-03-01

    Full Text Available Aim: The objective of the present study was to find out the levels of analgesic drug meloxicam in the blood plasma of young goats. The drug was given to them through oral route. Data was used to elucidate the Pharmacokinetic determinants of the drug which were employed to arrive at the dose schedule and frequency of the drug in goats. Materials and Methods: Elaborate pharmacokinetic research of the drug meloxicam was done on 18 to 24 months old, five adult male local goats (Capra hircus of Assam weighing 20 to 25 kg.The drug was given orally at the dose rate of 0.35 mg/kg at the Goat Rearing farm, Guwahati, Assam. Analysis of blood was done by high performance liquid chromatography (HPLC system. Results: The mean values of area under curve (AUC and mean area under curve (AUMC were 3137.488 ± 125.3749 µg.min/ml and 4650460 ± 380892.4744 µg.min2/ml respectively .The mean peak plasma level of meloxicam was 1.972 ± 0.0477 µg/ml at 600 min. The mean values of elimination half life (t1/2β and absorption half life (t1/2Ka were 693±0.00 min and 170.6 ± 17.0076 min respectively. The mean values of volume of distribution (Vd and mean residence time (MRT were 0.114 ± 0.0156 L/kg and 1472.264 ± 63.336 min respectively. The mean value of Tmax was found to be 497 ± 19.8040 min. Following single oral administration the minimum effective therapeutic concentration or minimum effective plasma concentration of meloxicam was detectable up to 1200 min. The bioavailibity (F of the drug was 80.5 ± 10.0150%. Conclusion: These pharmacokinetic determinants were used to determine the frequency and dose schedule of meloxicam in goats. The minimum effective concentration of the drug is 0.7 µg/ml in plasma. To maintain this, an initial loading dose of 0.5 mg/kg body weight should be followed by a maintenance dose of 0.4 mg/kg body weight/10 hour.

  13. HISTOLOGICAL STUDIES OF THE EFFECTS OF ORAL ADMINISTRATION OF ARTESUNATE

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    A.O.Eweka

    2008-01-01

    Full Text Available The histological effect of oral administration of artesunate, commonly used for the treatment of Malaria on the medial geniculate body (MGB of adult wistar rat was carefully studied. The rats of both sexes (n=24, average weight of 210g were randomly assigned into three treatment (n=18 and control (n6 groups.The rats in the treatment group 'A' received 4mg/kg body weight of artesunate base dissolved in distilled water for 3 days. The animals in groups 'B' and 'C' received 4mg/kg body weight of artesunate dissolved in distilled water for the first day and thereafter received 2mg/kg body weight daily for six and thirteen day respectively. The control group D, received equal volume of distilled water daily using the Orogastric tube. The rats were fed with grower's mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria and were given water liberally. The rats were sacrificed on day fourth, eight and fifteenth of the experiment. The medial geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological studies.The histological findings after H&E method indicated that the treated section of the medial geniculate body showed some decreased cellular population, degenerative changes, cellular hypertrophy, with some vacuolations appearing in the stroma.Varying dosage and long administration of artesunate may have some deleterious effects on the neurons of the Medial geniculate body and this may probably have some adverse effects on auditory sensibilities by its deleterious effects on the cells of the medial geniculate body of adult wistar rats. It is therefore recommended that further studies aimed at corroborating these observations be carried out.

  14. Clinical Observation on Treatment of Acquired Paralytic Strabismus by Acupuncture Plus Oral Administration of Chinese Herbs

    Institute of Scientific and Technical Information of China (English)

    元旭红

    2003-01-01

    @@ From June 1996 to June 2002, the author treated 38 cases of acquired paralytic strabismus by acupuncture plus oral administration of Zheng Rong Tang (正容汤), with another 38 cases of acquired paralytic strabismus treated only with oral administration of Chinese herbs as the controls. The results are reported as follows.

  15. Administrators' ratings of competencies needed to prepare preservice teachers for oral deaf education programs.

    Science.gov (United States)

    Lartz, Maribeth N; Litchfield, Sharon K

    Deaf education teacher preparation programs must prepare teachers to staff an increasing number of oral programs. A survey was conducted to determine which competencies administrators of deaf education programs rate as important for teachers in oral programs and to compare ratings of these competencies by oral school administrators to ratings made by administrators of comprehensive deaf and hard of hearing programs. Between the two groups of administrators, six areas of agreement about competencies were found. There were notable differences in the range of ratings between the two groups. These differences were attributed to the roles teachers assume in the two types of programs and the focus of instruction in each type of program.

  16. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

    Science.gov (United States)

    Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

    2005-03-01

    Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

  17. Can TiC nanoparticles produce toxicity in oral administration to rats?

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    Julie Laloy

    2014-01-01

    Conclusion: No sign of toxicity was found after oral administration. TiC was excreted mostly in feces producing mineral absorption alterations. Low traces were retrieved in urine, indicating that TiC can cross the intestinal barrier.

  18. 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 the...

  19. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens

    NARCIS (Netherlands)

    C.B.M. Maassen (Kitty); J.D. Laman (Jon); C. van Holten-Neelen; L. Hoogteijling (L.); L. Groenewegen (Lizet); L. Visser (Lizette); M.M. Schellekens (M.); W.G. Boersma (Wim); H.J.H.M. Claassen (Eric)

    2003-01-01

    textabstractOral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we

  20. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing meyelin antigens

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, van J.C.P.A.; Groenewegen, L.; Hoogteijling, L.; Visser, L.; Boersma, W.J.A.

    2003-01-01

    Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetica

  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...

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

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

    2013-01-01

    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 ......, eliminates the need for fasting without affecting the bioavailability of risedronate or its efficacy....

  3. Lamb deaths associated with administration of oral minerals.

    Science.gov (United States)

    2016-10-22

    Deaths in preweaned lambs associated with administering oral minerals containing copperCongenital malformations in calvesIdiopathic necrotising enteritis in calvesAbomasal obstruction due to trichobezoars in suckled calvesRadial neuropathy (kangaroo gait) in a ewe These are among matters discussed in the disease surveillance report for July 2016 from SAC Consulting: Veterinary Services (SAC C VS).

  4. Relationship between lethal toxicity in oral administration and injection to mice: effect of exposure routes.

    Science.gov (United States)

    Wang, Yu; Ning, Zhong H; Tai, Hong W; Long, Shuang; Qin, Wei C; Su, Li M; Zhao, Yuan H

    2015-03-01

    The lethal toxicity (LD₅₀) in oral administration, intravenous, intraperitoneal, intramuscular and subcutaneous injections were used to investigate relationships of log 1/LD₅₀ from different exposure routes. Regression analysis showed that log 1/LD₅₀ in oral route was related to the toxicity in injection route. This relationship in lethality between the two routes is apparently due to the same mechanisms of the compounds to the same species. However, the scatter in the correlation curve indicates that exposure route is an important factor that influences the relationship. Some compounds with low intestinal absorption exhibit much less toxicity in oral administration than that in the injection route. A systemic bias of log 1/LD₅₀ between oral and injection routes indicates that tissue distribution of compounds between blood and target site is a very rapid process, leading to log 1/LD₅₀ in injection greater than those in oral administration. Although compounds can be metabolized in the body both from oral and injection routes, first-pass metabolism occurs in oral route but not in injection route. This will result in decrease of toxicity in oral route for most compounds as compared with injection route. In addition, experimental uncertainty, differences in gender, and species can also affect relationships of log1/LD₅₀ between exposure routes.

  5. Clinical systemic lupeol administration for canine oral malignant melanoma

    OpenAIRE

    YOKOE, INORU; AZUMA, Kazuo; Hata, Keishi; MUKAIYAMA, TOSHIYUKI; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; ITOH, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2014-01-01

    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperative...

  6. Nursing time study for the administration of a PRN oral analgesic on an orthopedic postoperative unit.

    Science.gov (United States)

    Pizzi, Lois J; Chelly, Jacques E; Marlin, Vanessa

    2014-09-01

    As needed (PRN) oral opioid analgesics are an integral part of many orthopedic postoperative multimodal pain management regimens. However, the unpredictable nature of this dosing method can lead to disruptions in the process of administering the medication, as well as be an interruption to regular nursing activities. This IRB approved quantitative time study tested the hypothesis that a significant amount of nursing time is required in the administration of PRN oral opioid analgesics on a postoperative orthopedic nursing unit. The purpose of this study is to evaluate the time necessary to complete the required steps related to the administration of PRN oral analgesics. Nurses from 28 nursing shifts used a personal digital assistant (PDA) to record the time needed to complete these steps. We determined that 10.9 minutes is the mean time required to administer PRN oral analgesics on this unit. Other time studies have evaluated the medication administration process as a whole. No time studies related to PRN oral analgesic administration have been reported. In phase I of our project, the data were summarized and will be used as a baseline comparison for phase II, in which we will evaluate an oral PCA medication administration system.

  7. Dosage Form Developments of Nanosuspension Drug Delivery System for Oral Administration Route.

    Science.gov (United States)

    Chen, Ang; Shi, Ye; Yan, Zhiqiang; Hao, Hongxun; Zhang, Yong; Zhong, Jian; Hou, Huiming

    2015-01-01

    A large amount of new drug candidates are practically insoluble in aqueous solvents and are even simultaneously poorly soluble in organic solvents. Nanosuspension drug delivery system (DDS) was firstly developed in 1994 and has attracted more and more attention as a formation solution for the poorly soluble drugs. By nansizing the poorly soluble drugs, nanosuspensions have several outstanding advantages for drug delivery. Among many administration routes of drug delivery, oral administration is the most preferred route due to its advantages such as ease of ingestion, versatility to accommodate various types of drug candidates, low production cost, high safety, good patient compliance, and pain avoidance. Current marketed pharmaceutical nanosuspension DDS products are mostly for oral administration. This review is to systematically summarize the nanosuspension DDS dosage form developments of poorly soluble drugs for oral administration use.

  8. 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.

  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.

  10. Clinical systemic lupeol administration for canine oral malignant melanoma.

    Science.gov (United States)

    Yokoe, Inoru; Azuma, Kazuo; Hata, Keishi; Mukaiyama, Toshiyuki; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; Itoh, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperatively at various time points to treat these 11 COMM cases. Of the 11 subjects, 7 exhibited no local recurrence 180 days postoperatively and no severe adverse effects were observed in any of the cases. Furthermore, no distant metastasis was observed during the experimental period. Therefore, systemic lupeol may prevent local tumor progression and distant metastasis and may be a novel adjuvant treatment for the treatment of COMM.

  11. Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Qi; Ting Zhao; Wen-Wen Yang; Guang-Hou Wang; Hua Yua; Hai-Xiao Zhao; Chen Yang; Li-Xin Suna

    2011-01-01

    The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUCo-t, AUCo-∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosting of 50.0 mg/kz.

  12. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

    OpenAIRE

    Mustonen Katja; Niemi Anneli; Raekallio Marja; Heinonen Mari; Peltoniemi Olli AT; Palviainen Mari; Siven Mia; Peltoniemi Marikki; Vainio Outi

    2012-01-01

    Abstract Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers betwee...

  13. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    Science.gov (United States)

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  14. Safe handling and administration considerations of oral anticancer agents in the clinical and home setting.

    Science.gov (United States)

    Lester, Joanne

    2012-12-01

    The use of hormonal, chemotherapeutic, and targeted biologic oral agents has exponentially increased since the early 2000s. Oral therapies have the advantage of persistent exposure of the cytotoxic drug to tumor cells and the tumor environment. The use of oral anticancer agents provides therapeutic drug treatment for patients with cancer in the comfort of their home or alternative settings, such as retirement homes and assisted living or extended-care facilities. Practices to ensure safe storage, handling, administration, and disposal of oral agents are necessary to prevent additional exposure of hazardous substances to the environment, professionals, patients, family members, and caretakers. Providers should consider potential barriers to adherence and compliance, and develop strategies to ensure optimal therapeutic benefit prior to initiation of oral agents.

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

    Directory of Open Access Journals (Sweden)

    Pazianas M

    2013-10-01

    Full Text Available Michael Pazianas,1 Bo Abrahamsen,2,3 Serge Ferrari,4 R Graham G Russell1,5 1The Botnar Research Center and Oxford University Institute of Musculoskeletal Sciences, Oxford, UK; 2Department of Medicine F, Gentofte Hospital, Hellerup, 3Odense Patient data Explorative Network (OPEN Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland; 5Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK Abstract: 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 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, 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, eliminates the need for fasting without affecting the bioavailability of risedronate or its efficacy. Keywords: bisphosphonates, osteoporosis treatment, absorption, EDTA, osteoclasts

  16. Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits.

    Science.gov (United States)

    Astroug, Henri; Simeonova, Roumiana; Kassabova, Lilia V; Danchev, Nikolay; Svinarov, Dobrin

    2010-03-01

    The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits. The pharmacokinetic behaviour of cytisine is studied in male and female New Zealand rabbits after oral and intravenous administration. Cytisine is administered orally (dose of 5 mg/kg b.w.) under fasting condition (12 hours) and intravenously (dose 1 mg/kg b.w.) in the marginal ear vein. Cytisine serum concentrations are measured using a highly selective and sensitive validated HPLC method with UV detection. Linearity of the method is in the range 12-2 400 µg/L; accuracy and precision are both within ± 10%, and the limit of detection is 4 µg/L. Selectivity and stability are also validated. Basic pharmacokinetic parameters of cytisine after single oral and intravenous administration are calculated using TOPFIT software. Pharmacokinetic analysis suggests a rapid but incomplete absorption of cytisine after oral administration.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  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...

  2. Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats.

    Science.gov (United States)

    Albarellos, G A; Montoya, L; Landoni, M F

    2005-09-01

    The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.

  3. Effects of oral administration of type Ⅱ collagen on adjuvant arthritis in rat sand its mechanisms

    Institute of Scientific and Technical Information of China (English)

    胡永秀; 赵文明; 钱娴娟; 张力平

    2003-01-01

    Objective To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly.Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN-γ and TNF-α i n articular steep in rats.Results Oral administration of CⅡ was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CⅡ were stronger than those by Tripterygium Polyglycoside. Oral administration of CⅡ inhibi ted antigen-specific immune response, such as DTH and antibody reaction to CⅡ . In addition, the expression of IFN-γ and TNF-α in joints were locally dow nregulated. Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-γ and TNF-α, and the suppression of cell immunity.

  4. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    Zheng-hong WU; Qi-neng PING; Yi WEI; Jia-ming LAI

    2004-01-01

    AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS:In all the insulin liposomes, the insulin liposomes coated by 0.2 % chitosan (M. 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%±6.0 % of the initial (n=6). The hypoglycemic efficacy lasted for 4 h after oral administration to mice.CONCLUSION: Chitosan-coated liposomes could reduce tryptic digestion on insulin, and enhance enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effects on hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.

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

    Directory of Open Access Journals (Sweden)

    Thalita B. Gagini

    2010-06-01

    Full Text Available 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.

  6. A New Approach to the Oral Administration of Insulin and Other Peptide Drugs

    Science.gov (United States)

    Saffran, Murray; Sudesh Kumar, G.; Savariar, Celin; Burnham, Jeffrey C.; Williams, Frederick; Neckers, Douglas C.

    1986-09-01

    The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

  7. ORAL ADMINISTRATION OF NUTMEG ON MEMORY BOOSTING AND REGAINING IN WISTAR ALBINO RATS

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    G Jissa

    2014-01-01

    Full Text Available Background: This study provides further evidence for improvement of memory by oral consumption of nutmeg. The present study was undertaken with an objective to study the effects of oral administration of nutmeg on memory boosting and regaining. Methods: Here we investigate the influence of oral intake of nutmeg on behavioral task performance by using T-maze and radial arm maze and physiological measures relative to a milk control group. Results: We have observed significant memory boosting and memory regaining effects of nutmeg when administered orally. This effect may be due to facilitation of acetylcholine activity by decreasing acetylcholinesterase activity of nutmeg. Hence we recommend further research in this area by investigating compound metabolism to optimize quantification of memory performance following nutmeg consumption.

  8. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    Science.gov (United States)

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease.

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

    Directory of Open Access Journals (Sweden)

    Gabriela A. Albarellos

    2013-02-01

    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.

  10. Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

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    Saburo Minami

    2012-08-01

    Full Text Available D-Glucosamine hydrochloride (GlcN∙HCl is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β.

  11. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

    Directory of Open Access Journals (Sweden)

    Nagelschmitz J

    2014-03-01

    Full Text Available J Nagelschmitz,1 M Blunck,1 J Kraetzschmar,1 M Ludwig,1 G Wensing,1 T Hohlfeld2 1Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany; 2Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany Background: The pharmacology of single doses of acetylsalicylic acid (ASA administered intravenously (250 or 500 mg or orally (100, 300, or 500 mg was evaluated in a randomized, placebo-controlled, crossover study. Methods: Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results: A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D and the geometric mean dose-corrected area under the curve (AUC0–∞/D were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively. Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001 at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion: This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing

  12. Immunomodulation of Experimental Autoimmune Encephalomyelitis by Oral Administration of Copolymer 1

    Science.gov (United States)

    Teitelbaum, Dvora; Arnon, Ruth; Sela, Michael

    1999-03-01

    The activity of copolymer 1 (Cop 1, Copax-one, glatiramer acetate) in suppressing experimental autoimmune encephalomyelitis (EAE) and in the treatment of multiple sclerosis patients when injected parenterally has been extensively demonstrated. In the present study we addressed the question of whether Cop 1 can induce oral tolerance to EAE similar to myelin basic protein (MBP). We now have demonstrated that oral Cop 1 inhibited EAE induction in both rats and mice. Furthermore, oral Cop 1 was more effective than oral MBP in suppressing EAE in rats. The beneficial effect of oral Cop 1 was found to be associated with specific inhibition of the proliferative and Th1 cytokine secretion responses to MBP of spleen cells from Cop 1-fed mice and rats. In all of these assays, oral Cop 1 was more effective than oral MBP. The tolerance induced by Cop 1 could be adoptively transferred with spleen cells from Cop 1-fed animals. Furthermore, Cop 1-specific T cell lines, which inhibit EAE induction in vivo, could be isolated from the above spleen cells. These T cell lines secrete the anti-inflammatory cytokines IL-10 and transforming growth factor type β , but not IL-4, in response to both Cop 1 and MBP. In conclusion, oral Cop 1 has a beneficial effect on the development of EAE that is associated with down-regulation of T cell immune responses to MBP and is mediated by Th2/3 type regulatory cells. These results suggest that oral administration of Cop 1 may modulate multiple sclerosis as well.

  13. Early effects of oral administration of omeprazole and roxatidine on intragastric pH

    Institute of Scientific and Technical Information of China (English)

    Hiroshi IIDA; Masato YONEDA; Tomoko KOIDE; Hirokazu TAKAHASHI; Chikako TOKORO; Ayumu GOTO; Yasunobu ABE; Noritoshi KOBAYASHI; Kensuke KUBOTA; Eiji GOTOH; Shin MAEDA; Shingo KATO; Atsushi NAKAJIMA; Masahiko INAMORI; Yusuke SEKINO; Eiji SAKAI; Takashi UCHIYAMA; Hiroki ENDO; Kunihiro HOSONO; Yasunari SAKAMOTO; Koji FUJITA

    2012-01-01

    Objective:The ideal medication for the treatment of acid-related diseases,e.g.,peptic ulcers,stressrelated gastric bleeding,functional dyspepsia,and gastroesophageal reflux disease,should have a rapid onset of action to promote hemostasis and relieve the symptoms.The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor,omeprazole 20 mg,and an H2-receptor antagonist,roxatidine 75 mg.Methods:Ten Helicobacterpylori-negative male subjects participated in this randomized,two-way crossover study.Intragastric pH was monitored continuously for 6 h after single oral administration of omeprazole 20 mg and roxatidine 75 mg.Each administration was separated by a 7-d washout period.Results:During the 6-h study period,the average pH after administration of roxatidine was higher than that after administration of omeprazole (median:4.45 vs.2.65; P=0.0367).Also during the 6-h study period,a longer duration of maintenance at pH above 2,5,and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg (median:90.6% vs.55.2%,P=0.0284; 43.7% vs.10.6%,P=0.0125; 40.3% vs.3.3%,P=0.0125;respectively).Conclusions:In Helicobacter pylori-negative healthy male subjects,oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.

  14. Oral ondansetron administration in emergency departments to children with gastroenteritis: an economic analysis.

    Directory of Open Access Journals (Sweden)

    Stephen B Freedman

    2010-10-01

    Full Text Available BACKGROUND: The use of antiemetics for children with vomiting is one of the most controversial decisions in the treatment of gastroenteritis in developed countries. Ondansetron, a selective serotonin receptor antagonist, has been found to be effective in improving the success of oral rehydration therapy. However, North American and European clinical practice guidelines continue to recommend against its use, stating that evidence of cost savings would be required to support ondansetron administration. Thus, an economic analysis of the emergency department administration of ondansetron was conducted. The primary objective was to conduct a cost analysis of the routine administration of ondansetron in both the United States and Canada. METHODS AND FINDINGS: A cost analysis evaluated oral ondansetron administration to children presenting to emergency departments with vomiting and dehydration secondary to gastroenteritis from a societal and health care payer's perspective in both the US and Canada. A decision tree was developed that incorporated the frequency of vomiting, intravenous insertion, hospitalization, and emergency department revisits. Estimates of the monetary costs associated with ondansetron use, intravenous rehydration, and hospitalization were derived from administrative databases or emergency department use. The economic burden in children administered ondansetron plus oral rehydration therapy was compared to those not administered ondansetron employing deterministic and probabilistic simulations. We estimated the costs or savings to society and health care payers associated with the routine administration of ondansetron. Sensitivity analyses considered variations in costs, treatment effects, and exchange rates. In the US the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations annually. At the current average wholesale price, its routine administration

  15. Oral administration of Bifidobacterium longum ameliorates influenza virus infection in mice.

    Science.gov (United States)

    Iwabuchi, Noriyuki; Xiao, Jin-Zhong; Yaeshima, Tomoko; Iwatsuki, Keiji

    2011-01-01

    We investigated whether the oral administration of Bifidobacterium longum BB536 could ameliorate influenza virus (IFV) infection in a mice model. Mice were orally administrated BB536 or saline for 2 weeks and then infected with IFV. Orally administered BB536 significantly alleviated symptoms, reduced the loss of body weight, and inhibited viral proliferation in the lungs relative to the control group findings. Histopathological findings in the lungs were improved in the BB536 group compared to control group findings. There was no significant difference in the levels of interleukin-6 (IL-6), interferon-γ (IFN-γ), IL-10 and IL-12p40 in the lungs between the groups, but the levels of IL-6 and IFN-γ were lower (p=0.076, 0.103, respectively) in the BB536 group compared with those of control group. The levels of IL-6 and IL-10 correlated significantly with the values of weight loss, and the levels of IFN-γ correlated with the virus titers in the lungs. These results suggested the potential of the oral administration of BB536 in ameliorating IFV infection and the possible involvement of anti-inflammatory effects of BB536 in the anti-infection effects against IFV.

  16. 口服给药流程的改进%The improvment of oral administration process

    Institute of Scientific and Technical Information of China (English)

    黄燕萍; 罗永梅; 王攀峰

    2014-01-01

    The traditional process of oral administration has some disadvantages, easily resulting in medication errors. This paper described a new process of oral administration based on wireless network, mobile nurses work station, PDA and automatic oral drug dispensing system. This automated and informational process increased the quality and efifciency of oral administration and promoted medication safety.%传统口服给药流程存在一些弊端,容易导致给药差错的发生。本文介绍了依托医院无线网络、移动护士工作站、PDA以及口服摆药机建立起来的以患者为中心的新型口服给药流程。该流程实现了口服给药的信息化与自动化,优化了护理工作流程,提高了口服给药的质量与效率,保障了口服给药的安全性与时效性,促进了护理质量持续改进,值得推广。

  17. 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

    2016-11-02

    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.Mucosal Immunology advance online publication 2 November 2016. doi:10.1038/mi.2016.95.

  18. Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration.

    Science.gov (United States)

    Farré, M; Roset, P N; Llorente, M; Márquez, M; Albet, C; Pérez, J A; Herrero, E; Ortíz, J A

    1997-06-01

    Dotarizine is a new diphenylmethylpiperazine derivative with Ca2+ channel blocking properties and inhibitory effects on 5-HT2A and 5-HT2C receptors. Previous pilot studies in healthy volunteers demonstrated a good tolerability after single and multiple dosing. Dotarizine appeared to be rapidly and extensively metabolized to an active compound (FI-6020). We aimed to study the physiologic, subjective and psychomotor acute effects of oral dotarizine after single dose administration, to evaluate the tolerability and safety after multiple dosing over 2 weeks, and to study the pharmacokinetic parameters and linearity after single and multiple administration. Two different studies were carried out in 2 groups of 8 healthy male volunteers. Oral single doses of dotarizine 50, 100 and 200 mg were administered in a randomized, double-blind, crossover, placebo-controlled trial. Oral doses of 50 mg twice daily were administered in an open trial over 14 days. Drug effect assessments included vital signs, collection of adverse events, ECG and blood and urine safety evaluations, subjective effects, psychomotor performance tasks and blood sampling. Dotarizine and its metabolite were determined by gas chromatography with N-P detector. The results showed a good tolerability of dotarizine after single oral doses as well as multiple oral doses over 14 days. No clinically relevant adverse events were reported during the study. The highest single dose (200 mg) produced a slight increase in sedation-related symptoms as well as a slight impairment in psychomotor performance tasks. Dotarizine and its major metabolite proved linear kinetics at single doses. The administration of oral doses of dotarizine 50 mg b.i.d. reached the steady state after the 7th day of treatment. The pharmacokinetic parameters remained similar from day 7 to day 14. The terminal elimination half-life of dotarizine and its metabolite appeared to be between 7 and 12 h.

  19. 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.

  20. Single- and multiple-dose pharmacokinetics of marbofloxacin after oral administration to rabbits.

    Science.gov (United States)

    Carpenter, James W; Pollock, Christal G; Koch, David E; Hunter, Robert P

    2009-04-01

    OBJECTIVE-To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period. ANIMALS-8 healthy 9-month-old female New Zealand White rabbits. PROCEDURES-Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods. RESULTS-After oral administration, mean +/- SD area under the curve was 10.50 +/- 2.00 microg.h/mL and 10.90 +/- 2.45 microg.h/mL, maximum plasma concentration was 1.73 +/- 0.35 microg/mL and 2.56 +/- 0.71 microg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.

  1. 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.

  2. The absorption and metabolism of a single L-menthol oral versus skin administration: Effects on thermogenesis and metabolic rate.

    Science.gov (United States)

    Valente, Angelica; Carrillo, Andres E; Tzatzarakis, Manolis N; Vakonaki, Elena; Tsatsakis, Aristidis M; Kenny, Glen P; Koutedakis, Yiannis; Jamurtas, Athanasios Z; Flouris, Andreas D

    2015-12-01

    We investigated the absorption and metabolism pharmacokinetics of a single L-menthol oral versus skin administration and the effects on human thermogenesis and metabolic rate. Twenty healthy adults were randomly distributed into oral (capsule) and skin (gel) groups and treated with 10 mg kg(-1) L-menthol (ORALMENT; SKINMENT) or control (lactose capsule: ORALCON; water application: SKINCON) in a random order on two different days. Levels of serum L-menthol increased similarly in ORALMENT and SKINMENT (p > 0.05). L-menthol glucuronidation was greater in ORALMENT than SKINMENT (p  0.05). Participants reported no cold, shivering, discomfort, stress or skin irritation. We conclude that a single L-menthol skin administration increased thermogenesis and metabolic rate in humans. These effects are minor following L-menthol oral administration probably due to faster glucuronidation and greater blood menthol glucuronide levels.

  3. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  4. Administração oral de piperina em frangos de corte Piperine oral administration on broiler' chikens

    Directory of Open Access Journals (Sweden)

    Verônica da Silva Cardoso

    2009-08-01

    Full Text Available O efeito tóxico da piperina, principal amida presente em diversas espécies de pimenta, foi avaliada em frangos de corte por meio da administração oral (0,00, 1,12, 2,25 e 4,5mg kg-1 peso vivo por 14 dias consecutivos. Foram empregados 60 pintos machos (Cobb Avian 48 com sete dias de idade, distribuídos aleatoriamente em quatro grupos experimentais (n=15. Foram avaliados parâmetros como: ganho de peso, peso relativo do fígado e alterações hematológicas e anatomopatológicas. A administração oral de piperina não interferiu no ganho de peso ou no peso relativo do fígado, além de não promover alteração no tamanho e na coloração dos órgãos ou no aparecimento de lesões de parênquima e nas mucosas do órgão. Todavia, alterações histopatológicas dose-dependentes foram observadas. A piperina não foi capaz de alterar significativamente os parâmetros hematológicos analisados, com exceção do leucograma, em que as doses de 1,12mg e 2,25mg kg-1 promoveram aumento do número de heterófilos e do número total de leucócitos, respectivamente. Os resultados sugerem que a dose oral de 1,12mg de piperina por quilo não é tóxica para frangos de corte, sendo semelhante aos resultados obtidos para ratos e camundongos. Além disso, constatou-se a capacidade da piperina em aumentar o número total de leucócitos circulantes a partir da dose de 2,25mg kg-1 nessa espécie animal.The toxic effect of piperine, the main amide compound of different pepper species, was evaluated on broiler chickens by oral administration at 0.00, 1.12, 2.25 and 4.50mg kg-1 concentrations for 14 days. Sixty seven days old male chicks (Cobb Avian 48 randomly allocated to four experimental groups (n=15 were used in this work. Parameters such as: body weight gain, liver relative weight, hematological and anatomopathological alterations were analyzed. The oral route administration did not interfere on weight gain or liver relative weight, as well as, any

  5. Early effects of oral administration of omeprazole and roxatidine on intragastric pH

    OpenAIRE

    2012-01-01

    Objective: The ideal medication for the treatment of acid-related diseases, e.g., peptic ulcers, stress-related gastric bleeding, functional dyspepsia, and gastroesophageal reflux disease, should have a rapid onset of action to promote hemostasis and relieve the symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor, omeprazole 20 mg, and an H2-receptor antagonist, roxatidine 75 mg. Methods:...

  6. Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    Yue YUAN; Xiao-yan CHEN; San-ming LI; Xiu-yan WEI; Hui-min YAO; Da-fang ZHONG

    2009-01-01

    Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs.Methods:The experiment was a two-period,crossover design using 6 Beagle dogs.Meloxicam tablets were administered orally at a dose of 0.31 mg/kg,and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg.Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS).The pharmacokinetic parameters were calculated using the Topfit 2.0 program.Results:The pharmacokinetic results showed that AUCo-t (23.9±8.26 μg·h-mL-1) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 μg·h-mL-1).In contrast,the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery.The synovial fluid concentration in the treated leg was much higher than that in the untreated leg,whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.Conclusion:The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue.This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point.Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

  7. 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.

  8. 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 < 0.0330) after topical application (992 ng g−1 [95% CI 482, 1503], 944 [95% CI 481, 1407], 492 [95% CI 248, 735], and 455 [95% CI 153, 756], respectively) than after oral administration (150 ng g−1 [95% CI 84, 217], 186 [95% CI 118, 254], 82 [95% CI 49, 116],and 221 [95% CI, 135, 307], respectively). Conclusion Topical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  9. Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats.

    Science.gov (United States)

    Carceles, C M; Escudero, E; Vicente, M S; Serrano, J M; Carli, S

    1995-12-01

    The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two-compartment model. Amoxicillin had a greater distribution volume (0.19 +/- 0.01 l/kg) than clavulanic acid (0.15 +/- 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one-compartment model with first-order absorption. Elimination half-lives were twice as long after oral (2.15 +/- 0.20 h and 1.94 +/- 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 +/- 0.16 h and 0.86 +/- 0.09, respectively). An apparent 'flip-flop' situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.

  10. 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.

  11. Molecular mechanism of immune response induced by foreign plasmid DNA after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study immune response induced by foreign plasmid DNA after oral administration in mice.METHODS: Mice were orally administered with 200 μg of plasmid pcDNA3 once and spleen was isolated 4 h and 18 h after administration. Total RNA was extracted from spleen and gene expression profile of BALB/c mice spleen was analyzed by using Affymetrix oligonucleotide GeneChip. Functional cluster analysis was conducted by GenMAPP software.RESULTS: At 4 h and 18 h after oral plasmid pcDNA3 administration, a number of immune-related genes,including cytokine and cytokine receptors, chemokines and chemokine receptor, complement molecule,proteasome, histocompatibility molecule, lymphocyte antigen complex and apoptotic genes, were up-regulated. Moreover, MAPPFinder results also showed that numerous immune response processes were up-regulated. In contrast, the immunoglobulin genes were down-regulated.CONCLUSION: Foreign plasmid DNA can modulate the genes expression related to immune system via the gastrointestinal tract, and further analysis of the related immune process may help understand the molecular mechanisms of immune response induced by foreign plasmid via the gastrointestinal tract.

  12. 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.

  13. Oral self-administration of buprenorphine in the diet for analgesia in mice.

    Science.gov (United States)

    Molina-Cimadevila, M J; Segura, S; Merino, C; Ruiz-Reig, N; Andrés, B; de Madaria, E

    2014-07-01

    Postsurgical oral self-administration of analgesics in rodents is an interesting technique of providing analgesia, avoiding the negative effects of manipulation. Several strategies, using gelatin or nutella, have already been described. However, rodents require some habituation period to reach a good intake because of their neophobic behavior. The current study aimed to explore whether buprenorphine when mixed with an extruded diet offers a potential treatment option in the pain management of mice using a triple approach: by measuring the spontaneous intake in healthy animals; by using the hot-plate test; and finally by assessing the drug's ability to provide postoperative analgesia in a surgical intervention of moderate severity (intra-utero electroporation). Mice consumed during 20 hours, similar amounts of extruded diet alone, mixed with glucosaline, and mixed with buprenorphine (0.03 mg per pellet) or meloxicam (0.25 mg per pellet) both of which were diluted in glucosaline, showing that no neophobia was associated with these administrations. Relative increase from baseline latency (% maximal possible effect) in the hot-plate test at 20 h of administration was significantly higher for oral buprenorphine in diet 0.03 mg/pellet, and diet 0.15 mg/pellet, compared with placebo and no differences were found between those oral administrations and subcutaneous buprenorphine 0.1 mg/kg measured 3 h later. The treatment was also effective in attenuating the reductions in food consumption and body weight that occur after surgery. These data suggest that providing buprenorphine with the diet is a feasible and effective way of self-administration of analgesia in mice and does not cause neophobia and may easily contribute to the refinement of surgical procedures.

  14. Growth hormone, ghrelin and peptide YY secretion after oral glucose administration in healthy and obese women.

    Science.gov (United States)

    Outeiriño-Blanco, E; Garcia-Buela, J; Sangiao-Alvarellos, S; Pertega-Diaz, S; Martinez-Ramonde, T; Cordido, F

    2011-07-01

    The mechanism of the altered GH secretion in obesity is unclear. There is evidence that oral glucose (OG) administration initially decreases and subsequently stimulates GH secretion. Ghrelin is a peptide that displays strong growth hormone-releasing activity. Its physiological importance on GH regulation is unclear. Our aim was to study fasting GH concentrations and their response to OG administration in relation with ghrelin secretion in obese and healthy women, in order to elucidate the hypothetical participation of ghrelin on post-oral glucose GH secretion. 36 women were included in the study. After an overnight fast, 75 g of oral glucose was administered; glucose, insulin, ghrelin, and PYY (1-36) were obtained at baseline and during 300 min. The area under the curve between 0 and 300 min (AUC) of GH μ/l·min) was lower in obese patients than in controls; 262.5±57.5 vs. 534.9±95.6, p=0.01, for obese and controls respectively. GH peak (μg/l) was lower in obese patients than in controls; 3.7±0.7 vs. 7.1±1.0, p=0.012, for obese and controls, respectively. The AUC of total ghrelin (pg/ml·min) was lower in obese patients than in controls; 233,032±12,641 vs. 333,697±29,877, p=0.004, for the obese patients and controls respectively. PYY (1-36) was similar in obese and healthy women after OG. There were significant correlations between the different indices of post-oral glucose GH and ghrelin secretion. These data suggest that ghrelin is a physiological regulator of GH in the post-oral glucose state, and the decreased ghrelin secretion could be one of the mechanisms responsible for the altered GH secretion in obesity.

  15. 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.

  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

    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.

  17. Premedication with midazolam in intellectually disabled dental patients: Intramuscular or oral administration? A retrospective study

    Science.gov (United States)

    Boku, Aiji; Sugimura, Mitsutaka; Oyamaguchi, Aiko; Inoue, Mika; Niwa, Hitoshi

    2016-01-01

    Background The use of midazolam for dental care in patients with intellectual disability is poorly documented. The purpose of this study was to determine which method of premedication is more effective for these patients, 0.15 mg/kg of intramuscular midazolam or 0.3 mg/kg of oral midazolam. Material and Methods This study was designed and implemented as a non-randomized retrospective study. The study population was composed of patients with intellectual disability who required dental treatment under ambulatory general anesthesia from August 2009 through April 2013. Patients were administered 0.15 mg/kg of midazolam intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable was the method of midazolam administration. The outcome variables measured were Observer’s Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of cooperation when entering the operation room and for venous cannulation, post-anesthetic agitation and recovery time. Results Midazolam was administered intramuscularly in 23 patients and orally in 21 patients. More patients were successfully sedated with no resistance behavior during venous cannulation in Group PO than in Group IM (p=0.034). There were no differences in demographic data and other variables between the groups. Conclusions The results of this study suggest that oral premedication with 0.3 mg/kg of midazolam is more effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of patient resistance to venous cannulation. If both oral and intramuscular routes of midazolam are acceptable in intellectually disabled patients, the oral route is recommended. Key words:Premedication, midazolam, intellectual disability. PMID:27031068

  18. Effect of repeated oral administration on taurocholate on hepatic excretory function in the rat.

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1981-07-01

    The effect of repeated administration of taurocholate on bile acid pool size, biliary composition and biliary excretory capacity for bile acids and two xenobiotics was determined. The bile acid pool was increased 50 to 60% by oral administration of sodium taurocholate (300--900 mg/kg, 10 ml/kg) every 12 hr for 2 days to male Sprague-Dawley rats. Bile flow, biliary excretion of bile acids, cholesterol and phospholipid and the concentrations of phospholipid and bile acids in bile were increased in rats treated with 750 mg of taurocholate per kg. No effect was observed on Na+,K+ or Cl- levels. The biliary transport maximum for taurocholate was increased by 30% in rats treated with 750 mg/kg. In contrast, the plasma disappearance and biliary excretion of phenol-3,6-dibromphthalein and ouabain were not affected by taurocholate administration.

  19. Liposomes as a carrier for oral administration of insulin: effect of formulation factors.

    Science.gov (United States)

    Choudhari, K B; Labhasetwar, V; Dorle, A K

    1994-01-01

    The present work was undertaken to study the effect of liposome formulation factors on its efficiency as a carrier for oral administration of insulin. The insulin-liposomes were prepared by two methods: solvent evaporation hydration and solvent spherule evaporation, with various variables such as concentration of insulin (I), lecithin (L), cholesterol (C), and Tween-80 (T). It was found that the insulin-liposomes when administered orally could produce hypoglycaemia. Variation in liposome composition was found to affect the efficiency of liposome as a carrier for oral administration of insulin. A liposome system containing L, 100 mg; C, 20 mg; I, 150 units; T, 1 per cent v/v, and prepared by the solvent spherule evaporation method was found to be most effective. The effect of insulin-liposome had prolonged action in diabetes-induced rabbits compared with that in normal rabbits. The results of the insulin-liposome system were comparable with the action of 1 unit of insulin/kg administered subcutaneously.

  20. Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women.

    Science.gov (United States)

    Paesano, Rosalba; Torcia, Francesco; Berlutti, Francesca; Pacifici, Enrica; Ebano, Valeria; Moscarini, Massimo; Valenti, Piera

    2006-06-01

    Iron deficiency anemia (IDA) during pregnancy continues to be of world-wide concern. IDA is a risk factor for preterm delivery and subsequent low birth weight, and possibly for poor neonatal health. Iron supplementation in pregnancy is a widely recommended practice, yet intervention programs have met with many controversies. In our study, 300 women at different trimesters of pregnancy were enrolled in a trial of oral administration of ferrous sulfate (520 mg once a day) or 30% iron-saturated bovine lactoferrin (bLf) (100 mg twice a day). Pregnant women refusing treatment represented the control group. In this group hemoglobin and total serum iron values measured after 30 d without treatment decreased significantly, especially in women at 18-31 weeks of pregnancy. In contrast, after 30 d of oral administration of bLf, hemoglobin and total serum iron values increased and to a greater extent than those observed in women treated orally for 30 d with ferrous sulfate, independently of the trimester of pregnancy. Unlike ferrous sulfate, bLf did not result in any side effects. These findings lead us to hypothesize that lactoferrin could influence iron homeostasis directly or through other proteins involved in iron transport out of the intestinal cells into the blood.

  1. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

    Directory of Open Access Journals (Sweden)

    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.

  2. Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

    OpenAIRE

    Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

    2008-01-01

    Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist.

  3. 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...

  4. 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

  5. Dose-dependent pharmacokinetics and brain penetration of rufinamide following intravenous and oral administration to rats.

    Science.gov (United States)

    Gáll, Zsolt; Vancea, Szende; Szilágyi, Tibor; Gáll, Orsolya; Kolcsár, Melinda

    2015-02-20

    Rufinamide is a third-generation antiepileptic drug, approved recently as an orphan drug for the treatment of Lennox-Gastaut syndrome. Although extensive research was conducted, its pharmacokinetics in rats was not described. This work addresses that area by describing in a rapid pharmacokinetic study the main pharmacokinetic properties of rufinamide at three different doses of 1 mg/kg body weight (bw), 5 mg/kg bw, and 20 mg/kg bw. Furthermore, total brain concentrations of the drug were determined in order to characterize its brain-to-plasma partition coefficient. Adult Wistar male rats, weighing 200-450 g, were administered rufinamide by intravenous and oral routes. Rufinamide concentrations from plasma samples and brain tissue homogenate were determined using a liquid chromatography-mass spectrometric method and pharmacokinetic parameters were calculated. The mean half-life was between 7 and 13 h, depending on route of administration--intravenously administered drug was eliminated faster than orally administered drug. Mean (S.E.M.) total plasma clearance was 84.01 ± 3.80 ml/h/kg for intravenous administration, while the apparent plasma clearance for oral administration was 95.52 ± 39.45 ml/h/kg. The mean (S.E.M.) maximum plasma concentration reached after oral administration of 1 mg/kg bw and 5 mg/kg bw was 0.89 ± 0.09 μg/ml and 3.188 ± 0.71 μg/ml, respectively. The median (range) time to reach maximum plasma concentration (t(max)) was 4 (2-8)h. Mean (S.E.M.) brain-to-plasma concentration ratio of rufinamide was 0.514 ± 0.036, consistent with the brain-to-plasma ratio calculated from the area under curves (AUC(0-t)) of 0.441 ± 0.047. No influence of dose, route of administration, or post-dosing time was observed on brain-to-plasma ratio.

  6. 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...... assessed the overall survival (OS) and disease-free survival (DFS) of patients treated with adjuvant i.v. vinorelbine or p.o. vinorelbine, in combination with i.v. cisplatin. MATERIALS AND METHODS: We reviewed two time-separated cohorts of patients referred to the Department of Oncology at Aarhus...... 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...

  7. GLC determination of plasma drug levels after oral administration of clorazepate potassium salts.

    Science.gov (United States)

    Hoffman, D J; Chun, A H

    1975-10-01

    Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs.

  8. Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat.

    Science.gov (United States)

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

    2009-01-01

    The objective of this work was to study the disposition kinetics of valine-valine-acyclovir (VVACV), a dipeptide ester prodrug of acyclovir following intravenous and oral administrations in rat. A validated LC-MS/MS analytical method was developed for the analysis VVACV, Valine-Acyclovir (VACV), and Acyclovir (ACV) using a linear Ion Trap Quadrupole. ACV was administered orally for comparison purpose. In the VVACV group, both blood and urine samples and in the ACV group only blood samples were collected. All the samples were analyzed using LC-MS/MS. The LLOQ for ACV, VACV, and VVACV were 10, 10, and 50 ng/ml, respectively. Relevant pharmacokinetic parameters were obtained by non-compartmental analyses of data with WinNonlin. Following i.v. administration of VVACV, AUC(0-inf) (min*µM) values for VVACV, VACV, and ACV were 55.06, 106, and 466.96, respectively. The AUC obtained after oral administration of ACV was 178.8. However, following oral administration of VVACV, AUC(0-inf) values for VACV and ACV were 89.28 and 810.77, respectively. Thus the exposure of ACV obtained following oral administration of VVACV was almost 6-fold higher than ACV. This preclinical pharmacokinetic data revealed that VVACV has certainly improved the oral bioavailability of ACV and is an effective prodrug for oral delivery of ACV.

  9. 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.

  10. Oral administration of aflatoxin G₁ induces chronic alveolar inflammation associated with lung tumorigenesis.

    Science.gov (United States)

    Liu, Chunping; Shen, Haitao; Yi, Li; Shao, Peilu; Soulika, Athena M; Meng, Xinxing; Xing, Lingxiao; Yan, Xia; Zhang, Xianghong

    2015-02-03

    Our previous studies showed oral gavage of aflatoxin G₁ (AFG₁) induced lung adenocarcinoma in NIH mice. We recently found that a single intratracheal administration of AFG₁ caused chronic inflammatory changes in rat alveolar septum. Here, we examine whether oral gavage of AFG₁ induces chronic lung inflammation and how it contributes to carcinogenesis. We evaluated chronic lung inflammatory responses in Balb/c mice after oral gavage of AFG₁ for 1, 3 and 6 months. Inflammatory responses were heightened in the lung alveolar septum, 3 and 6 months after AFG₁ treatment, evidenced by increased macrophages and lymphocytes infiltration, up-regulation of NF-κB and p-STAT3, and cytokines production. High expression levels of superoxide dismutase (SOD-2) and hemoxygenase-1 (HO-1), two established markers of oxidative stress, were detected in alveolar epithelium of AFG₁-treated mice. Promoted alveolar type II cell (AT-II) proliferation in alveolar epithelium and angiogenesis, as well as increased COX-2 expression were also observed in lung tissues of AFG₁-treated mice. Furthermore, we prolonged survival of the mice in the above model for another 6 months to examine the contribution of AFG₁-induced chronic inflammation to lung tumorigenesis. Twelve months later, we observed that AFG₁ induced alveolar epithelial hyperplasia and adenocarcinoma in Balb/c mice. Up-regulation of NF-κB, p-STAT3, and COX-2 was also induced in lung adenocarcinoma, thus establishing a link between AFG₁-induced chronic inflammation and lung tumorigenesis. This is the first study to show that oral administration of AFG₁ could induce chronic lung inflammation, which may provide a pro-tumor microenvironment to contribute to lung tumorigenesis.

  11. 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.

  12. Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

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    Odensvik K

    2003-12-01

    Full Text Available The pharmacokinetics and the prostaglandin (PG synthesis inhibiting effect of flunixin were determined in 6 Norwegian dairy goats. The dose was 2.2 mg/kg body weight administered by intravenous (i.v., intramuscular (i.m. and oral (p.o. routes using a cross-over design. Plasma flunixin content was analysed by use of liquid chromatography and the PG synthesis was evaluated by measuring plasma 15-ketodihydro-PGF2α by a radioimmuno-assay. Results are presented as median (range. The elimination half-lives (t1/2·λ were 3.6 (2.0–5.0, 3.4 (2.6–6.8 and 4.3 (3.4–6.1 h for i.v., i.m. and p.o. administration, respectively. Volume of distribution at steady state (Vdss was 0.35 (0.23–0.41 L/kg and clearance (CL, 110 (60–160 mL/h/kg. The plasma concentrations after oral administration showed a double-peak phenomenon with the two peaks occurring at 0.37 (0.25–1 and 3.5 (2.5–5.0 h, respectively. Both peaks were in the same order of magnitude. Bioavailability was 79 (53–112 and 58 (35%–120% for i.m. and p.o. administration, respectively. 15-Ketodihydro-PGF2α plasma concentrations decreased after flunixin administration independent of the route of administration.

  13. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

    Science.gov (United States)

    Jenkins, Eileen K; Lee-Fowler, Tekla M; Angle, T Craig; Behrend, Ellen N; Moore, George E

    2016-08-01

    OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs.

  14. 5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

    Institute of Scientific and Technical Information of China (English)

    Yongquan Pan; Peng Zhang; Junqing Yang; Qiang Su

    2010-01-01

    A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum.In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-lipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage andspatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

  15. 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

  16. 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...... effective than cimetidine alone. These results show that a combination of an agent inhibiting gastric acid secretion and the cytoprotective and growth-stimulating peptide EGF/URO seems to be more effective with regard to duodenal ulcer healing than individual administration of the two substances. Synthetic...

  17. Prevention of Osteoporosis by Oral Administration of Phytate-Removed and Deamidated Soybean β-Conglycinin

    Directory of Open Access Journals (Sweden)

    Makoto Akao

    2015-01-01

    Full Text Available Phytate-removed and deamidated soybean β-conglycinin (PrDS prepared by ion-exchange resins was supplemented to be 4% in the diet administered to ovariectomized rats to investigate its preventive effect on osteoporosis. The apparent calcium absorption rate decreased following ovariectomy and was not replenished by oral administration of phytate-removed soybean β-conglycinin (PrS or casein. On the other hand, administration of PrDS restored the calcium absorption rate to the same level as the sham group. Markers of bone resorption, such as serum parathyroid hormone (PTH and urinary deoxypyridinoline (DPD, increased, and the bone mineral density and breaking stress decreased following ovariectomy. However, PrDS supplementation suppressed the changes caused by the decrease in calcium absorption from the small intestine. Therefore, PrDS supplementation shows promise for the prevention of postmenopausal osteoporosis.

  18. Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

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    Mustonen Katja

    2012-09-01

    Full Text Available Abstract Background Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO and intra muscular (IM routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs. Methods Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (Frel was determined for S and R –ketoprofen. Results S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM, and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM. The mean (± SD relative bioavailability (PO compared to IM was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively. Conclusions Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of

  19. Pharmacokinetic evaluation of visnagin and Ammi visnaga aqueous extract after oral administration in rats.

    Science.gov (United States)

    Haug, Karin G; Weber, Benjamin; Hochhaus, Guenther; Butterweck, Veronika

    2012-11-01

    The furanochromone visnagin is one of the main compounds of Ammi visnaga L. (syn. Khella) with potential effects on kidney stone prevention. After determination of the pharmacokinetic properties of visnagin after intravenous bolus administration in rats, the aim of the present study was to evaluate the pharmacokinetic properties of visnagin and an aqueous Ammi visnaga extract after oral administration in rats. In two separate experiments, three doses of visnagin (2.5, 5, and 10 mg/kg) solubilized in 25 % Captisol® and three doses of Ammi visnaga extract (standardized on visnagin and containing equivalent amounts of visnagin) were administered by oral gavage to male Sprague-Dawley rats, respectively. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Plasma concentration-time profiles were explored by non-compartmental analysis. Visnagin plasma exposure (median AUClast and AUCinf) was significantly increased for all three doses (more than 10-fold for the low dose) when administered as an extract compared to the pure agent. For both the Ammi visnaga extract and the pure compound, AUClast and AUCinf increased disproportionately with an increase in dose. Visnagin resided significantly longer in the body when given in the form of AVE with up to a three times longer median MRTlast and MRTinf for the low dose. Cmax values after AVE administration were elevated and occurred at later time points in comparison to equivalent doses of pure visnagin. The terminal half-life increased with the dose for both AVE and pure visnagin, reaching a maximum value of 1.94 h for the 10 mg/kg pure compound group.In conclusion, the exposure of visnagin is enhanced after extract administration and could result in a superior efficacy of AVE compared to an equivalent dose of visnagin.

  20. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

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    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.

  1. Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration.

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    Geng, Ningbo; Zhang, Haijun; Xing, Liguo; Gao, Yuan; Zhang, Baoqin; Wang, Feidi; Ren, Xiaoqian; Chen, Jiping

    2016-02-01

    Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C10-, C11-, C12- and C13-CPs) after a single oral administration to the Sprague-Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with Cmax value of 2.3 mg L(-1). The half-lives of total SCCPs in blood for the absorption t1/2 (ka), distribution t1/2 (α) and elimination phases t1/2 (β) were calculated to be 1.0, 1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths.

  2. Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration.

    Science.gov (United States)

    Burka, L T; Black, S R; Mathews, J M

    1998-10-01

    1. The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

  3. Bioavailability and bioavailable forms of collagen after oral administration to rats.

    Science.gov (United States)

    Wang, Lin; Wang, Qing; Qian, Jing; Liang, Qiufang; Wang, Zhenbin; Xu, Junmin; He, Song; Ma, Haile

    2015-04-15

    The bioavailability and bioavailable forms of collagen after oral administration to rats were investigated in this study. The relative and absolute bioavailability of collagen were 57.8% and 49.6%, respectively, which was indirectly evaluated by the bioavailability of Hyp in collagen using a pharmacokinetic method. The amino acid profile of plasma showed that more than 63.4% of the collagen was absorbed from the intestine in the form of peptide, and there was a good linear correlation between the absorbed amount of an amino acid and its content in collagen (R(2) = 0.9225). The collagen peptides in plasma were purified by Sephadex G10 and Eclipse XDB C18 chromatography and further indentified (Ala-Asn, Ala-Hyp-Gly, Asp-Glu, Glu-Asn, Glu-Asp, Glu-Met, Gly-Pro-Hyp, Leu-Hyp, Leu-Met, Phe-Gly-Asn, Pro-Gly-Leu, Pro-Leu, Ser-Gly-Met, Ser-Hyp, Ser-Pro-Gly, Tyr-Met) with UPLC-ESI-MS. These results may help to speculate about the molecular mechanism behind the physiological effects of collagen after oral administration.

  4. Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

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    Tae Hwan Kim

    2014-01-01

    Full Text Available The potential pharmacokinetic (PK interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY and Achyranthes bidentata radix (AB extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW, OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42–4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (Cmax and longer time to reach Cmax (Tmax were observed in OY pretreated rats without changes in the area under the curve (AUC and the fraction excreted into urine (Furine. The absorption rate (Ka of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.

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

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    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.

  6. Terpenes transfer to milk and cheese after oral administration to sheep fed indoors.

    Science.gov (United States)

    Poulopoulou, I; Zoidis, E; Massouras, T; Hadjigeorgiou, I

    2012-04-01

    Terpenes have been proposed as potential biomarkers in verifying the diets of grazing animals. A study of the relationships between the intake of terpenes and their presence in animal tissues (blood and milk) as well as in the final product (cheese) was conducted. Eight dairy sheep were divided into two equal groups, representing control (C) and treatment group (T). In T group oral administration of a mixture of terpenes, α-pinene, limonene and β-caryophyllene, was applied over a period of 18 days. Blood and milk samples were collected regularly and terpenes were identified by extraction using petroleum ether and the solid phase micro-extraction (SPME) method, respectively, followed by GC-MS analysis. Cheese was produced, from C and T animals separately, twice during the period of terpenes oral administration. Terpenes contents and chemical properties of the produced cheeses were investigated. Limonene and α-pinene were found in all blood and milk samples of the T group after a lag-phase of 2 days, while β-caryophyllene was detected in few plasma samples and in all milk samples. None of the terpenes was traced in blood and milk of C animals. The contents of cheese, in dosed terpenes, presented a more complicated pattern suggesting terpenes non-credible as biomarkers. We conclude terpenes can be used as biomarkers for authentification of ewes' milk, but further research is required on factors affecting their transfer to dairy products from grazing diets.

  7. Pharmacokinetics of marbofloxacin, after one bolus oral administration in buffaloes calves: Preliminary study.

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    M.I. San Andrés

    2010-02-01

    Full Text Available Buffalo breeding system has a great economic importance in South-America, principally in marginal or sub-tropical lands. The therapeutic recommendations applied to a single ruminant species are extrapolated to others but important differences among those were recognized. Marbofloxacin bolus is indicated in the treatment of neonatal gastroenteritis caused by Escherichia coli, in calves (25-50kg. The aim of this study was determined the pharmacokinetic behaviour of marbofloxacin after oral administration, as bolus, following the label approved recommendations to cattle. One bolus (50 mg was administered in two clinically healthy buffaloes (two days-old, 48-50kg. Plasma concentrations of the marbofloxacin were determined by a HPLC/u.v. method. After oral administration, the values obtained were: tmax=0.5-6h, Cmax= 1.19-0.04μg/mL, AUCt=1.57-0.38μg·h/mL and MRTt= 3.34-6.92h, for calves 1 and 2 respectively. Fluoroquinolones act by concentration dependant killing mechanism, so high plasma concentration initially is important. For this reason, the recommended dose of 1mg/kg is inadequate in buffaloes.

  8. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  9. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.

  10. Effects of Withania somnifera on oral ethanol self-administration in rats.

    Science.gov (United States)

    Peana, Alessandra T; Muggironi, Giulia; Spina, Liliana; Rosas, Michela; Kasture, Sanjay B; Cotti, Elisabetta; Acquas, Elio

    2014-10-01

    Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited place conditioning. Here, we investigated the effect of W. somnifera roots extract (WSE) on motivation for drinking ethanol using operant self-administration paradigms. Wistar rats were trained to self-administer ethanol (10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on acquisition and maintenance, on ethanol breakpoint under a progressive-ratio schedule of reinforcement and on the deprivation effect and reinstatement of seeking behaviours. Moreover, on the basis of the recent suggestion of an involvement of GABAB receptors in WSE central effects, we studied the interaction between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self-administration was also tested. The results show that WSE reduced the acquisition, maintenance and breakpoint of ethanol self-administration. WSE also reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self-administration. These findings show that WSE, by an action that may involve GABAB receptors, impairs motivation for drinking ethanol and suggest that further investigations should be performed to determine whether W. somnifera may represent a new approach for the management of alcohol abuse.

  11. Solid lipid nanoparticles modified with stearic acid–octaarginine for oral administration of insulin

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    Zhang ZH

    2012-07-01

    Full Text Available Zhen-Hai Zhang,1,2 Yin-Long Zhang,2 Jian-Ping Zhou,2 Hui-Xia Lv21Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China; 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, ChinaAbstract: The aim of this study was to design and characterize solid lipid nanoparticles (SLNs modified with stearic acid–octaarginine (SA-R8 as carriers for oral administration of insulin (SA-R8-Ins-SLNs. The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R8-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA-R8. Morphological studies of SA-R8-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R8 could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R8-Ins-SLNs increased the Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R8-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R8-modified SLNs promote the oral absorption of insulin.Keywords: solid lipid nanoparticles, cell penetration peptides, stearic acid octaarginine, insulin, oral administration 

  12. Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

    Science.gov (United States)

    Date, Abhijit A; Nagarsenker, Mangal S; Patere, Shilpa; Dhawan, Vivek; Gude, R P; Hassan, P A; Aswal, V; Steiniger, Frank; Thamm, Jana; Fahr, Alfred

    2011-06-01

    The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

  13. Embryo-fetal exposure and developmental outcome of thalidomide following oral and intravaginal administration to pregnant rabbits.

    Science.gov (United States)

    Hui, Julia Y; Hoffmann, Matthew; Kumar, Gondi

    2014-09-01

    Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo-fetal development study using oral and intravaginal thalidomide administration at 2mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo-fetal developmental toxicity risks with thalidomide exposure via the vaginal route.

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

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    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.

  15. Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration.

    Science.gov (United States)

    Coetzee, J F; Mosher, R A; Griffith, G R; Gehring, R; Anderson, D E; KuKanich, B; Miesner, M

    2015-12-01

    The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration.

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

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    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.

  17. Influence of intravenous L-carnitine administration in sheep preceding an oral urea drench.

    Science.gov (United States)

    Chapa, A M; Fernandez, J M; White, T W; Bunting, L D; Gentry, L R; Ward, T L; Blum, S A

    1998-11-01

    Two experiments were conducted to investigate the effect of i.v. administration of L-carnitine on selected metabolites in sheep and to determine the feasibility of using L-carnitine to ameliorate the deleterious effects of hyperammonemia in sheep. In Exp. 1, i.v. L-carnitine solutions were administered at three levels in a replicated Latin square: 0 (CONT), 6.36 (CAR 1), and 12.72 (CAR 2) mmol L-carnitine/kg x (75) BW using Suffolk ewes (n = 6; average BW 75+/-3 kg). Plasma L-carnitine concentration was increased (P<.05) by treatment (51.9 vs 102.3, and 96.4 micromol/L in CONT, CAR 1, and CAR 2, respectively). Plasma glucose concentration was elevated (P<.05) in CAR 2 and CAR 1. Plasma NEFA concentration was highest (P<.05) in CAR 2. Area under the response curve for glucose was greater (P<.02) in CAR 2. In Exp. 2, Suffolk ewes (n = 16; average BW 48+/-2 kg) were used in a randomized complete block design with a 2x2 factorial treatment arrangement to determine the effects of i.v. L-carnitine administration during an oral urea load test (OULT). L-Carnitine (0 and 6.36 mmol/kg x (75) BW) was administered i.v. at 30 min, and an oral urea drench (50% wt/vol; 0 and 300 mg/kg BW) was administered at 60 min. Plasma L-carnitine was increased (P<.0001) by i.v. L-carnitine. Plasma ammonia N was highest (P<.0001) in the UREA treatment compared with the CONT, CARN, and CARN + UREA treatments (148 vs 95, 101, and 108 micromol/L, respectively). Intravenous L-carnitine administration influenced plasma glucose and NEFA concentrations in sheep and, when administered 30 min preceding an OULT, prevented the development of subclinical hyperammonemia in sheep.

  18. Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

    Science.gov (United States)

    Bianco, A W; Constable, P D; Cooper, B R; Taylor, S D

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses.

  19. [Patients' preferences for nurses' nonverbal expressions of warmth during nursing rounds and administration of oral medication].

    Science.gov (United States)

    Kim, H S; Kim, M S

    1990-12-01

    Nursing involves deep human interpersonal relationships between nurses and patients. But in modern Korea, the nurse-patient relationship tends to be ritualistic and mechanestic. Patients usually express the hope that nurses be more tender and kind. Patients expect nurses to express their warmth especially through nonverbal behaviour. This study was conducted to identify patients' preferences for nurse's nonverbal expressions of warmth. Through the confirmation of these preferences, nurses may learn how to enhance their interpersonal relationships with patients. Subjects for the study were 73 patients who had been admitted to a university teaching hospital for at least three days and agreed to be interviewed by the investigator. The interactions were studied nonverbal expressions of warmth during nursing rounds and administration of oral medication. The interview schedule was especially designed by the investigator to measure the nurse's posture, the distance between the nurse and the patient, the nurse's eye contact, facial expression, hand motion and head nodding. Data analysis included frequencies, percentages and X2-test. The results of this study may be summerized as follows: 1. Patient's preferences for nurse's nonverbal expressions of warmth during nursing rounds. Preferred nurse's posture was sitting (50.7%) or standing (49.3%) opposite the patient. Preferred distance between the nurse and the patient was close to the bed (93.2%), less than 1m. Preferred eye contact was directed to the patient's eyes or their affected part (41.1%). Preferred facial expression was a smile (97.3%). Preferred hand motions were light gestures (41.1%). Patients preferred head nodding which approved their own opinions (69.9%). 2. Patient's preferences for nurse's nonverbal expressions of warmth during administration of oral medication. Preferred nurse's posture was standing and waiting to confirm that the medication had been taken (58.9%). Preferred distance from the patient was

  20. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes.

    Directory of Open Access Journals (Sweden)

    Naoto Kudo

    Full Text Available Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT. Oxygen consumption (VO2 and energy expenditure (EE were increased significantly in mice treated with theaflavin rich fraction (TF compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes.

  1. Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.

    Science.gov (United States)

    Muñoz-Marín, Javier; De la Cruz, José Pedro; Reyes, José Julio; López-Villodres, Juan Antonio; Guerrero, Ana; López-Leiva, Inmaculada; Espartero, José Luis; Labajos, María Teresa; González-Correa, José Antonio

    2013-08-01

    The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT. Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats. Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B2 (TxB2), aortic 6-keto-prostaglandin F1α (6-keto-PGF1α) and nitrites+nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured. The administration of 20 mg/kg/day inhibited platelet aggregation, TxB2 and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative. Aortic nitrite and red blood cell GSH production were also increased. The aortic production of 6-keto-PGF1α was unaltered except in the group treated with the dodecyl derivative. The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect. In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease.

  2. Effects of Administration of Fostamatinib on Blood Concentrations of an Oral Contraceptive in Healthy Female Subjects

    Science.gov (United States)

    2012-02-17

    Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction; Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction

  3. 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

  4. Effect of Oral Administration of Enterococcus faecium Ef1 on Innate Immunity of Sucking Piglets

    Directory of Open Access Journals (Sweden)

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

    2013-01-01

    Full Text Available The objective of this study was to evaluate the effect of orally administered Enterococcus faecium EF1 on innate immune responses of jejunal mucosa in newborn piglets. Twenty-four commercial crossbred healthy newborn piglets were randomly divided into two groups, control (T0 and treatment (T1 group. Each group consists of 12 piglets. T1 was administered sterilized skim milk 2 ml piglet-1 day-1 with addition of E. faecium EF1 (5~6×108 cfu/ml by oral gavage on alternative odd days (1st, 3rd and 5th after birth. T0 fed with the same volume of sterilized skim milk without probiotics. The merciful killing of piglets at the 25th day after birth was performed to collect the samples of jejunal mucosa to measure the innate cytokine responses and the Toll-like receptors gene expression by quantitative real time PCR. The results showed that TGF-β1 and TNF-α concentrations increased and mRNA expression levels also improved significantly in T1 as compared to T0. While, the production of IFN-γ and IL-8 decreased significantly in T1 and gene expression modification was not observed. In addition, TLR (Toll-like receptor 2 and TLR 9 transcription levels were up-regulated in treatment (T1 group. These findings revealed that oral administration of E. faecium EF1 was effective to activate innate immunity and could modulate the TLRs expression in jejunal mucosa of piglets.

  5. Absorption of enrofloxacin and marbofloxacin after oral and subcutaneous administration in diseased koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Griffith, J E; Higgins, D P; Li, K M; Krockenberger, M B; Govendir, M

    2010-12-01

    Koalas (n = 43) were treated daily for up to 8 weeks with enrofloxacin: 10 mg/kg subcutaneously (s.c.), 5 mg/kg s.c., or 20 mg/kg per os (p.o.); or marbofloxacin: 1.0-3.3 mg/kg p.o., 10 mg/kg p.o. or 5 mg/kg s.c. Serial plasma drug concentrations were determined on day 1 and again at approximately 2 weeks, by liquid chromatography. The median (range) plasma maximum concentrations (C(max) ) for enrofloxacin 5 mg/kg s.c. and 10 mg/kg s.c. were 0.83 (0.68-1.52) and 2.08 (1.34-2.96) μg/mL and the median (range) T(max) were 1.5 h (1-2) and 1 h (1-2) respectively. Plasma concentrations of orally dosed marbofloxacin were too low to be quantified. Oral administration of enrofloxacin suggested absorption rate limited disposition pharmacokinetics; the median (range) C(max) for enrofloxacin 20 mg/kg p.o. was 0.94 (0.76-1.0) μg/mL and the median (range) T(max) was 4 h (2-8). Oral absorption of both drugs was poor. Plasma protein binding for enrofloxacin was 55.4 ± 1.9% and marbofloxacin 49.5 ± 5.3%. Elevations in creatinine kinase activity were associated with drug injections. Enrofloxacin and marbofloxacin administered at these dosage and routes are unlikely to inhibit the growth of chlamydial pathogens in vivo.

  6. 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.

  7. 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

    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 ... 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 2 days before severe trauma was induced with a stereotactic cryo-lesion. At 2 days post trauma, lesion size was determined. Brains were isolated...

  8. Eudragit EPO nanoparticles: application in improving therapeutic efficacy and reducing ulcerogenicity of meloxicam on oral administration.

    Science.gov (United States)

    Khachane, Parag; Date, Abhijit A; Nagarsenker, Mangal S

    2011-08-01

    The objective of this investigation was to evaluate the potential of Eudragit EPO nanoparticles (EPO NP) in improving therapeutic efficacy of meloxicam (MLX). MLX loaded EPO NP were prepared by nanoprecipitation method and were characterized for particle size, encapsulation efficiency and for morphology. The in vitro dissolution profile of MLX loaded EPO NP and MLX suspension was evaluated. MLX loaded EPO NP had particle size of approximately 100 nm and the encapsulation efficiency of MLX was approximately 90%. The EPO NP significantly improved anti-inflammatory activity of MLX (P EPO NP Oral administration of MLX loaded EPO NP also resulted in lesser ulcerogenicity as compared to that of MLX suspension indicating that nanoparticles can also decrease the adverse effects associated with MLX treatment.

  9. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    Science.gov (United States)

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  10. Oral administration of Brazilian propolis exerts estrogenic effect in ovariectomized rats.

    Science.gov (United States)

    Okamoto, Yoshinori; Tobe, Takao; Ueda, Koji; Takada, Tatsuyuki; Kojima, Nakao

    2015-04-01

    Propolis, a natural product derived from plants by honeybees, is a mixture of several hundred chemicals, including flavonoids, coumaric acids, and caffeic acids, some of which show estrogen-like activity. In this study, the estrogenic activity of crude ethanolic extract of Brazilian propolis was determined using several in vitro and in vivo assays. Propolis was found to bind to human estrogen receptors (ERs). Furthermore, propolis induced the expression of estrogen-responsive genes in ER-positive MCF-7 and Ishikawa cells. These in vitro assays suggest that propolis exerts estrogenic activity; therefore, in vivo experiments were conducted using ovariectomized rats. Oral administration of propolis (55 or 550 mg/kg/day for 3 days) significantly increased uterine wet weight and luminal epithelium thickness in comparison with the corresponding values in the corn oil-treated control group. Moreover, propolis induced ductal cell proliferation in the mammary glands. These effects were completely inhibited by full ER antagonist ICI 182,780, confirming that the effects of propolis are mediated by the ER. Our data show that oral intake of propolis induces estrogenic activity in ER-expressing organs in vivo and suggest that Brazilian propolis is a useful dietary source of phytoestrogens and a promising treatment for postmenopausal symptoms.

  11. Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes

    Directory of Open Access Journals (Sweden)

    Shuaishuai Wang

    2017-01-01

    Full Text Available Purpose. This study was performed to measure the concentration of trans-resveratrol and its three metabolites in human eyes. Methods. The patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment were included. The participants were orally given trans-resveratrol-based supplement (Longevinex®. A suitable amount of conjunctiva, aqueous humor, and vitreous humor were obtained during the operation. High-performance liquid chromatography (HPLC with mass spectrometry (LC/MS/MS was used to detect the concentration of trans-resveratrol and its three metabolites in the various samples. Results. The average concentration of resveratrol in the conjunctiva was 17.19 ± 15.32 nmol/g (mean ± SD. The concentration of resveratrol in the aqueous humor was close to the limit of detection, but its metabolites could be quantified. The concentrations of resveratrol metabolites in the aqueous humor can be detected. In the vitreous humor, the average concentration of resveratrol-3-O-sulfate was 62.95 ± 41.97 nmol/L. The sulfate conjugations of resveratrol were recovered in the conjunctiva, aqueous humor, and vitreous humor. Conclusions. Resveratrol and its three metabolites can be detected in the ocular tissues after oral administration. Although the concentration of parent resveratrol was low in the eyes, its metabolites could be detected and may have a role in the treatment of ocular diseases.

  12. Pharmacokinetic profiles of meloxicam in turtles (Trachemys scripta scripta) after single oral, intracoelomic and intramuscular administrations.

    Science.gov (United States)

    Di Salvo, A; Giorgi, M; Catanzaro, A; Deli, G; della Rocca, G

    2016-02-01

    Meloxicam is an anti-inflammatory and analgesic drug used to treat many pathological conditions in turtles. With the aim to fill the lack of data about its pharmacokinetic in this species, eighteen turtles (Trachemys scripta scripta) were divided in three groups and treated with a single dose of meloxicam (0.2 mg/kg) by intramuscular, intracoelomic and oral route, respectively. At scheduled time points, blood samples were collected and meloxicam concentrations were determined by HPLC. Pharmacokinetic parameters were calculated from the obtained concentration-time curves. After intramuscular treatment, a plasma peak of meloxicam equal to 1590.03 ± 1845.32 ng/mL (mean ± SD) and a Tmax of 1.17 ± 0.45 h were reached, indicating a quick absorption of the drug. The intracoelomic administration brought to the largest AUC (12621.04 ± 6203.79 h*ng/mL) and to a Cmax and a Tmax equal to 1154.52 ± 662.78 ng/mL and 2.82 ± 1.39 h, respectively. Following oral treatment, the plasma concentrations of meloxicam were very low indicating a scarce absorption. Further studies are warranted to determine the effective plasma concentration of meloxicam in turtles and, consequently, the dosage regimen.

  13. Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes

    Science.gov (United States)

    Li, Ying; Zhu, Chunyan

    2017-01-01

    In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine–polyethylene glycol–cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells.

  14. Polyelectrolyte complex of carboxymethyl starch and chitosan as protein carrier: oral administration of ovalbumin.

    Science.gov (United States)

    Assaad, Elias; Blemur, Lindsay; Lessard, Martin; Mateescu, Mircea Alexandru

    2012-01-01

    A novel carboxymethyl starch (CMS)/chitosan polyelectrolyte complex (PEC) was proposed as an excipient for oral administration of ovalbumin. The dissolution of ovalbumin from monolithic tablets (200 mg, 2.1 × 9.6 mm, 50% loading) obtained by direct compression was studied. When CMS was used as an excipient, more than 70% of the loaded ovalbumin remained undigested after 1 h of incubation in simulated gastric fluid (SGF) with pepsin. The complete dissolution, after transfer of tablets into simulated intestinal fluid (SIF) with pancreatin, occurred within a total time of about 6 h. Higher protection (more than 90% stability in SGF) and longer dissolution (more than 13 h) were obtained with 50% CMS/50% chitosan physical mixture or with PEC excipients. A lower proportion of chitosan was needed for PEC than for the CMS/chitosan mixture to obtain a similar dissolution profile. The high protection against digestion by pepsin, the various release times and the mucoadhesion properties of these excipients based on CMS favor the development of suitable carriers for oral vaccinations.

  15. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats

    Directory of Open Access Journals (Sweden)

    Junke Song

    2015-05-01

    Full Text Available A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI source. A single ion monitoring scanning (SIM mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%−104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C2min were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (Cmax was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0−t was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg and oral administration (4 mg/kg, respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.

  16. [Relative bioavailability of glucosamine after oral, intramuscular and transdermal administration of hondroxid maximum preparation in experiment].

    Science.gov (United States)

    Yasso, B; Li, Y; Alexander, A; Mel'nikova, N B; Mukhina, I V

    2014-01-01

    A comparison of the relative bioavailability and intensity of penetration of glucosamine sulfate in oral, injection and topical administration of the dosage form Hondroxid Maximum as a cream containing micellar system for transdermal delivery of glucosamine in the experiment by Sprague-Dawley rats was carried out. On the base on the pharmacokinetic profiles data of glucosamine in rat blood plasma with daily administration in 3 times a day for 1 week by cream Hondroxid Maximum 400 mg/kg and the single injection solution of 4% Glucosamine sulfate 400 mg/kg was found that the relative bioavailability was 61.6%. Calculated penetration rate of glucosamine in the plasma through the rats skin in 4 hours, equal to 26.9 μg/cm2 x h, and the penetration of glucosamine through the skin into the plasma after a single dose of cream in 4 hours was 4.12%. Comparative analysis of literature and experimental data and calculations based on them suggest that medicine Hondroxid Maximum, cream with transdermal glucosamine complex in the treatment in accordance with the instructions can provide an average concentration of glucosamine in the synovial fluid of an inflamed joint in the range (0.7 - 1.5) μg/ml, much higher than the concentration of endogenous glucosamine human synovial joint fluid (0.02 - 0.07 μg/ml). By theoretical calculations taking into account experimental data it is shown that the medicine Hondroxid Maximum can reach the bioavailability level of the modern injection forms and exceed the bioavailability level of modern oral forms of glucosamine up to 2 times.

  17. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

    Directory of Open Access Journals (Sweden)

    Andrew Osayame Eweka

    2010-01-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers′ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

  18. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats.

    Science.gov (United States)

    Song, Junke; Zhang, Wen; Sun, Jialin; Xu, Xiaona; Zhang, Xue; Zhang, Li; Feng, Zhangying; Du, Guan-Hua

    2015-05-01

    A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C 2min) were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (C max) was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0-t ) was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.

  19. Immunomodulatory consequences of oral administration of Lactobacillus rhamnosus strain GG in healthy volunteers.

    Science.gov (United States)

    Schultz, Michael; Linde, Hans-Jörg; Lehn, Norbert; Zimmermann, Kurt; Grossmann, Johannes; Falk, Werner; Schölmerich, Jürgen

    2003-05-01

    Probiotic microorganisms, especially lactic acid bacteria, are effective in the treatment of infectious diarrhoeal diseases and experimental colitis. Although the mechanisms by which these organisms exert their anti-inflammatory effects are largely unknown, immunomodulating effects are suggested. The objective of this study was to examine the effect of a 5-week oral administration of Lactobacillus rhamnosus subspecies GG (Lb. GG) on the cellular immune response to intestinal microorganisms in ten healthy volunteers. Peripheral blood cells (PB) were stimulated with either 'self' or 'non-self' preparations of faecal samples and isolated Bacteroides fragilis group-organisms (Bfg) or Escherichia coli (Esch. coli), and pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-gamma, TNF-alpha) were measured in the culture supernatant. CD4+ T-lymphocyte activation was determined by measurement of intracellular ATP following lysis of the cells. The activational response of CD4+ T-lymphocytes towards isolated and heat-inactivated intestinal organisms was increased after the probiotic treatment. Additionally, TNF-alpha, IL-6 and in part IFN-gamma cytokine secretion by PB cells following stimulation with whole stool preparations and single members of the flora was significantly decreased, whereas the IL-10 and in part IL-4 cytokine secretion was increased at the end of the study. In contrast, the activational response of CD4+ T-lymphocytes following stimulation with whole 'non-self' intestinal flora was higher than by 'self' intestinal flora, but both responses showed a trend towards a reduction at the end of the study. This study documents a direct effect by Lb. GG on the cellular immune system of healthy volunteers and offers a promising tool to investigate systemic immunomodulation due to oral administration of probiotic microorganisms.

  20. Histological effects of oral administration of nutmeg on the kidneys of adult Wister rats

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    Andrew Osayame Eweka

    2010-04-01

    Full Text Available Aims: The effects of oral administration of nutmeg commonly used as spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the kidneys of adult Wistar rats were carefully studied. Material and Methods: Rats of both sexes (n = 24, with average weight of 220g were randomly assigned into two treatments (A & B of (n=16 and Control (c (n=8 groups. The rats in the treatment groups (A & B received 0.1g (500mg/kg body weight and 0.2g (1000mg/kg body weight of nutmeg thoroughly mixed with the feeds respectively on a daily basis for forty-two days. The control group (c received equal amount of feeds daily without nutmeg added for forty-two days. The growers’ mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state, Nigeria and the rats were given water liberally. The rats were sacrificed by cervical dislocation on the forty-third day of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% buffered formaldehyde for routine histological study after hematoxylin and eosin method. Result: The histological findings in the treated sections of the kidneys showed distortion of the renal cortical structures, vacuolations appearing in the stroma and some degree of cellular necrosis, with degenerative and atrophic changes when compared to the control group. Conclusion: These findings indicate that oral administration of nutmeg may have some deleterious effects on the kidneys of adult Wistar rats at higher doses and by extension may affect its excretory and other metabolic functions. It is recommended that caution should therefore be advocated in the intake of this product and further studies be carried out to examine these findings.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    AIM: 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.METHODS: 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 CⅡ 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.RESULTS: 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 μg/kg)could suppress the secondary hind paw swelling(P<0.05for 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 μg/kg) showed the limited efficacy on arthritis

  2. Oral administration of an immunostimulatory DNA sequence from Bifidobacterium longum improves Th1/Th2 balance in a murine model.

    Science.gov (United States)

    Takahashi, Noritoshi; Kitazawa, Haruki; Iwabuchi, Noriyuki; Xiao, Jin-Zhong; Miyaji, Kazuhiro; Iwatsuki, Keiji; Saito, Tadao

    2006-08-01

    We have reported the antiallergic activities of the immunostimulatory oligodeoxynucleotide (ODN) BL07S, identified from genomic DNA of Bifidobacterium longum BB536 from in vitro and in vivo studies. The present study evaluated the efficiency of ODN BL07S in preventing allergic responses by oral administration. Oral administration of BL07S suppressed serum ovalbumin (OVA)-specific immunoglobulin (Ig) E levels and improved the OVA-specific IgG2a/IgG1 ratio. ODN BL07S increased Th1 cytokine and decreased Th2 cytokine production in splenocytes. These results suggest that immunostimulatory ODNs are potentially associated with the antiallergic effects of probiotics.

  3. Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides on renovascular hypertension.

    Science.gov (United States)

    Zhuang, Yongliang; Sun, Liping; Zhang, Yufeng; Liu, Gaoxiang

    2012-02-01

    Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides (JCP) on renovascular hypertension rats (RVHs) was evaluated. The systolic blood pressure and diastolic blood pressure of the RVHs were significantly reduced with administration of JCP (p oral treatment with high dose JCP (p > 0.05). Furthermore, effect of JCP on angiotensin II (Ang II) concentration of plasma had no significance (p > 0.05), but JCP significantly inhibited the Ang II concentration in RVHs' kidney (p < 0.05). The kidney should be the target site of JCP.

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

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    C. GAVAN

    2013-07-01

    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.

  6. Changes in urinary metabolic profile after oral administration of curcuma extract in rats.

    Science.gov (United States)

    Dall'Acqua, Stefano; Stocchero, Matteo; Clauser, Maria; Boschiero, Irene; Ndoum, Emmanuel; Schiavon, Mariano; Mammi, Stefano; Schievano, Elisabetta

    2014-11-01

    The diffusion of phytochemicals in health promoting products is growing, but studies related to their effects on healthy subjects are still lacking despite the large consumption of natural products as nutraceuticals or food supplements. In many cases, research supports the in vitro antioxidant activity of phytochemicals, but the health claims attributed to the final marketed nutraceutical products have dubious scientific foundation. Also, studies focussed on the definition of their biological targets and mechanisms of action can be useful to assess their efficacy and safety. In this study, the effect of oral administration of 80mg/kg of Curcuma longa Linn. extract to 12 healthy rats over 25 days was evaluated by monitoring the changes of urinary composition. 24-h urine was collected during the animal experiment and the composition was analyzed by (1)H NMR and HPLC-MS. The two datasets were studied individually through a metabolomic approach and the multivariate analysis revealed significant differences between the control and the treated group. Curcumin levels were also measured in 24-h urine samples by HPLC-MS. Both the (1)H NMR and the HPLC-MS dataset showed that the administration of 80mg/kg of Curcuma longa extract to healthy animals induces changes in urinary composition. Decreased allantoin urinary levels can be considered a partial demonstration of the in vivo effect of curcumin on oxidative stress in a healthy animal model.

  7. No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats.

    Science.gov (United States)

    Suzuki, Masaaki; Yamazaki, Kazunori; Kano, Hirokazu; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji

    2012-01-01

    The carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined by oral administration using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats were given drinking water containing ETBE at doses of 0, 625, 2,500 or 10,000 ppm (w/w) for 104 weeks. No significant increase in the incidence of tumors was detected in any organ of either sex. Rat-specific non-neoplastic lesions were observed in the kidney: An increase in the severity of chronic progressive nephropathy was observed in the male and female 10,000 ppm groups, and increased incidences of urothelial hyperplasia of the pelvis and mineral deposition in the renal papilla were observed in the male 2,500 and 10,000 ppm groups. Besides these lesions, no treatment-related histopathological changes were observed in any organ or tissue in either sex. Thus, the present study demonstrated that a two year administration ETBE in the drinking water did not exert any carcinogenic effects in either male or female rats.

  8. Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

    Science.gov (United States)

    Li, Renjun; Ma, Yanfen; Zhai, Lijuan; Lu, Yisong; Chi, Xiaoqing; Wu, Jiusheng; Hu, Songhua

    2016-08-01

    Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals.

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

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    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.

  10. Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

    Science.gov (United States)

    Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

    2016-08-01

    The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

  11. 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.

  12. 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 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.

  13. Evaluation of hepatic glucose metabolism via gluconeogenesis and glycogenolysis after oral administration of insulin nanoparticles.

    Science.gov (United States)

    Woitiski, Camile B; Neufeld, Ronald J; Soares, Ana F; Figueiredo, Isabel V; Veiga, Francisco J; Carvalho, Rui A

    2012-12-01

    Nanoparticles were designed to promote insulin intestinal absorption via the oral route, to increase portal insulin levels to better mimic the physiological pathway, providing enhanced glucose control through glycogenolysis and gluconeogenesis. Nanoparticles were formulated with insulin encapsulated in the core material consisting of alginate and dextran sulfate, associated with poloxamer and subsequently coated with chitosan then albumin. A spherical and slightly rough core was observed in electron micrographs with the appearance of a concentration gradient of the polysaccharide structure toward the periphery of the nanoparticle. Atomic force microscopy showed that the fully formed nanoparticles are about 200 nm in diameter with smooth and spherical morphology. Histopathological analysis of organs and tissues of diabetic rats dosed daily for 15 days with insulin nanoparticles was used to evaluate toxicological issues. No morphological or pathological alterations were observed in rat liver, spleen, pancreas, kidney or intestinal sections. Following, the effect of nanoencapsulated insulin on inhibiting hepatic gluconeogenesis was evaluated after a single insulin administration and oral glucose tolerance test, which represents a significant metabolic challenge to the liver. Alterations in the hepatic glucose metabolism of fasted streptozotocin-diabetic rats were determined by the percent contribution of glycogenolysis and gluconeogenesis, measured by using metabolic tracers, however similar gluconeogenesis contribution to the hepatic metabolism was observed between diabetic rats receiving nanoencapsulated insulin or insulin solution. The metabolic results may be explained by the inability of a single dose in shifting the gluconeogenesis/glycogenolysis contributions, sampling time, fasting period or by influence of the kidney enzymes and impairment in insulin signaling observed in stz-diabetic rats.

  14. Synthesis and profiling of [3H]trantinterol excretion following oral administration of rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tian-hong; ZHANG Cheng; YANG Cui-ping; WANG Xiao-ying; LIAO Sha; SUN Mu-zhen; LI Jing-lai; ZHANG Zhen-qing

    2015-01-01

    OBJECTIVE To synthesize[3H]labelled trantinterol and determine the mass balance in rats and the profile of trantinterol and its metabolites in excreta. METHODS [3H]Trantinterol was synthesised from the intermediate1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-bromo-ethanone through reduction by sodium borotritide and aminolysis by t-butylamine. Following an oral dose of[3H] trantinterol(45.5 MBq·kg-1)to bile duct cannulated(BDC)rats and normal rats. Bile,urine and faeces were collected individually before and after dosing at different times. Liquid scintillation counter(LSC) was used to detect total radioactivity recovery and HPLC/radio-detector for metabolite profiling in urine and bile. RESULTS The majority(73.6%)of the administered radioactivity was recovered in the first 24 h postdose with 48.3%in urine and 25.4%in faeces. It was cumulated to(84.7±6.8)%till 168 h. In BDC rats,29.3%of the dose was recovered in the bile 3 d post-dose. According to the peak area ratio determined by HPLC/radio-detector,only 4.7%and 9.5%of the radioactive dose were excreted as the parent drug in urine and bile,respectively,while the majority of the remaining radioactivity was excreted in the form of various metabolites. CONCLUSION Following oral administration in rats,trantinterol is completely absorbed,extensively metabolized and rapidly excreted mainly in urine as various metabolites.

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

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    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.

  16. 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.

  17. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

    Directory of Open Access Journals (Sweden)

    Shin Chang-Sik

    2011-09-01

    Full Text Available Abstract Artesunate (AS is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA. In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV, intramuscular (IM, oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%. Similarly high bioavailability of DHA (> 80% is associated with oral administration. Following oral AS, peak AS concentrations (Cmax are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS

  18. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration.

    Science.gov (United States)

    Morris, Carrie A; Duparc, Stephan; Borghini-Fuhrer, Isabelle; Jung, Donald; Shin, Chang-Sik; Fleckenstein, Lawrence

    2011-09-13

    Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not

  19. 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...

  20. Effect of castration timing and oral meloxicam administration on growth performance, inflammation, behavior and carcass quality of beef calves

    Science.gov (United States)

    Beef bull calves (n = 62) were assigned randomly, within sire breed, to 1 of 4 treatments at birth. Treatments were: 1) surgical castration near birth, 2) surgical castration near birth with oral administration of meloxicam (1 milligram/kilogram of body weight), 3) surgical castration at weaning (WN...

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

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    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.

  2. DNA damage detected by the alkaline comet assay in the liver of mice after oral administration of tetrachloroethylene

    DEFF Research Database (Denmark)

    Cederberg, H.; Henriksson, J.; Binderup, Mona-Lise

    2010-01-01

    Induction of DNA damage in the liver and kidney of male CD1 mice was studied by means of the alkaline Comet assay after oral administration of tetrachloroethylene at the doses of 1000 and 2000 mg/kg/day. A statistically significant dose-related increase in tail intensity was established...

  3. Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent

    Science.gov (United States)

    AFUWAPE, A O; TURNER, M W; STROBEL, S

    2004-01-01

    Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (β-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-β was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory

  4. Does switching from oral to subcutaneous administration of methotrexate influence on patient reported gastro-intestinal adverse effects?

    DEFF Research Database (Denmark)

    Kromann, Charles B; Lage-Hansen, Philip R; Koefoed, Mette

    2015-01-01

    INTRODUCTION: When treating patients with methotrexate (MTX) the most frequently reported adverse effects (AE) are gastrointestinal (GI) with nausea being reported by 10-20%. If intolerable AE of oral MTX persist, switching from oral to subcutaneous (SC) or intramuscular (IM) administration...... is common. However, this approach is largely empirical and the evidence is inconsistent. To our knowledge, this will be the first study to estimate the change in GI AE of switching from oral to SC MTX. METHODS: A retrospective postal survey was sent to patients who had changed from oral MTX to SC MTX. GI AE...... was rated by visual analogue scale (VAS) regarding frequency and intensity of nausea, frequency of vomiting and frequency of discomfort. All participants gave informed consent. No further ethical clearance was necessary according to national law. RESULTS: Of the sample 39/57 (68.4%) responded. Significant...

  5. Population pharmacokinetics of a single dose of meloxicam after oral and intramuscular administration to captive lesser flamingos (Phoeniconaias minor).

    Science.gov (United States)

    Zordan, Martín A; Papich, Mark G; Pich, Ashley A; Unger, Katy M; Sánchez, Carlos R

    2016-12-01

    OBJECTIVE To determine the pharmacokinetics of a single dose of meloxicam after IM and oral administration to healthy lesser flamingos (Phoeniconaias minor) by use of a population approach. ANIMALS 16 healthy captive lesser flamingos between 1 and 4 years of age. PROCEDURES A single dose of meloxicam (0.5 mg/kg) was administered IM to each bird, and blood samples were collected from birds at 3 (n = 13 birds), 2 (2), or 1 (1) selected point between 0 and 13 hours after administration, with samples collected from birds at each point. After a 15-day washout period, the same dose of meloxicam was administered PO via a red rubber tube and blood samples were collected as described for IM administration. Pharmacokinetic values were determined from plasma concentrations measured by high-performance liquid chromatography. RESULTS Plasma drug concentrations after IM administration of meloxicam reached a mean ± SD maximum value of 6.01 ± 3.38 μg/mL. Mean area under the concentration-versus-time curve was 17.78 ± 2.79 μg•h/mL, and mean elimination half-life was 1.93 ± 0.32 hours. Plasma concentrations after oral administration reached a mean maximum value of 1.79 ± 0.33 μg/mL. Mean area under the curve was 22.16 ± 7.17 μg•h/mL, and mean elimination half-life was 6.05 ± 3.53 hours. CONCLUSIONS AND CLINICAL RELEVANCE In lesser flamingos, oral administration of meloxicam resulted in higher bioavailability and a longer elimination half-life than did IM administration, but the maximum plasma concentration was low and may be insufficient to provide analgesia in flamingos. Conversely, IM administration achieved the desired plasma concentration but would require more frequent administration.

  6. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

    Science.gov (United States)

    Kukulka, Michael; Nudurupati, Sai; Perez, Maria Claudia

    2017-01-01

    Background Dexlansoprazole is a proton pump inhibitor (PPI) approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT) formulations. Aim To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG) tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results Equivalent values for area under the plasma concentration–time curve (AUC) were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax) was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water) was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3%) and were 12% higher in the fed state than in the fasted state. Conclusion The AUC from the dexlansoprazole ODT was equivalent when administered in the fed and fasted states. Equivalent systemic exposure to

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

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    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.

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

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    Temitayo O. Iji

    2013-02-01

    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.

  9. Polyphenol extract from evening primrose pomace alleviates experimental colitis after intracolonic and oral administration in mice.

    Science.gov (United States)

    Sałaga, M; Lewandowska, U; Sosnowska, D; Zakrzewski, P K; Cygankiewicz, A I; Piechota-Polańczyk, A; Sobczak, M; Mosinska, P; Chen, Chunqiu; Krajewska, W M; Fichna, J

    2014-11-01

    Oenothera paradoxa (EP) preparations are commonly used in folk medicine to treat skin diseases, neuralgia, and gastrointestinal (GI) disorders. Several reports suggested that EP preparations exhibit potent anti-inflammatory and antioxidant activities both in vitro and in vivo. Here, we aimed to characterize the action of EP pomace polyphenol extract in mouse model of colitis. We analyzed the composition of EP pomace polyphenol extract using reversed phase HPLC system and ultra-performance liquid chromatography (UPLC) system coupled with a quadrupole-time of flight (Q-TOF) MS instrument. Then, we used a well-established animal model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis to determine the anti-inflammatory action of EP pomace polyphenol extract. We also investigated the effect of the EP pomace polyphenol extract on pro-inflammatory (IL-1β and TNF-α) cytokine mRNA levels and hydrogen peroxide concentration in the inflamed colon. Administration of EP pomace polyphenol extract significantly improved macroscopic and microscopic damage scores, as well as myeloperoxidase (MPO) activity in TNBS-treated mice. The anti-inflammatory effect of the extract was observed after intracolonic and oral administration and was dose-dependent. Significant reduction of tissue hydrogen peroxide level after treatment with EP pomace polyphenol extract suggests that its therapeutic effect is a result of free radical scavenging. This novel finding indicates that the application of the EP pomace polyphenol extract in patients with inflammatory bowel diseases (IBDs) may become an attractive supplementary treatment for conventional anti-inflammatory therapy.

  10. Comparative bioavailability study of two ibuprofen preparations after oral administration in healthy volunteers.

    Science.gov (United States)

    Bienert, Agnieszka; Szkutnik-Fiedler, Danuta; Dyderski, Stanisław; Grześkowiak, Edmund; Drobnik, Leon; Wolc, Anna; Slawińiska, Urszula

    2006-01-01

    The bioavailability of a new ibuprofen (2-(p-isobutylphenyl)propionic acid, CAS 15687-27-1) preparation was compared with a reference preparation of the drug in 23 healthy male volunteers, aged between 19 and 27. A single dose of 400 mg was given orally in the fasted state, using a randomized two-way crossover study. A washout period of two weeks separated both treatment periods. Ibuprofen plasma levels were determined by means of a validated HPLC method (UV detector). Values of 154.48 +/- 53.27 microg x h/ml (95 % confidence interval CI: 133.50-177.03) for the test, and 140.86 +/- 44.82 microg x h/ml (95% CI: 122.53-159.16) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum plasma concentrations Cmax of 39.53 +/- 7.11 microg/ml (95 % CI: 35.97-41.78) and 37.71 +/- 8.67 microg/ml (95% CI: 33.37-40.46) achieved for the test and reference preparations did not differ significantly. AUC(0-infinity) and Cmax ratios (90% CI) were within the 80-125% interval required for bioequivalence as stipulated in the current international regulations of the European Agency for the Evalution of Medicinal Products and the Food and Drug Administration. Therefore it is concluded that the new ibuprofen preparation is therapeutically equivalent to the reference preparation for both, the extent and the rate of absorption, after single dose administration in healthy volunteers.

  11. 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.

  12. Oral administration of putrescine and proline during the suckling period improves epithelial restitution after early weaning in piglets.

    Science.gov (United States)

    Wang, J; Li, G R; Tan, B E; Xiong, X; Kong, X F; Xiao, D F; Xu, L W; Wu, M M; Huang, B; Kim, S W; Yin, Y L

    2015-04-01

    Polyamines are necessary for normal integrity and the restitution after injury of the gastrointestinal epithelium. The objective of this study was to investigate the effects of oral administration of putrescine and proline during the suckling period on epithelial restitution after early weaning in piglets. Eighteen neonatal piglets (Duroc × Landrace × Large Yorkshire) from 3 litters (6 piglets per litter) were assigned to 3 groups, representing oral administration with an equal volume of saline (control), putrescine (5 mg/kg BW), and proline (25 mg/kg BW) twice daily from d 1 to weaning at 14 d of age. Plasma and intestinal samples were obtained 3 d after weaning. The results showed that oral administration of putrescine or proline increased the final BW and ADG of piglets compared with the control (P putrescine- and proline-treated piglets compared with those of control piglets. The voltage-gated K+ channel (Kv) 1.1 protein expression in the jejunum of piglets administrated with putrescine and the Kv1.5 mRNA and Kv1.1 protein levels in the ileum of piglets administrated with proline were greater than those in control piglets (P < 0.05). These findings indicate that polyamine or its precursor could improve mucosal proliferation, intestinal morphology, as well as tight junction and potassium channel protein expressions in early-weaned piglets, with implications for epithelial restitution and barrier function after stress injury.

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

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    Susanne W. Bruun

    2016-01-01

    Full Text Available Gluten promotes type 1 diabetes in nonobese diabetic (NOD mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin 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 and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes.

  14. Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid.

    Science.gov (United States)

    Sun, Jiarui; Zhang, Xinchen; Cao, Yinan; Zhao, Qiling; Bao, Endong; Lv, Yingjun

    2016-01-01

    Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.

  15. Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral Administration.

    Science.gov (United States)

    Box, Karl J; Comer, John; Taylor, Robert; Karki, Shyam; Ruiz, Rebeca; Price, Robert; Fotaki, Nikoletta

    2016-04-01

    The purpose of this study was to better understand the dissolution properties and precipitation behavior of pharmaceutical cocrystals of poorly soluble drugs for the potential for oral administration based on a small-scale dissolution assay. Carbamazepine and indomethacin cocrystals with saccharin and nicotinamide as coformers were prepared with the sonic slurry method. Dissolution of the poorly soluble drugs indomethacin and carbamazepine and their cocrystals was studied with a small-scale dissolution assay installed on a SiriusT3 instrument. Two methodologies were used: (i) surface dissolution of pressed tablet (3 mm) in 20 mL running for fixed times at four pH stages (pH 1.8, pH 3.9, pH 5.4, pH 7.3) and (ii) powder dissolution (2.6 mg) in 2 mL at a constant pH (pH 2). Improved dissolution and useful insights into precipitation kinetics of poorly soluble compounds from the cocrystal form can be revealed by the small-scale dissolution assay. A clear difference in dissolution/precipitation behaviour can be observed based on the characteristics of the coformer used.

  16. Application properties of oral gels as media for administration of minitablets and pellets to paediatric patients.

    Science.gov (United States)

    Kluk, Anna; Sznitowska, Malgorzata

    2014-01-02

    Modern solid multiparticulate drug forms (minitablets, pellets, granules) can provide the possibility of precise dosing or modified drug release or taste masking for medicines used in children. However, these solid particles require an adequate medium to ease swallowing. The aim of the research was to design a universal semisolid dispersing medium for administration of minitablets and pellets. High viscosity sodium carmellose and carbomer were considered as gelling agents. The hydrogels were prepared with sucrose, glycerol, and potassium sorbate or parabens. Preliminary studies were undertaken to estimate the application properties of the gels under conditions where a medicine is administered to a child. Besides standard tests (viscosity, sedimentation) the following measurements were conducted: gel ductility, mass of the gel removed from a spoon under shaking, ability of the gels to disperse solid particles, and disintegration of minitablets in the gels. The oral hydrogels prepared either with 1.0% and 1.5% carmellose or 0.25% and 0.5% (w/w) carbomer were suitable for dispersing and delivery of minitablets or pellets. Not only viscosity but also ductility was an essential criterion in selecting the best vehicle. The in vivo perceptibility test for pellets and minitablets did not confirm that gels are more advantageous than syrups.

  17. The prevalence of trimetazidine use in athletes in Poland: excretion study after oral drug administration.

    Science.gov (United States)

    Jarek, Anna; Wójtowicz, Marzena; Kwiatkowska, Dorota; Kita, Monika; Turek-Lepa, Ewa; Chajewska, Katarzyna; Lewandowska-Pachecka, Sylwia; Pokrywka, Andrzej

    2014-01-01

    Stimulants, together with anabolic androgenic steroids, are regarded as one of the most popular doping substances in sport. Owing to a great variety of these substances and new designer drugs being introduced to the market, each year the World Anti-Doping Agency (WADA) updates the list of substances and methods prohibited in sport. On 1 January 2014, a new doping agent - trimetazidine (TMZ) - was added to the WADA Prohibited List. TMZ, a substance prohibited in competition, is classified in the S6b Specified Stimulant Group. TMZ is used as a well-known cardiologic drug with confirmed biochemical and clinical activity. According to knowledge of the pharmacology and mechanism of TMZ action, TMZ can be used by athletes to improve physical efficiency, especially in the case of endurance sports. This study presents the phenomena of TMZ use by Polish athletes involved in anti-doping control in the WADA-accredited laboratory in Warsaw (Poland) between 2008 and 2013. Samples were taken from the athletes of such disciplines as cycling, athletics, and triathlon. Moreover, the elimination study of TMZ has been conducted to establish the change of TMZ concentration in urine sample after oral administration of a single or double (during the long-term therapy) dose. TMZ was monitored in urine samples by gas chromatography-mass spectrometry-nitrogen phosphorus detection (GC-MS-NPD).

  18. Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man.

    Science.gov (United States)

    Hasler, Felix; Bourquin, Daniel; Brenneisen, Rudolf; Vollenweider, Franz X

    2002-09-01

    In a clinical study eight volunteers received psilocybin (PY) in psychoactive oral doses of 212+/-25 microg/kg body weight. To investigate the elimination kinetics of psilocin (PI), the first metabolite of PY, urine was collected for 24 h and PI concentrations were determined by high-performance liquid chromatography with column switching and electrochemical detection (HPLC-ECD). Sample workup included protection of the unstable PI with ascorbic acid, freeze-drying, and extraction with methanol. Peak PI concentrations up to 870 microg/l were measured in urine samples from the 2-4 h collection interval. The PI excretion rate in this period was 55.5+/-33.8 microg/h. The limit of quantitation (10 microg/L) was usually reached 24 h after drug administration. Within 24 h, 3.4+/-0.9% of the applied dose of PY was excreted as free PI. Addition of beta-glucuronidase to urine samples and incubation for 5 h at 40 degrees C led to twofold higher PI concentrations, although 18+/-7% of the amount of unconjugated PI was decomposed during incubation. We conclude that in humans PI is partially excreted as PI-O-glucuronide and that enzymatic hydrolysis extends the time of detectability for PI in urine samples.

  19. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [{sup 123}I]FP-CIT binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Knol, R.J.J.; Booij, J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Graduate School of Neurosciences, Amsterdam (Netherlands); Bruin, K. de; Eck-Smit, B.L.F. van [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    2008-03-15

    [{sup 123}I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [{sup 123}I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [{sup 123}I]FP-CIT. Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [{sup 123}I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [{sup 123}I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [{sup 123}I]FP-CIT binding to DATs. No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [{sup 123}I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of

  20. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    Science.gov (United States)

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  1. Amelioration of early radiation effects in oral mucosa (mouse) by intravenous or subcutaneous administration of amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, G. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Doerr, W. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Experimental Center, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany)

    2006-10-15

    Purpose: to quantify the reduction of radiation-induced oral mucositis by amifostine as a function of administration route. Material and methods: mucosal ulceration of lower mouse tongue epithelium was analyzed. Amifostine was injected at 1.8 mg/injection subcutaneously (s.c.) or intravenously (i.v.), 45 min or 10 min prior to irradiation. With single-dose irradiation, a single amifostine injection was given. During daily fractionated irradiation (5 x 3 Gy) for 1 week, amifostine was administered s.c. or i.v. twice (days 0, 3), or s.c. on all irradiation days (days 0-4). With ten fractions over 2 weeks, five s.c. injections were given in week 1 (days 0-4) or week 2 (days 7-11), or both. Two i.v. injections were given either in week 1 (days 0, 3) or week 2 (days 7, 10). All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. Results: in a single-dose control experiment, the ED{sub 50} (dose after which ulcer induction is expected in 50% of the mice) was 11.7 {+-} 1.4 Gy. Intravenous application of amifostine increased the ED{sub 50} to 14.0 {+-} 1.4 Gy (p = 0.024), while s.c. administration had no significant effect. The ED{sub 50} for test irradiation after 5 x 3 Gy was 5.8 {+-} 1.4 Gy. Two s.c. or i.v. amifostine injections yielded ED{sub 50} values of 7.2 {+-} 1.1 Gy (p = 0.0984) or 7.6 {+-} 1.2 Gy (p = 0.0334); five s.c. injections increased the ED{sub 50} to 8.2 {+-} 0.9 Gy (p = 0.0039). The ED{sub 50} after 10 x 3 Gy/2 weeks was 6.6 {+-} 1.8 Gy. Subcutaneous or intravenous administration of amifostine in week 1 yielded a significant increase in ED{sub 50} to 9.4 {+-} 2.5 Gy (p = 0.0099) and 10.0 {+-} 2.2 Gy (p = 0.0014). By contrast, amifostine administration in week 2 had no significant effect. Administration in weeks 1 and 2 resulted in an ED{sub 50} of 10.8 {+-} 3.6 Gy (p= 0.0053). Conclusion: amifostine during daily fractionated irradiation is effective only if administered in the initial treatment phase, i

  2. Morphine and codeine in oral fluid after controlled poppy seed administration.

    Science.gov (United States)

    Concheiro, Marta; Newmeyer, Matthew N; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A; Huestis, Marilyn A

    2015-07-01

    Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45 g raw poppy seed doses, each containing 15.7 mg morphine and 3.1 mg codeine, 8 h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1 µg/L morphine and codeine limits of quantification). Specimens (n = 459) were collected before and up to 32 h after the first dose. All specimens screened positive 0.5 h after dosing and remained positive for 0.5-13 h at Draeger 20 µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6 µg/L, with times to Cmax (Tmax ) of 0.5-1 h and 0.5-2.5 h post-dose, respectively. Windows of detection after the second dose extended at least 24 h for morphine and to 18 h for codeine. After both doses, the last morphine positive OF result was 1 h with 40 µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5 h with 95 µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1 h after ingestion of 15.7 mg of morphine in raw poppy seeds, depending on the cut-off employed.

  3. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

    Directory of Open Access Journals (Sweden)

    Kukulka M

    2017-02-01

    Full Text Available Michael Kukulka, Sai Nudurupati, Maria Claudia Perez Takeda Development Center Americas, Inc., Deerfield, IL, USA Background: Dexlansoprazole is a proton pump inhibitor (PPI approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT formulations.Aim: To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods: Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results: Equivalent values for area under the plasma concentration–time curve (AUC were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3% and were 12% higher in the fed state than in the fasted state. Conclusion: The AUC

  4. Benefits of oral and topical administration of ROQUETTE Chlorella sp. on skin inflammation and wound healing in mice.

    Science.gov (United States)

    Hidalgo-Lucas, Sophie; Bisson, Jean-Francois; Duffaud, Anais; Nejdi, Amine; Guerin-Deremaux, Laetitia; Baert, Blandine; Saniez-Degrave, Marie-Helene; Rozan, Pascale

    2014-01-01

    The human body is constantly exposed to the risk of traumatic lesions. Chlorella is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. In some communities, Chlorella is a traditional medicinal plant used for the management of inflammation-related diseases. ROQUETTE Chlorella sp. (RCs) was investigated by oral administration (125, 250 and 500 mg/kg) and cutaneous application (2.5, 5.0 and 10.0%) to evaluate its impact in two dermatological disorder models in mice: skin inflammation and wound healing. For skin inflammation, it was administered during 14 days starting one week before the induction of chronic skin inflammation by repeated cutaneous application of 12-Otetradecanoylphorbol 13-acetate (TPA). For wound healing the microalgae was administered by topical application after scarification of the skin until complete wound healing. Results indicated that oral and topical administrations of the two higher doses of RCs had significant effects on macroscopic score of skin inflammation with an efficient effect on microscopic score with cutaneous application. The microalgae had also efficient effect on healing process and duration of wound healing for both administration routes and particularly at the two highest doses of RCs. These findings suggest that administration of RCs by both oral and topical routes appeared to have beneficial effects on skin lesions.

  5. The oral administration of D-galactose induces abnormalities within the mitochondrial respiratory chain in the brain of rats.

    Science.gov (United States)

    Budni, Josiane; Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; da Silva, Sabrina; Luz, Aline Pereira da; Schiavo, Gustavo Luiz; Batista-Silva, Hemily; Scaini, Giselli; Streck, Emílio Luiz; Quevedo, João

    2017-02-24

    D-Galactose (D-gal) chronic administration via intraperitoneal and subcutaneous routes has been used as a model of aging and Alzheimer disease in rodents. Intraperitoneal and subcutaneous administration of D-gal causes memory impairments, a reduction in the neurogenesis of adult mice, an increase in the levels of the amyloid precursor protein and oxidative damage; However, the effects of oral D-gal remain unclear. The aim of this study was to evaluate whether the oral administration of D-gal induces abnormalities within the mitochondrial respiratory chain of rats. Male Wistar rats (4 months old) received D-gal (100 mg/kg v.o.), during the 1st, 2nd, 4th, 6th or 8th weeks by oral gavage. The activity of the mitochondrial respiratory chain complexes was measured in the 1st, 2nd, 4th, 6th and 8th weeks after the administration of D-gal. The activity of the respiratory chain complex I was found to have increased in the prefrontal cortex and hippocampus in the 1st, 6th and 8th weeks, while the activity of the respiratory chain complex II increased in the 1st, 2nd, 4th, 6th and 8th weeks within the hippocampus and in the 2nd, 4th, 6th and 8th weeks within the prefrontal cortex. The activity of complex II-III increased within the prefrontal cortex and hippocampus in each week of oral D-gal treatment. The activity of complex IV increased within the prefrontal cortex and hippocampus in the 1st, 2nd, 6th and 8th weeks of treatment. After 4 weeks of treatment the activity increased only in hippocampus. In conclusion, the present study showed that the oral administration of D-gal increased the activity of the mitochondrial respiratory chain complexes I, II, II-III and IV in the prefrontal cortex and hippocampus. Furthermore, the administration of D-gal via the oral route seems to cause the alterations in the mitochondrial respiratory complexes observed in brain neurodegeneration.

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

    OpenAIRE

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

    2011-01-01

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

  7. 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

  8. Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Oliver, S; Johnson, M; Ward, C; Cheon, A J; Choo, Y S; Kim, I C

    2000-06-01

    Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

  9. Body and Testicular Weight Changes in Adult Wistar Rats Following Oral Administration of Artesunate

    Directory of Open Access Journals (Sweden)

    al-hassan m. izunya

    2010-05-01

    Full Text Available This experiment was designed to study the effects on the body and testicular weights of adult wistar rats that recieved an oral administration of normal and double normal doses of artesunate. The rats were divided into three groups (A, B and C of five rats each. A and B served as the treatment groups, while C served as the control group. Group A rats were given 4mg.kg-1 b.w of artesunate daily for 3 days followed by 2mg.kg-1 b.w daily for next for 4 days. Group B rats were given 8mg.kg-1 b.w of artesunate daily for 3 days followed by 4mg.kg-1 b.w daily for next 4 days, while group C rats were given only distilled water. The rats were fed with grower's mash purchased from Edo feeds and Flour Mill Ltd, Ewu, Edo state and were given w ater ad libitum. On day eight of the experiment, the rats were weighed and sacrificed. The testes w ere carefully dissected out, freed from adherent tissues and weighed to the nearest 0.001 g. The results showed no changes in body weight of rats in groups A, B and C. There was also no significant change in testicular weight of rats in group A. However a significant increase in testicular weight was observed in group C. Our results suggest that artesunate at normal and double normal doses, has no effect on body weight of rats but may be toxic to the testes at higher doses. It is uncertain however if these changes are reversible. It is recommended therefore, that further studies aimed at corroborating these observations be carried out.

  10. Oral Self-Administration Of EtOH In Transgenic Mice Lacking Beta-Endorphin

    Directory of Open Access Journals (Sweden)

    Stephani Allen

    2007-01-01

    Full Text Available EtOH modifies the production and/or release of endogenous opioid peptides, including -endorphin (Gianoulakis, 2004; Przewlocka et al., 1994; Schulz et al., 1980. Opioids subsequently influence the reinforcing properties of EtOH and the development of alcoholism (Terenius, 1996; Van Ree, 1996. In this study, beta-endorphin deficient mutant mice were used to examine the effects of a specific opioid peptide on EtOH consumption. Mice were obtained from The Jackson Laboratory, Bar Harbor, ME, USA. Male and female, adult naïve mice were single housed in Plexiglas cages with corn cob bedding and ad lib access to food (mouse chow and water. A two-bottle free choice EtOH oral self-administration paradigm was administered to homozygous mutant mice (void of all beta-endorphin, heterozygous mice (50% beta-endorphin expression, and sibling wildtype mice (C57BL/6J. Subjects received increasing concentrations of EtOH (0%, 3%, 6%, 12%, and 15% each given over an eight day span, and were evaluated for preference and consumption each day. Bottles were switched every other day to avoid the development of a side preference. Overall, females drank more than males. Homozygous mutant mice (KO showed decreased preference for EtOH at all concentrations, and self-administered significantly less than heterozygous mice (HT and wildtype mice (C57. The HTs had a tendency to drink the most followed by the C57s, and the KOs drank the least. These data support the hypothesis that beta-endorphin influences the reinforcing effects of EtOH.

  11. Comparison of Anticoagulant Effects on Vein Grafts between Human TFPI Gene Transfection and Aspirin Oral Administration

    Institute of Scientific and Technical Information of China (English)

    Deguang FENG; Cheng ZHOU; Quan LI; Kailin ZHANG; Xionggang JIANG; Song LENG; Heping DENG; Jiane FENG; Tucheng SUN; Long WU

    2008-01-01

    To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg·kg-1·d-1) was administered (I.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gone expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. R was suggested that the anticoagulant effects on vein grafts of human TFPI gene trans- fection are better than those of aspirin.

  12. Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children.

    Science.gov (United States)

    Kersten, E; Barry, A; Klein, S

    2016-03-01

    Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development.

  13. SiRNA In Vivo-Targeted Delivery to Murine Dendritic Cells by Oral Administration of Recombinant Yeast.

    Science.gov (United States)

    Xu, Kun; Liu, Zhongtian; Zhang, Long; Zhang, Tingting; Zhang, Zhiying

    2016-01-01

    SiRNA therapeutics promise a future where any target in the transcriptome could be potentially addressed. However, the delivery of SiRNAs and targeting of particular cell types or organs are major challenges. A novel, efficient, and safe delivery system for promising the introduction of SiRNAs into particular cell types within living organisms is of great significance. Our previous studies have proved that recombinant protein (MSTN) and exogenous gene (EGFP) as vaccines, and furthermore functional CD40 shRNA expression can be delivered into dendritic cells (DCs) in mouse by oral administration of recombinant yeast (Saccharomyces cerevisiae). Here, we describe the details of the promising and innovative approach based on oral administration of recombinant yeast that allows in vivo-targeted delivery of functional SiRNA to murine intestinal DCs.

  14. 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

    induce stress and this may also influence parameters under study. Different methods for voluntary oral dosing has been described in the literature, among the methods proposed as an alternative to oral gavage is dosing in chocolate cream, sucker water etc. In this study we used jellybeans to give...

  15. The effect of oral sodium acetate administration on plasma acetate concentration and acid-base state in horses

    Directory of Open Access Journals (Sweden)

    Lindinger Michael I

    2007-12-01

    Full Text Available Abstract Aim Sodium acetate (NaAcetate has received some attention as an alkalinizing agent and possible alternative energy source for the horse, however the effects of oral administration remain largely unknown. The present study used the physicochemical approach to characterize the changes in acid-base status occurring after oral NaAcetate/acetic acid (NAA administration in horses. Methods Jugular venous blood was sampled from 9 exercise-conditioned horses on 2 separate occasions, at rest and for 24 h following a competition exercise test (CET designed to simulate the speed and endurance test of 3-day event. Immediately after the CETs horses were allowed water ad libitum and either: 1 8 L of a hypertonic NaAcetate/acetic acid solution via nasogastric tube followed by a typical hay/grain meal (NAA trial; or 2 a hay/grain meal alone (Control trial. Results Oral NAA resulted in a profound plasma alkalosis marked by decreased plasma [H+] and increased plasma [TCO2] and [HCO3-] compared to Control. The primary contributor to the plasma alkalosis was an increased [SID], as a result of increased plasma [Na+] and decreased plasma [Cl-]. An increased [Atot], due to increased [PP] and a sustained increase in plasma [acetate], contributed a minor acidifying effect. Conclusion It is concluded that oral NaAcetate could be used as both an alkalinizing agent and an alternative energy source in the horse.

  16. 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...

  17. 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.

  18. A Case Report of Post-Operative Jöd-Basedow Phenomennon Following Oral and IV Iodine Contrast Administration

    Directory of Open Access Journals (Sweden)

    Maureen Higgs

    2014-01-01

    Full Text Available This is a case of thyrotoxicosis, due to the Jöd-Basedow phenomenon following administration of oral and IV iodinated contrast in a patient with history of gastrointestinal stromal tumor (GIST and small bowel obstruction. The patient developed atrial fibrillation and had an extended stay in the intensive care unit. Given the aging population with possible subclinical hyperthyroidism, multinodular goiter, and the rise in contrast administration for routine diagnostic studies, this case serves to raise awareness of the risks of “routine” tests administered to our aging patient population.

  19. Study on pharmacokinetics of Amygdalin after oral administration of semen persicae extraction in rat plasma by HPLC

    OpenAIRE

    Zhang, Zhidan; Gao, Wenyuan; Ma, Chaoyi; Liu, Changxiao

    2011-01-01

    Semen Persicae was a traditional Chinese medicine for the treatment of diseases such as inflammation and hyperlipemia. Amygdalin was one of the main active ingredients of this traditional Chinese medicine. In this paper, pharmacokinetic study was conducted to obtain pharmacokinetic parameters of amygadalin after oral administration of Semen Persicae extraction in rat plasma. HPLC-UV was used to determine the concentration of amygdalin in rat plasma at different time points after administratio...

  20. A comparative study on sublingual versus oral and vaginal administration of misoprostol for late first and early second trimester abortion.

    Science.gov (United States)

    Ganguly, Rajendra Prasad; Saha, Shyama Prasad; Mukhopadhyay, Sima; Bhattacharjee, Nabendu; Bhattacharyya, Subir Kumar; Patra, Kajal Kumar

    2010-05-01

    To compare the effectiveness, side-effects and outcome of sublingual with oral and vaginal administrations of misoprostol for induction of abortion in late first and early second trimester of gestation (9 to 16 weeks), a comparative observational study was carried out among 258 women with a period of gestation between 9 and 16 weeks, scheduled to have medical abortion, and randomly allocated into three groups and offered sublingual, oral and vaginal routes of misoprostol administration (400 mcg of misoprostol 6 hourly, maximum up to four dosages) respectively. Primary outcome measure was complete abortion rate and the secondary outcome measures were incidence of cases where surgical evacuation required, failure rate and induction-abortion interval. Development of side-effects and subjective assessment of patient's comfort with the different routes of administration were also recorded. Rate of complete abortion was higher in sublingual group in comparison to oral (p = 0.0338) and vaginal route (p = 0.5627). Surgical evacuation was required in less number of cases in sublingual group. Induction-abortion interval was also least with the sublingual route le, p route and least with the sublingual route. The patients were least comfortable with the vaginal route. Gastro-intestinal side-effects were least with the vaginal route, but significant vaginal bleeding (> 250 ml) was little bit higher with this route. Though misoprostol is effective in inducing medical abortion irrespective of the route of administration, sublingual route gives better results as compared to oral (statistically significant) and vaginal routes (in some respects, not of much statistical significance).

  1. Comparative Pharmacokinetic Study of Mangiferin After Oral Administration of Pure Mangiferin and US Patented Polyherbal Formulation to Rats

    OpenAIRE

    Kammalla, Ananth Kumar; Ramasamy, Mohan Kumar; Inampudi, Jyothi; Dubey, Govind Prasad; Agrawal, Aruna; Kaliappan, Ilango

    2014-01-01

    The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg...

  2. Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation

    OpenAIRE

    ODORE, R; De Marco, M.; Gasco, L.; Rotolo, L.; Meucci, V.; Palatucci, A. T.; Rubino, V.; Ruggiero, G.; Canello, S.; Guidetti, G; Centenaro, S.; A. Quarantelli; Terrazzano, G.; A. Schiavone

    2015-01-01

    Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-d...

  3. Separation and Determination of Methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection

    Institute of Scientific and Technical Information of China (English)

    WANG An-bao; Joseph F. Foss; YUAN Chun-su; Joachim Osinski

    2005-01-01

    A high performance liquid chromatography(HPLC) method coupled with electrochemical detection and solid phase extraction is described for the separation and determination of methylnaltrexone(MNTX), a quaternary opioid antagonist, in human clinical plasma samples after oral administration. Linearity of the standard curve for MNTX was found in the range of 4.0_150 ng/mL and was statistically conformed. The correlation coefficient(r2) and calibration equation obtained from linear regression analysis are 0.9999 and Y=54.27X-0.22, where Y and X represent the peak area and concentration of MNTX, respectively. The detection limit of MNTX under the present experimental conditions is 2.0 ng/mL by estimating at a ratio of 3 of signal to noise. The mean recovery of MNTX in human plasma is higher than 97%. The analytical method was applied to the pharmacokinetic determination of MNTX after single dose oral administration. These data demonstrate that the change of MNTX plasma concentration versus time is obvious. MNTX level of plasma reaches to a plateau between 45 to 120 minutes and then falls slowly. The content of MNTX in plasma sample maintains at an obviously detectable level after twelve hours of oral administration. The pharmacokinetic parameters for a single dose of 19.2 mg/kg in plasma are cmax=206.42(±16.53) ng/mL and tmax=60 min.

  4. Enhanced mucosal and systemic immune response with squalane oil-containing multiple emulsions upon intranasal and oral administration in mice.

    Science.gov (United States)

    Shahiwala, Aliasgar; Amiji, Mansoor M

    2008-05-01

    The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.

  5. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

    Indian Academy of Sciences (India)

    Y-J Choi; J Y Kim; S B Yoo; J-H Lee; J W Jahng

    2013-09-01

    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 counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  6. Administration of Coagulation-Altering Therapy in the Patient Presenting for Oral Health and Maxillofacial Surgery.

    Science.gov (United States)

    Halaszynski, Thomas M

    2016-11-01

    Oral health care providers are concerned with how to manage patients prescribed coagulation-altering therapy during the perioperative/periprocedural period for dental and oral surgery interventions. Management and recommendation can be based on medication pharmacology and the clinical relevance of coagulation factor levels/deficiencies. Caution should be used with concurrent use of medications that affect other components of the clotting mechanisms; prompt diagnosis and any necessary intervention to optimize outcome is warranted. However, evidence-based data on management of anticoagulation therapy during oral and maxillofacial surgery/interventions is lacking. Therefore, clinical understanding and judgment are needed along with appropriate guidelines matching patient- and intervention-specific recommendations.

  7. Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick

    2010-06-01

    To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.

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

    Science.gov (United States)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte; Gejl, Michael; Rungby, Jørgen; Larsen, Agnete

    2016-01-01

    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) analog, 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 2 days before severe trauma was induced with a stereotactic cryo-lesion. At 2 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% (p < 0.05). Calpain-driven necrotic tone was reduced ~2-fold in sitagliptin-treated brains (p < 0.001) and activation of the protective cAMP-response element binding protein (CREB) system was significantly more pronounced (~1.5-fold, p < 0.05). The CREB-regulated, mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) was increased in sitagliptin-treated mice (p < 0.05). 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 analogs in models of brain damage relates to GLP-1 receptor stimulation in a dose-dependent manner.

  9. 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, J. K.; Mehrdana, F.; Hansen, Egon Bech;

    2016-01-01

    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....... disease caused by this pathogen either following i.p. injection or by oral administration (in feed). It was found that injection of CAP18 into juvenile rainbow trout before exposure to Y. ruckeri was associated with lowered mortality compared to non-medicated fish although it was less effective than...

  10. Engineered nanoparticulate drug delivery systems: the next frontier for oral administration?

    Science.gov (United States)

    Diab, Roudayna; Jaafar-Maalej, Chiraz; Fessi, Hatem; Maincent, Philippe

    2012-12-01

    For the past few decades, there has been a considerable research interest in the area of oral drug delivery using nanoparticle (NP) delivery systems as carriers. Oral NPs have been used as a physical approach to improve the solubility and the stability of active pharmaceutical ingredients (APIs) in the gastrointestinal juices, to enhance the intestinal permeability of drugs, to sustain and to control the release of encapsulated APIs allowing the dosing frequency to be reduced, and finally, to achieve both local and systemic drug targeting. Numerous materials have been used in the formulation of oral NPs leading to different nanoparticulate platforms. In this paper, we review various aspects of the formulation and the characterization of polymeric, lipid, and inorganic NPs. Special attention will be dedicated to their performance in the oral delivery of drug molecules and therapeutic genes.

  11. Absence of food effect on the pharmacokinetics of telbivudine following oral administration in healthy subjects.

    Science.gov (United States)

    Zhou, Xiao-Jian; Lloyd, Deborah M; Chao, George C; Brown, Nathaniel A

    2006-03-01

    The influence of food on the pharmacokinetics of telbivudine, a candidate antiviral agent against hepatitis B virus (HBV), was investigated in healthy adult subjects following a 600-mg oral dose administered with and without a high-fat/high-calorie meal. Telbivudine was well tolerated under fasting and fed conditions. Oral absorption of telbivudine as measured by maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC(0-t) and AUC(0-infinity)) was not altered by food intake immediately before oral dosing. Values of Cmax, Tmax, and AUC were comparable when telbivudine was administered under fed and fasting conditions. Results from this study indicated that the absorption of telbivudine was not affected by a high-fat/high-calorie meal; telbivudine can therefore be administered orally with no regard to the timing of meals.

  12. Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients.

    Science.gov (United States)

    Sakurada, Tsutomu; Oishi, Daisuke; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

    2013-10-01

    Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty-six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients.

  13. Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes.

    Science.gov (United States)

    Hostrup, M; Kalsen, A; Auchenberg, M; Bangsbo, J; Backer, V

    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 included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. 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 salbutamol increased (P 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 benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports.

  14. Histological study of the effects of oral administration of datura metel on the visual system of male wistar rats

    Directory of Open Access Journals (Sweden)

    Ibiyeye Yetunde Rukayat

    2012-08-01

    Full Text Available This study was carried out in order to elucidate some of the effects of oral administration of Cannabis sativa on the visual system of male Wistar rats as marker of toxicity using neurohistochemical study. 12 adult male Wistar rats were used for this study. The rats were distributed into two groups (A and B. The rats in group A served as the treatment group and were administered with 300 mg/kg body weight of Cannabis sativa while the rats in group B which served as the control were administered with equal volume of phosphate buffered saline. The duration of administration was for 14d. The rats were sacrificed using cervical dislocation 24 hrs after the last administration. The brains were excised from the skulls of the animals and were completely fixed in 10% formol calcium. 72 hours after fixation, right occipital cortex, right lateral geniculate nucleus and right superior colliculus were excised separately for histological (H&E processing. Microscopic observations made from the permanent photomicrographs revealed alterations in the histoarchitecture of the visual system of the rats in the treated group compared with the rats in the treated group with preserved histological outline. Oral administration of Cannabis sativa on the visual system of male Wistar rats caused neurodegeneration of the occipital cortex, right lateral geniculate nucleus and right superior colliculus of Wistar rats.

  15. Oral administration of γ-aminobutyric acid affects heat production in a hot environment in resting humans

    Directory of Open Access Journals (Sweden)

    Miyazawa Taiki

    2012-02-01

    Full Text Available Abstract Background Central administration of γ-amino butyric acid (GABA induces lower body temperature in animals in hot ambient air. However, it is still unknown whether oral GABA administration affects temperature regulation at rest in a hot environment in humans. Therefore, in the present study, we specifically hypothesized that systemic administration of GABA in humans would induce hypothermia in a hot environment and that this response would be observed in association with decreased heat production. Methods Eight male participants drank a 200-ml sports drink with 1 g of GABA (trial G or without GABA (trial C, then rested for 30 minutes in a sitting position in a hot environment (ambient air temperature 33°C, relative humidity 50%. Results We found that changes in esophageal temperature from before drinking the sports drink were lower in trial G than in trial C (-0.046 ± 0.079°C vs 0.001 ± 0.063°C; P 2 vs 47 ± 8 W/m2; P Conclusions In this study, we have demonstrated that a single oral administration of GABA induced a larger decrease in body core temperature compared to a control condition during rest in a hot environment and that this response was concomitant with a decrease in total heat production.

  16. The effects of co-administration of butter on the absorption, metabolism and excretion of catechins in rats after oral administration of tea polyphenols.

    Science.gov (United States)

    Zhang, Liang; Han, Yuhui; Xu, Liwei; Liang, Yuhong; Chen, Xin; Li, Junsong; Wan, Xiaochun

    2015-07-01

    In Southwest China, tea polyphenols are usually utilized by way of butter tea. Tea polyphenols inhibit the absorption and biosynthesis of fatty acids in vivo, but the effects of butter on the pharmacokinetics of tea polyphenols have drawn less concern. A rapid UHPLC-MS/MS method was used to quantitatively determine the catechins in the plasma, feces and bile of rats after the oral administration of tea polyphenol or its combination with butter. In comparison with the single tea polyphenol treatment, the maximum plasma concentrations (Cmax) of the free EGCG, EGC, EC, GCG, GC and ECG significantly decreased after the co-administration of butter. The mean residence times (MRT) of the free EGCG, EGC, EC, GC and ECG were also significantly prolonged. When the plasma samples were treated with β-glucuronidase and arylsulfatase, the pharmacokinetic parameters of the total catechins (free and conjugated forms) were not affected by the co-administration of butter. These results indicated that the total absorption of catechins was not affected by butter, but the metabolism of catechins had been changed. Furthermore, the fecal catechins were significantly increased by butter. The total fecal amount and excretion ratio of all catechins were increased highly. The biliary excretion of EGCG, EGC, EC, GCG and GC was significantly increased by the co-administration of butter. To sum up, the butter changed the metabolism of catechins in vivo by decreasing the plasma concentration of the free catechins but increasing the conjugated catechins.

  17. 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...

  18. In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration.

    Science.gov (United States)

    Yang, Kai; Gong, Hua; Shi, Xiaoze; Wan, Jianmei; Zhang, Youjiu; Liu, Zhuang

    2013-04-01

    Graphene oxide (GO) and its functionalized derivatives have attracted great attention in biomedicine in recent years. A number of groups including ours have studied the in vivo behaviors of functionalized nano-graphene after intravenous injection or inhalation, and uncovered the surface coating & size dependent biodistribution and toxicology profiles for this type of nanomaterials. However, the fate of GO derivatives in animals after oral feeding and intraperitoneal (i.p.) injection, which are two other major drug administration routes, remain unclear. Therefore, in this work, we sought to systematically investigate in vivo biodistribution and potential toxicity of as-made GO and a number of polyethylene glycol (PEG) functionalized GO derivatives with different sizes and surface coatings, after oral and intraperitoneal administration at high doses. It is found that (125)I labeled PEGylated GO derivatives show no obvious tissue uptake via oral administration, indicating the rather limited intestinal adsorption of those nanomaterials. In contrast, high accumulation of PEGyalted GO derivatives, but not as-made GO, in the reticuloendothelial (RES) system including liver and spleen is observed after i.p. injection. Further investigations based on histological examination of organ slices and hematological analysis discover that although GO and PEGylated GO derivatives would retain in the mouse body over a long period of time after i.p. injection, their toxicity to the treated animals is insignificant. Our work is an important fundamental study that offers a deeper understanding of in vivo behaviors and toxicology of functionalized nano-graphene in animals, depending on their different administration routes.

  19. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration.

    Science.gov (United States)

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Boyd, Ben J

    2011-07-30

    This study is the first to demonstrate the ability of nanostructured liquid crystal particles to sustain the absorption of a poorly water soluble drug after oral administration. Cubic (V(2)) liquid crystalline nanostructured particles (cubosomes) formed from phytantriol (PHY) were shown to sustain the absorption of cinnarizine (CZ) beyond 48h after oral administration to rats. Plasma concentrations were sustained within the range of 21.5±1.5ng/mL from 12 to 48h. In stark contrast, cubosomes prepared using glyceryl monooleate (GMO) did not sustain the absorption of CZ and drug concentrations fell below quantifiable levels after 24h. Sustained absorption of CZ from PHY cubosomes lead to a significant enhancement (pdegradation of the LC nanostructure may limit sustained drug release. In addition, PHY cubosomes were shown to be extensively retained in the stomach (>24h) leading to the conclusion that in the case of non-digestible PHY cubosomes, the stomach may act as a non-sink reservoir that facilitates the slow release of poorly water soluble drugs, highlighting the potential use of non-digestible LC nanostructured particles as novel sustained oral drug delivery systems.

  20. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

    Science.gov (United States)

    Choi, Jonghye; Kim, Heyjin; Kim, Pilje; Jo, Eunhye; Kim, Hyun-Mi; Lee, Moo-Yeol; Jin, Seon Mi; Park, Kwangsik

    2015-01-01

    Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

  1. Pharmacokinetic Profiles of Active Components After Oral Administration of a Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers.

    Science.gov (United States)

    Sadakane, Chiharu; Watanabe, Junko; Fukutake, Miwako; Nisimura, Hiroaki; Maemura, Kazuya; Kase, Yoshio; Kono, Toru

    2015-11-01

    Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future.

  2. Prions efficiently cross the intestinal barrier after oral administration: Study of the bioavailability, and cellular and tissue distribution in vivo

    Science.gov (United States)

    Urayama, Akihiko; Concha-Marambio, Luis; Khan, Uffaf; Bravo-Alegria, Javiera; Kharat, Vineetkumar; Soto, Claudio

    2016-01-01

    Natural forms of prion diseases frequently originate by oral (p.o.) infection. However, quantitative information on the gastro-intestinal (GI) absorption of prions (i.e. the bioavailability and subsequent biodistribution) is mostly unknown. The main goal of this study was to evaluate the fate of prions after oral administration, using highly purified radiolabeled PrPSc. The results showed a bi-phasic reduction of PrPSc with time in the GI, except for the ileum and colon which showed sustained increases peaking at 3–6 hr, respectively. Plasma and whole blood 125I-PrPSc reached maximal levels by 30 min and 3 hr, respectively, and blood levels were constantly higher than plasma. Upon crossing the GI-tract 125I-PrPSc became associated to blood cells, suggesting that binding to cells decreased the biological clearance of the agent. Size-exclusion chromatography revealed that oligomeric 125I-PrPSc were transported from the intestinal tract, and protein misfolding cyclic amplification showed that PrPSc in organs and blood retained the typical prion self-replicating ability. Pharmacokinetic analysis found the oral bioavailability of 125I-PrPSc to be 33.6%. Interestingly, 125I-PrPSc reached the brain in a quantity equivalent to the minimum amount needed to initiate prion disease. Our findings provide a comprehensive and quantitative study of the fate of prions upon oral infection. PMID:27573341

  3. Difficulties in administration of oral medication formulations to pet cats: an e-survey of cat owners.

    Science.gov (United States)

    Sivén, M; Savolainen, S; Räntilä, S; Männikkö, S; Vainionpää, M; Airaksinen, S; Raekallio, M; Vainio, O; Juppo, A M

    2017-03-11

    The purpose here was to determine the problems cat owners encounter in medicating their cats with orally administered drugs at home. The study was carried out as an open e-questionnaire survey addressed to cat owners in which the authors focused on the oral administration route. A total of 46 completed questionnaires were included in the survey. In the study, 46 cats received 67 orally administered drugs. Approximately half of the drugs were registered for use in cats by the European Medicines Agency (54 per cent), and there were also off-label drugs registered for human (36 per cent) and canine medication (7.4 per cent) and an ex tempore drug (3.0 per cent). The owners were unable to give the doses as prescribed for their cats for one-fourth of the medications (16/67). Drugs that were registered for feline medication were significantly more palatable than drugs registered for other species (odds ratio (OR) 4.9), and liquid formulations were significantly more palatable than solid formulations (OR 4.8). However, most of the owners (22/38) preferred a solid dosage form, while few (4/38) chose a liquid formulation. The results indicate that there is still a need for more palatable and easily administered oral drugs for cats.

  4. 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...

  5. Oral Administration of Apigenin Inhibits Metastasis through AKT/P70S6K1/MMP-9 Pathway in Orthotopic Ovarian Tumor Model

    OpenAIRE

    Bing-Hua Jiang; Ling-Zhi Liu; Xu Qian; Chongyong Li; Jun He; Min Wang; Qing Xu; Zhumei Shi

    2012-01-01

    Apigenin, a flavonoid commonly present in the daily diet, is known for its potential anti-tumor properties. However, the effect of apigenin via oral administration on tumor growth and metastasis remains unknown. In this study we developed an orthotopic ovarian tumor model in nude mice to test the effect of apigenin oral administration, and showed that apigenin inhibited the micrometastasis of cancer cells in the animal tumor model. To understand the mechanism of apigenin in inhibiting metasta...

  6. No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice.

    Science.gov (United States)

    Taylor, Julia A; Welshons, Wade V; Vom Saal, Frederick S

    2008-02-01

    Route of administration of chemicals in adults is an important factor in pharmacokinetics of chemicals such as bisphenol A (BPA), the monomer with estrogenic activity used to make polycarbonate plastic products and to line food and beverage cans. Based on findings in adults it has been proposed (CERHR, 2007) that non-oral routes of administration in newborn rodents would also lead to high exposure relative to oral administration. However, in fetuses and neonates, the enzyme that conjugates BPA (UDP-glucuronosyltransferase) is expressed at low levels, suggesting that there may be no differences in pharmacokinetics between oral and non-oral dosing. We thus conducted an analysis of plasma concentrations of unconjugated 3H-BPA after HPLC separation in postnatal day 3 female mice throughout the 24h after administering 3H-BPA orally or via subcutaneous injection at doses above and below the current EPA reference dose. We found no significant difference in plasma BPA based on route of administration in neonatal mice at either dose. However, compared to data from other studies conducted with adults, there was a markedly higher plasma BPA level after oral administration of BPA in newborn mice. This finding sets aside the belief that non-oral administration of BPA renders data as not suitable for consideration of the hazard posed by low-dose exposure to BPA during neonatal life. Therefore the large numbers of BPA studies that used non-oral administration at very low doses during the neonatal period should not be dismissed by scientists or the regulatory community based on route of administration.

  7. 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.

  8. Comparison of the effectivity of oral and intra-articular administration of tenoxicam in patients with knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Mesut Erbas

    2015-10-01

    Full Text Available ABSTRACTBACKGROUND AND OBJECTIVES:Tenoxicam is widely used in osteoarthritis treatment and we aimedto compare the effectivity of oral and intra-articular administration of tenoxicam in osteoarthri-tis treatment.METHODS: This study was performed between 2011 and 2012 by retrospectively analyzing andcomparing the findings of 60 patients who were clinically and radiologically diagnosed with kneedegenerative osteoarthritis in Bünyan state hospital pain policlinic. 60 patients included in thestudy were divided into two groups. The first group (tenoxicam IA, n = 30 included patientfindings of those subjected to intra-articular injection of 20 mg tenoxicam to the knee oncea week for three weeks and the second group (oral tenoxicam, n = 30 included patients whowere administered 20 mg oral tenoxicam once a day for three weeks. All patients were clini-cally evaluated pre-treatment and in the 1st week, 1st month and 3rd month post-treatmentaccording to specified criteria.RESULTS AND CONCLUSIONS: Twenty two of 60 patients included in the study were male and 38were female. In both groups significant improvements were detected in all of the observedparameters: visual analog scale, Western Ontario McMaster Osteoarthritis Index (pain, physicalactivity, knee stiffness and Lequesne index scores and in the evaluations performed in 1st week,1st month and 3rd month with respect to pre-treatment values. Besides, a better complianceto treatment and gastrointestinal system tolerability in tenoxicam IA group was also observed.Intra-articular tenoxicam administration could be thought as an alternative treatment methodin patients with knee osteoarthritis who cannot use oral tenoxicam especially due to systemicgastrointestinal system side effects and those who have difficulties in adapting to treatment.

  9. Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: interaction with the transporters on Caco-2 cells.

    Science.gov (United States)

    Katragadda, Suresh; Jain, Ritesh; Kwatra, Deep; Hariharan, Sudharshan; Mitra, Ashim K

    2008-10-01

    In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied. In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately five-fold increase in area under the curve (AUC) values relative to ACV (pACV. C(last(T)) (concentration at the last time point) of SACV was observed to be 0.18+/-0.06 microM in plasma which is two times better than VACV and three times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (C(max)) and eliminated at varying rates (lambda(z)) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections.

  10. Immune response elicited by the oral administration of an intermediate strain of IBDV in chickens

    Directory of Open Access Journals (Sweden)

    Juan Manuel Carballeda

    2014-12-01

    Full Text Available The immune response elicited by the oral inoculation of an intermediate strain of infectious bursal disease virus was studied in chickens. A strong over expression of IL-6, IL-8, IFNα and IFNγ was observed in bursa at 3 days post inoculation together with an increase in splenic NO2 release. An influx of T-lymphocytes was also detected.

  11. 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 ...

  12. Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration.

    Science.gov (United States)

    Yang, F; Li, Z L; Shan, Q; Zeng, Z L

    2014-08-01

    The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high-performance liquid chromatography with a 0.005 μg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double-peak phenomenon was observed, and the first (Cmax1 ) and second (Cmax2) peaks were 1.99 ± 0.43 μg/mL at 2.0 h and 2.27 ± 0.38 μg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 μg/mL) was also observed, and initial concentration of 45.76 μg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half-life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady-state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.

  13. Oral Administration of Interferon Tau Enhances Oxidation of Energy Substrates and Reduces Adiposity in Zucker Diabetic Fatty Rats

    OpenAIRE

    Tekwe, Carmen D.; Lei, Jian; Yao, Kang; Rezaei, Reza; Li, Xilong; Dahanayaka, Sudath; Carroll, Raymond J.; Meininger, Cynthia J.; Bazer, Fuller W.; Wu, Guoyao

    2013-01-01

    Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4 or 8 μg IFNT/kg body weight (BW) per day (n=6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary g...

  14. Treatment of Psoriasis Vulgaris by Oral Administration of Yin Xie Ping Granules——A Clinical Report of 60 Cases

    Institute of Scientific and Technical Information of China (English)

    Chang Shan; Liu Yuan; Bo Xiuzhen; Qi Aiju

    2006-01-01

    @@ Psoriasis is a chronic and an easily recurrent dermatosis, with the characteristic red papules and patches covered with silvery scales especially on the outer aspects of the limbs, scalp, and back.1 The cause of the disease is not clear yet, and no satisfactory therapies are available for the treatment so far. We treated 60 cases of psoriasis vulgaris by oral administration of Yin Xie Ping Granules (银屑平颗粒 Granulae for Treating Psoriasis) from August 2004 to March 2005 with quite good results, with another 60 cases treated by taking Xiao Yin Pian (消银片 Tablets for Relieving Psoriasis) as the controls.A report follows.

  15. 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

    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...... 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...

  16. Oral Administration of T Cell Epitope Peptide Inhibits the Systemic IL-4 Response Elicited by an Egg-White Diet in a TCR Transgenic Mouse Model

    OpenAIRE

    HIRAIDE, Erika; NAKAJIMA-ADACHI, Haruyo; Hachimura, Satoshi

    2014-01-01

    Oral immunotherapy with T cell epitope peptides is a promising treatment for food allergy. We examined the effect of oral administration of an ovalbumin T cell epitope peptide (OVA323-339) in a TCR transgenic mouse model (OVA23-3 mice). OVA23-3 mice were fed egg-white diet containing ovalbumin and subsequently orally administrated the OVA323-339 peptide. Cytokine measurements revealed that the IL-4 production of splenic CD4+ T cells was significantly decreased by feeding the OVA323-339 peptid...

  17. 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

  18. Effect of Oral Administration of Tungsten Trioxide (WO3) Particles on Hispathological Feature of liver and kidney in Rat

    Science.gov (United States)

    Munawaroh, H. S. H.; Nandiyanto, A. B. D.; Gumilar, G. G.; Widi, A.; Subangkit, M.

    2017-03-01

    This study aims to investigate the toxicity and histopathology of tungsten trioxide (WO3) administration on rat’s liver and kidney. The LD50 of WO3 was determined and the sub acute toxicity was evaluated by orally administration of 5000 mg kg-1 of WO3 to rat for 14 consecutive days. Parameter of blood cells, ALT, creatinine, and BUN were experimentally measured. The toxicological evaluation showed that WO3 is a non toxic compound with the LD50 higher that 5000 mg kg-1. No biochemical change was observed for creatinine and Blood Urea Nitrogen parameter. In contrast, ALT parameter shows higher value in the experiment than that in the control group. Histopathological changes on rat’s liver and kidney were also studied. Small defects in rat’s liver and kidney were found, which may interfere the functional of related enzymes.

  19. 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.

  20. [Tissue and cell interactions in the oral mucosa after cytostatic drugs administration].

    Science.gov (United States)

    Bykov, V L; Leont'eva, I V

    2011-01-01

    In the preceding work ("Morphology", 2011, issue 2), the regularities of oral mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its further regeneration, were reviewed. This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of CSD effect on non-epithelial OM cell populations and their interactions with each other and the epithelium. The changes of intraepithelial tissue homeostasis, associated with CSD effect on intraepithelial lymphocytes, granulocytes, dendritic antigen presenting cells and melanocytes, interacting with epitheliocytes, are described. The data are presented, indicating that along with the epithelium, the cell populations of lamina propria and submucosal connective tissue, as well as the small blood vessels, are important targets of CSD in the OM tissues. The concept of a unifying model, describing tissue, cellular and molecular mechanisms of the oral mucositis development after CSD treatment, is reviewed.

  1. Preparation and in-vitro/in-vivo characterization of trans-resveratrol nanocrystals for oral administration.

    Science.gov (United States)

    Singh, Sandeep K; Makadia, Vishal; Sharma, Shweta; Rashid, Mamunur; Shahi, Sudhir; Mishra, Prabhat R; Wahajuddin, Mohammed; Gayen, Jiaur R

    2017-02-13

    Trans -resveratrol (t-RES) is a natural polyphenolic compound with extensive therapeutic activities; however, its clinical application is circumscribed due to its poor solubility and low bioavailability. The purpose of this study was to prepare stable t-RES nanocrystals (t-RES-NCs) with different stabilizers to improve its oral bioavailability. t-RES-NCs were fabricated by the probe sonication method and optimized by particles size, poly dispersive index and zeta potential. The pharmaceutical characterization of t-RES-NCs was further performed systematically. The in vitro cellular efficacy and in vivo pharmacokinetics of t-RES-NCs were also evaluated. The optimized NCs were successfully accomplished in a sub-micron particle size (110.28 ± 12.55 nm) with high ζ-potential (-32.96 ± 3.85 mV) value. Scanning electron microscopy (SEM) image indicated that morphology of t-RES-NCs was regular and rod like in shape. Meanwhile, the result of in vitro cellular efficacy against MDA-MB-231 cells revealed that developed t-RES-NCs were more efficacious and potent (p < 0.05) than plain t-RES. Compared to plain t-RES, t-RES-NCs exhibited significant increase (p < 0.05) in AUC0-t (3.5-folds) and C max (2.2-folds), demonstrating improved oral bioavailability of t-RES after grafting as NCs. The significant increase in oral bioavailability of developed t-RES-NCs represents an ideal vehicle for oral delivery of t-RES which ultimately reflected the clinical efficacy of t-RES.

  2. IPNV Antigen Uptake and Distribution in Atlantic Salmon Following Oral Administration

    Directory of Open Access Journals (Sweden)

    Lihan Chen

    2015-05-01

    Full Text Available One impediment to the successful oral vaccination in fish is the hostile stomach environment that antigens must cross. Furthermore, uptake of antigens from the gut to systemic distribution is required for induction of systemic immunity, the dynamics of which are poorly understood. In the present study, groups of Atlantic salmon parr were intubated with live or inactivated infectious pancreatic necrosis virus (IPNV, either orally or anally. At 1, 24 and 72 h post infection (p.i., the fish were sacrificed. Serum was used for assessing IPNV by ELISA, while formalin-fixed head-kidney, spleen, liver and intestine tissues were used for the demonstration of antigens by immunohistochemistry. Both live and inactivated IPNV antigens were observed in enterocytes of the intestines and in immune cells of the head-kidneys and spleens of all groups. In the liver, no antigens were observed in any of the groups. Significantly higher serum antigen OD values (p < 0.04 were observed in orally- compared to anally-intubated fish. By contrast, no difference (p = 0.05 was observed in tissue antigens between these groups by immunohistochemistry. No significant difference (p = 0.05 in serum antigens was observed between groups intubated with live and inactivated IPNV, while in tissues, significantly more antigens (p < 0.03 were observe in the latter compared to the former. These findings demonstrate that both live and inactivated IPNV are taken up by enterocytes in the intestines of Atlantic salmon, likely by receptor-mediated mechanisms. Higher IPNV uptake by the oral compared to anal route suggests that both the anterior and posterior intestines are important for the uptake of the virus and that IPNV is resistant to gastric degradation of the Atlantic salmon stomach.

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

    OpenAIRE

    Brian Dellavalle; Gitte Stokvad Brix; Birgitte Brock; Michael Gejl; Jørgen Rungby; Agnete Larsen

    2016-01-01

    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 ...

  4. Morphine and Codeine in Oral Fluid after Controlled Poppy Seed Administration

    OpenAIRE

    Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A.; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important drug class in drug testing programs. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only 2 addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine an...

  5. 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.

  6. 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

    , 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...

  7. Systemic immune responses to oral administration of recombinant attenuated Salmonella typhimurium expressing Helicobacter pyloriurease in mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Liu; Jia-Lu Hu; Qi-Zheng Quan; Zi-Qin Sun; Yao-Jun Wang; Feng Qi

    2005-01-01

    AIM: To evaluate whether attenuated Salmonellatyphimurium producing Helicobacter pylori ( H pylori) urease subunit B (UreB) could induce systemic immune responses against H pylori infection.METHODS: Attenuated S. typhimurium SL3261 was used as a live carrier of plasmid pTC01-UreB, which encodes recombinant H pylori UreB protein. Balb/c mice were given oral immunization with two doses of SL3261/pTC01-UreBat a 3-wk interval. Twelve weeks after oral immunization of mice, serum IgG antibodies were evaluated by ELISA assay. Gamma interferon (IFN-γ) and interleukin 10 (IL-10)in the supernatant of spleen cell culture were also assessed by ELISA.RESULTS: After oral immunization of mice, serum specific IgG antibodies against UreB in vaccine group were much higher than that in PBS and native Salmonella SL3261control groups (A450, 0.373±0.100 vs 0.053±0.022, 0.142±0.039, respectively, P<0.01). Moreover, IFN-γ in vaccine group was on average 167.53±29.93 pg/mL, which showed a significant increase vs that of PBS control group (35.68±3.55 pg/mL, P<0.01). There was also a tremendous increase of IL-L0 in vaccine group compared to PBS and SL3261 control groups (275.13±27.65 pg/mL vs 56.00±7.15 pg/mL, 68.02±15.03 pg/mL, respectively, P<0.01). In addition, no obvious side effects in mice and no change in gastric inflammation were observed. CONCLUSION: The multiple oral immunizations with the attenuated S. typhimurium expressing H pylori UreB could induce significant systemic immune responses, suggesting it may be used as oral vaccine against H pylori infection.

  8. Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Nader, Michael A

    2015-03-13

    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

  9. 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.

  10. Pharmacokinetics and Tissue Distribution Study of Chlorogenic Acid from Lonicerae Japonicae Flos Following Oral Administrations in Rats

    Directory of Open Access Journals (Sweden)

    Yulu Zhou

    2014-01-01

    Full Text Available Chlorogenic acid (ChA is proposed as the major bioactive compounds of Lonicerae Japonicae Flos (LJF. Forty-two Wistar rats were randomly divided into seven groups to investigate the pharmacokinetics and tissue distribution of ChA, via oral administration of LJF extract, using ibuprofen as internal standard, employing a high performance liquid chromatography in conjunction with tandem mass spectrometry. Analytes were extracted from plasma samples and tissue homogenate by liquid–liquid extraction with acetonitrile, separated on a C18 column by linear gradient elution, and detected by electrospray ionization mass spectrometry in negative selected multiple reaction monitoring mode. Our results successfully demonstrate that the method has satisfactory selectivity, linearity, extraction recovery, matrix effect, precision, accuracy, and stability. Using noncompartment model to study pharmacokinetics, profile revealed that ChA was rapidly absorbed and eliminated. Tissue study indicated that the highest level was observed in liver, followed by kidney, lung, heart, and spleen. In conclusion, this method was suitable for the study on pharmacokinetics and tissue distribution of ChA after oral administration.

  11. Protection of Macrobrachium rosenbergii against white tail disease by oral administration of bacterial expressed and encapsulated double-stranded RNA.

    Science.gov (United States)

    Naveen Kumar, Singaiah; Karunasagar, Indrani; Karunasagar, Iddya

    2013-09-01

    White tail disease (WTD) of cultured Macrobrachium rosenbergii is caused by M. rosenbergii nodavirus (MrNV) and an extra small virus (XSV), both present together, and the mortality rate can be as high as 100% within 2 or 3 days of infection. Possible protection of M. rosenbergii against WTD by oral administration of bacterial expressed and encapsulated double-stranded RNA (dsRNA) was studied. Juvenile M. rosenbergii were fed with the feed coated with inactivated bacteria encapsulated dsRNA of MrNV and XSV genes individually and in combination for 7 days followed by challenge with WTD causing agents at 24 h and 72 h post-feeding. Test animals fed with a combination of dsRNA of MrNV and XSV capsid genes showed the highest relative percent survival (RPS) when compared to other treatments with RPS of 80% and 75% at 24 and 72 h respectively. One hundred percent mortality was observed in test animals fed with control dsRNA coated feed. Although in the literature, injection is the most common method used to deliver dsRNA, this study shows that oral administration is effective, feasible and economical.

  12. Pharmacokinetic study of p-coumaric acid in mouse after oral administration of extract of Ananas comosus L. leaves.

    Science.gov (United States)

    Meng, Zhen; Wang, Wei; Xing, Dong-Ming; Lei, Fan; Lan, Jia-Qi; Du, Li-Jun

    2006-09-01

    Quantification of p-coumaric acid in mouse plasma following oral administration of Ananas comosus L. leaves was achieved by reversed-phase high-performance liquid chromatography using a mobile phase of water-acetonitrile (82:18, v/v) and UV detection at 310 nm. The method was linear (determination coefficient, r2 = 0.9997) within the tested range (0.04-1.28 microg/mL). Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (maximal CV value was 4.06% for intra-day and 4.19% for inter-day) over the entire range. The recoveries were 90.63, 97.98 and 100.01% for concentrations of 0.04, 0.32 and 1.28 microg/mL, respectively. This is a very rapid, sensitive and economical way to determine p-coumaric acid concentration in mouse plasma after oral administration of A. comosus leaves. The concentration-time curve was fitted to the one-compartment model. This is the first time that p-coumaric acid extracted from A. comosus leaves was detected by HPLC-UV method and its pharmacokinetic characteristic was comprehensively studied.

  13. Tracer kinetics and actions of oral and intraperitoneal 1,25-dihydroxyvitamin D3 administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, R.; Kooh, S.W.; Balfe, J.W.; Rawlins, M.; Tinmouth, W.W. (Univ. of Toronto, Ontario (Canada))

    1990-11-01

    Tracer kinetic parameters of ({sup 3}H)-1,25(OH)2D3 were calculated from data obtained following its acute oral (p.o.) or intraperitoneal (i.p.) administration. In normal rats studied after the tracer had distributed into the body, the slope and intercept of the log-serum ({sup 3}H)-1,25(OH)2D3 versus time relationship were not significantly influenced by the route of administration. Pretreatment with 1,25(OH)2D3 (0.2 micrograms/100 g/day) by the same route as the tracer resulted in the following changes: in p.o. rats the serum ({sup 3}H)-1,25(OH)2D3 intercept was much lower but the slope was not changed; in i.p. rats the intercept was not changed but the slope was increased. Both p.o. and i.p. treatment with 1,25(OH)2D3 lowered the weight gain and diet consumption, and increased serum calcium, kidney tissue calcium and urinary excretion of orally administered {sup 45}Ca. All the measures of bioactivity were greater in the i.p. dosed rats than in the p.o. dosed rats. We conclude that the p.o. 1,25(OH)2D3 was less potent because of diminished bioavailability due to self induction of its presystemic metabolism and inactivation.

  14. The application of Traditional Chinese Drugs(TCD) by Non- oral Gastrointestinal Administration in Complicated and Serious Diseases

    Institute of Scientific and Technical Information of China (English)

    HE Lirong; HE Gang

    2002-01-01

    Objective To discuss the curative efficacy of TCD compounds by non- oral gastrointestinal administration in order to solve the problem on dosage forms of TCD in rescue of complicated and serious diseases. Method Gastric tube perfusion or retention enema or drainage tube was applied for theadministration of TCD decoctions, pills or powders. Results In rescuing MOF patients with intestinal paralysis after cesarean section due to retained stillbirth who got no effect by gastrointestinal decompression and anal exsufflation for 48 hours, they were survived after gastric tube perfusion of JiaWei HuangLong Decoction. In dying patients with shock due to poisoned bacterial dysentery, they were saved after retention enema of AnGong NiuHuang Pill. In infants with fever due to sporadic encephalitis who got convulsion, trismus and drank no water, their convulsions disappeared overnight after retention enema of AnGong NiuHuang Pill plus cornu saigae tataricae powder. Conclusion It has been showed that under present situation that TCD injections couldn' t meet the need of complicated and serious diseases, the application of TCD by non - oral gastrointestinal administration in rescuing complicated and serious diseases was an effective emergency measure.

  15. 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...

  16. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem.

    Science.gov (United States)

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-05-01

    Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C max, T max, and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F a_IO). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R (2) > 0.9). The predicted deviations (%) for C max, AUC0-inf, AUC0-20 min, and T max were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated ~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F a_IO was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f ut) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD pH = 7.4). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations.

  17. [Expression of human insulin in lactic acid bacteria and its oral administration in non-obese diabetic mice].

    Science.gov (United States)

    Chen, Si-Wei; Zhong, Jin; Huan, Lian-Dong

    2007-12-01

    Type 1 diabetes mellitus (T1DM) is an auto-immune disease while oral administrating its autoantigens could be a treatment of T1DM. To express human insulin gene (ins) in lactic acid bacteria (LAB) for oral vaccine, ins gene was replaced by LAB bias codon and an 8-amino-acid-residue linker peptide forming a beta-turn was designed to link insulin chain A and B. After synthesized by primer annealing method, the whole ins gene was fused with signal peptide sequence SP(Usp45), subcloned into a LAB secretory expressive vector pSW501 and then introduced to Lactococcus lactis (L. lactis) MG1363 and Lactobacillus casei (Lb. casei ) ATCC27092 respectively. Western blot showed that the expression product (SP(Usp45)-INS protein) targeted mainly at the cell wall while little was found in cytoplasm or supernatant. The highest expression level emerged in exponential phase when the optical density at 600nm of the culture was 0.4. The culture of the recombinant strain Lb. casei/pSW501 was administered to non-obese diabetic (NOD) mice orally. ELISA and Western blot results showed that the recombinant strain could induce SP(Usp45)-INS-specific antibodies and raise IL-4 level (38.583 +/- 2.083 pg/mL, P < 0.05) in the mice' s sera. Expression of insulin in the food-grade vehicle LAB could induce oral immune tolerance in NOD mice and protect it from pancreas injury, suggesting it might be a new way to the treatment of T1DM.

  18. Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study.

    Science.gov (United States)

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

    2015-05-01

    N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors.

  19. 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.

  20. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.

    Science.gov (United States)

    Sattar, Adeel; Xie, Shuyu; Huang, Lingli; Iqbal, Zahid; Qu, Wei; Shabbir, Muhammad A; Pan, Yuanhu; Hussain, Hafiz I; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Iqbal, Mujahid; Yuan, Zonghui

    2016-01-01

    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.

  1. Effects of somatostatin and oral potassium administration on terbutaline-induced hypokalemia.

    Science.gov (United States)

    Schnack, C; Podolsky, A; Watzke, H; Schernthaner, G; Burghuber, O C

    1989-01-01

    Terbutaline, a beta 2-adrenergic agonist, has been shown to cause hypokalemia and an increase of plasma glucose and serum insulin concentrations. We considered that terbutaline-induced hypokalemia may be due to the insulin-induced shift of potassium (K+) from the extracellular to the intracellular space. If so, then inhibition of insulin secretion by somatostatin would prevent terbutaline-induced hypokalemia. Further, we wondered whether oral potassium pretreatment could prevent terbutaline-induced hypokalemia. Therefore, 10 healthy volunteers (5 men, 5 women; mean age, 23 yr +/- 3 SD) received either sodium chloride (NaCl) or somatostatin intravenously together with 0.25 mg terbutaline subcutaneously in a double-blind crossover design. On a third test day, they received 39 mval of K+ powder orally before terbutaline injection in an open trial. Terbutaline caused a significant decrease of K+ (from 3.96 +/- 0.08 to 3.3 +/- 0.13 mmol/L +/- SEM; p less than 0.0005), accompanied by a significant increase in plasma glucose (from 83 +/- 3.6 to 101 +/- 4.4 mg/dl +/- SEM; p less than 0.01) and serum insulin concentrations (from 11.7 +/- 0.9 to 19.9 +/- 1.1 microU/ml +/- SEM; p less than 0.001), confirming earlier data. Somatostatin pretreatment inhibited the terbutaline-induced hypokalemia; the small fall of K+ (from 3.7 +/- 0.08 to 3.5 +/- 0.2 mmol/L) was no longer significant. Insulin secretion was completely blocked by somatostatin, leading to an even more pronounced increase of blood glucose. Hypokalemia after terbutaline injection was not prevented by oral potassium pretreatment. In summary, the present findings confirm that terbutaline-induced hypokalemia is associated with increased plasma glucose and insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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

    Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin...... 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...

  3. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

    Directory of Open Access Journals (Sweden)

    Martín-Moreno Ana María

    2012-01-01

    Full Text Available Abstract Background Alzheimer's disease (AD brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. Methods We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG uptake by positron emission tomography (PET. Results Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. Conclusions In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.

  4. 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)

  5. Preparation and characterization of novel fast disintegrating capsules (Fastcaps) for administration in the oral cavity.

    Science.gov (United States)

    Ciper, Mesut; Bodmeier, Roland

    2005-10-13

    The objective of this study was to prepare novel capsule-based fast disintegrating dosage forms for the oral cavity (Fastcaps). First, cast films were prepared from various additive-containing gelatin solutions and evaluated with respect to disintegration time and mechanical properties in order to identify suitable formulations for the capsule preparation. The disintegration time of films decreased with decreasing bloom strength and could be further decreased by the addition of sugars or PEGs. Fast disintegrating capsules were successfully prepared by a dipping process, whereby parameters such as the viscosity and temperature of the dipping solution and the dipping velocity of the steel pins were optimized. The required viscosity range of the dipping solution for Fastcap manufacturing was 500-600 cP. The addition of the hydrophilic additives (xylitol, sorbitol or PEG 1500) did not significantly affect the viscosity and gelation temperature of the dipping solution. The in vitro disintegration of Fastcaps (30-45 s) was twice as rapid as the one of regular hard gelatin capsules. In vivo, Fastcaps disintegrated rapidly (9-13 s) and their content was spread throughout the oral cavity within seconds. Lactose and/or microcrystalline cellulose were suitable fillers for Fastcaps. The mechanical properties of Fastcaps were similar to commercially available gelatin capsules, which assures good processability and handling.

  6. A ceramic drug delivery vehicle for oral administration of highly potent opioids.

    Science.gov (United States)

    Forsgren, Johan; Jämstorp, Erik; Bredenberg, Susanne; Engqvist, Håkan; Strømme, Maria

    2010-01-01

    Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

  7. Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A

    2002-07-01

    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 {sup 10}B(n,a){sup 7}Li reaction products is very short, 10-14 {mu}m 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 {sup 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 {sup 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)

  8. Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: a novel strategy to avoid intraduodenal administration.

    Science.gov (United States)

    Venishetty, Vinay Kumar; Chede, Raghavendra; Komuravelli, Rojarani; Adepu, Laxminarayana; Sistla, Ramakrishna; Diwan, Prakash V

    2012-06-15

    Solid lipid nanoparticles are most promising delivery systems for the enhancement of bioavailability of highly lipophilic drugs those prone to the first pass metabolism. But burst release of drug from solid lipid nanoparticles in acidic environment such as gastric milieu precludes its usage as oral delivery system. Studies on SLN revealed intraduodenal administration as an alternative route for SLN administration. But clinically it is an inappropriate route for repeated administration of drugs to patients. Hence, we prepared N-carboxymethyl chitosan (MCC) coated carvedilol loaded SLN to protect the rapid release of carvedilol in acidic environment. Positively charged carvedilol loaded SLN were developed using monoglyceride as lipid and soya lecithin and poloxamer 188 as surfactants and stearylamine as charge modifier. These SLN were characterized for particle size, zeta potential, entrapment efficiency, crystallinity and stability studies. Further these SLN were coated with N-carboxymethyl chitosan and confirmed by change in zetapotential and X-ray Photon Spectroscopic analysis. Effect of polymer coating on drug release profiles were studied simulated gastric and intestinal fluids. Effect of polymer coating on oral bioavailability of carvedilol loaded SLN were studied in rats after oral administration. MCC coated SLN improved the bioavailability of carvedilol compared uncoated SLN after oral administration. Insignificant difference in bioavailability was observed compared to intraduodenal administration of SLN. Hence, MCC coated SLN is a novel strategy to avoid intrduodenal administration.

  9. The effect of timing of oral meloxicam administration on physiological responses in calves after cautery dehorning with local anesthesia.

    Science.gov (United States)

    Allen, K A; Coetzee, J F; Edwards-Callaway, L N; Glynn, H; Dockweiler, J; KuKanich, B; Lin, H; Wang, C; Fraccaro, E; Jones, M; Bergamasco, L

    2013-08-01

    Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28-70 kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E2 (PgE2) production after lipopolysaccharide stimulation and meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14 μg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26 h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in meloxicam-treated calves compared with control calves at 4 h postdehorning. Substance P concentrations were significantly higher in control calves compared with meloxicam-treated calves at 120 h after dehorning. Prostaglandin E2 concentrations were lower in meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin

  10. Pharmacokinetics of the individual enantiomer S-(+)-ketoprofen after intravenous and oral administration in dogs at two dose levels.

    Science.gov (United States)

    Serrano-Rodríguez, J M; Serrano, J M; Rodríguez, J Morgaz; Machuca, M M Granados; Gómez-Villamandos, R J; Navarrete-Calvo, R

    2014-06-01

    The pharmacokinetic of the individual S-(+)-enantiomer of ketoprofen, S-(+)-ketoprofen, after intravenous (IV) and oral (PO) administration was determined in six dogs at 1 and 3 mg/kg. Plasma concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time curves were analyzed by non-compartmental methods. Steady-state volume of distribution (Vss) and clearance (Cl) of S-(+)-ketoprofen after IV administration were 0.22 ± 0.07 and 0.19 ± 0.03 L/kg, and 0.10 ± 0.02 and 0.09 ± 0.01 L/h/kg, at 1 and 3 mg/kg, respectively. Following PO administration, S-(+)-ketoprofen achieved maximum plasma concentrations of 4.91 ± 0.76 and 12.47 ± 0.62 μg/ml, at two dose levels, respectively. The absolute bioavailability after PO route was 88.66 ± 12.95% and 85.36 ± 13.90%, respectively.

  11. Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis.

    Science.gov (United States)

    Deventer, K; Pozo, O J; Van Eenoo, P; Delbeke, F T

    2009-03-20

    In sports, thiazide diuretics are used to flush out previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. Thiazide diuretics include compounds which are very unstable and hydrolyse in aqueous media. Because information regarding the urinary detection of the hydrolysis products is limited, urinary excretion profiles for the hydrolysis product 4-amino-6-chloro-1,3-benzenedisulphonamide were established in 6 healthy volunteers after oral administration of altizide (15 mg per tablet) and hydrochlorothiazide (25mg per tablet). Additionally, the excretion profile of chlorothiazide, a metabolite of altizide and hydrochlorothiazide, was also determined. A quantitative liquid-chromatographic tandem mass spectrometric method to detect the 4 substances was developed and validated. The result of this work shows that altizide is eliminated within 48 h in urine whereas hydrochlorothiazide was detectable after 120 h. Chlorothiazide was determined to be a minor metabolite of altizide and hydrochlorothiazide and could be detected up to 120 h. The hydrolysis product, 4-amino-6-chloro-1,3-benzenedisulphonamide, was detectable 120 h after administration, with concentrations at least 10 times higher than the parent drug. Concentrations ranged between 41-239 and 60-287 ng/mL after altizide and hydrochlorothiazide administration, respectively. The study shows that 4-amino-6-chloro-1,3-benzenedisulphonamide is an important target compound for the long time detection of thiazide diuretics in urine.

  12. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

    Science.gov (United States)

    Iida, Tetsuo; Kishimoto, Yuka; Yoshikawa, Yuko; Hayashi, Noriko; Okuma, Kazuhiro; Tohi, Mikiko; Yagi, Kanako; Matsuo, Tatsuhiro; Izumori, Ken

    2008-12-01

    An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

  13. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Ding

    2014-01-01

    Full Text Available Previous studies reported the oral administration of Naja naja atra venom (NNAV reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  14. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

    Science.gov (United States)

    Ding, Zhi-Hui; Xu, Li-Min; Wang, Shu-Zhi; Kou, Jian-Qun; Xu, Yin-Li; Chen, Cao-Xin; Yu, Hong-Pei; Qin, Zheng-Hong; Xie, Yan

    2014-01-01

    Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180  μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  15. Time course of arsenic species in the brain and liver of mice after oral administration of arsenate

    Energy Technology Data Exchange (ETDEWEB)

    Juarez-Reyes, Amida; Jimenez-Capdeville, Maria E.; Delgado, Juan M.; Ortiz-Perez, Deogracias [Universidad Autonoma de San Luis Potosi, Departamento de Bioquimica, Facultad de Medicina, San Luis Potosi (Mexico)

    2009-06-15

    The understanding of the biomethylation process of arsenic is essential to uncover the mechanisms of arsenic toxicity. This work analyzes the time course of arsenic species in the brain and liver of adult mice, after a single oral administration of three arsenate doses [2.5, 5.0 and 10 mg As(V)/kg]. Quantification of arsenic species was performed by means of liquid chromatography coupled to atomic fluorescence 2, 5, 8, 12 and 24 h after administration. The results show that 2 h after arsenate administration inorganic arsenic arrives to the liver and its concentration diminishes gradually until becoming non-detectable at 12 h. Arsenic takes longer to appear in the brain and it is present only as dimethyl arsinic acid. Since arsenic concentration decreases in liver while it increases in the brain, this suggests that the arsenic metabolite reaches the brain after formation in the liver. Importantly, the fact that dimethyl arsinic acid is no longer present after 24 h suggests the existence of a mechanism to clear this metabolite from brain tissue. (orig.)

  16. The effect of oral administration of Withania somnifera root on formalin-induced pain in diabetic rats

    Directory of Open Access Journals (Sweden)

    Mohsen Khalili

    2009-01-01

    Full Text Available   Abstract  Introduction: Hyperalgesia is considered as one the marked signs of subchronic diabetes mellitus that could affect the life style of the patients. With c onsidering the potential anti-diabetic effect of the medicinal plant Withania somnifera (WS( ashwagandha, this study was designed to investigate the analgesic effect of WS on formalin-induced nociceptive responses (standard formalin test in diabetic rats. Methods: Rats were divided into control, WS-treated control, diabetic, sodium salicylate (SS-treated control and diabetic and WS-treated diabetic groups. For induction of diabetes, streptozotocin (STZ was used at a single dose. The treatment groups received oral administration of ashwagandha -mixed rat pellet (6.25% for two months.  Results: The results showed that diabetic rats exhibited a higher score of pain at both phases of the formalin test and WS-treated diabetic rats exhibited a lower nociceptive score at both phases of the test (p<0.05. Meanwhile, SS administration significantly reduced pain score only at chronic phase of the test in the diabetic group (p<0.01.   Discussion: Taken together, these results indicate that two-month administration of ashwagandha could attenuate nociceptive score in an experimental model of diabetes mellitus and this may be considered as a potential treatment for painful diabetic neuropathy.  

  17. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

    Science.gov (United States)

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer

    2003-02-01

    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  18. Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration.

    Science.gov (United States)

    Agarwal, Vikas; Alayoubi, Alaadin; Siddiqui, Akhtar; Nazzal, Sami

    2013-11-01

    The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. meloxicam and meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.

  19. In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy adult mice.

    Science.gov (United States)

    Hassankhani, Ramin; Esmaeillou, Mohammad; Tehrani, Ali Asghar; Nasirzadeh, Keyvan; Khadir, Fatemeh; Maadi, Hamid

    2015-01-01

    The increasing use of silica nanoparticles (SiNPs) in various applications including industrial, agriculture, and medicine has raised concerns about their potential risks to human health. Various nanotoxicity researches have been done on the assessment of SiNPs' toxic effects; however, a few in vivo investigations exist. In this investigation, an in vivo study was done in order to evaluate the oral toxicity of SiNPs. The biochemical levels of 19 different serum parameters were assessed. Moreover, the histopathological changes have been examined as well. We showed that SiNPs with diameters of 10-15 nm in size can cause significant changes in albumin, cholesterol, triglyceride, total protein, urea, HDL, and LDL as well as in alkaline phosphatase and aspartate aminotransferase activity. In addition, histopathological examinations demonstrated that SiNPs have toxic effects on various tissues including liver, kidney, lung, and testis.

  20. Oral health knowledge and practice among administrative staff at Taibah university, Madina, KSA

    Directory of Open Access Journals (Sweden)

    Mohammad Sami Ahmad

    2013-01-01

    Full Text Available Background: Although the prevalence of dental caries is decreasing in developed countries, it is still increasing in developing countries. No studies have reported on the oral health status of adults in Saudi Arabia; the role models and parents for the younger generation. Materials and Methods: This was a cross-sectional study carried out between January and June 2012 and included 200 randomly chosen Taibah university staff members. Each participant received a self-administered questionnaire and consent form detailing the objectives and rational of the study. Results: The response rate was 74%; mean age was 32.6 years and almost 90% had obtained higher educational qualifications. Nearly, half (48% cleaned their teeth in the morning and evening, 77% used a tooth stick and toothbrush and almost 90% used tooth paste regularly. Under two-thirds (61% visited the Dentist only when necessary and 13% had never visited a Dentist. The treatment received included restorations (35%, scaling and polishing (21% and extractions (18%. Of those who did not visit the Dentist, 40% cited the high cost as the reason. The majority (78% were aware that sugar is harmful for the teeth. Under half (46% used tobacco and 36% had medical conditions. Those who visited the Dentist were more likely to brush twice daily (P=0.04 and of those who brushed regularly, 50% knew the number of permanent teeth present (P=0.04 and 57% were aware of the benefits of fluoride (P=0.01. Conclusion: The majority of respondents had a poor level of knowledge regarding oral hygiene. This was reflected in their poor and inconsistent brushing habits and their lack of utilization of dental services.

  1. 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.

  2. Different Kinetics of Puerarin in Plasma of Normal and Depressed Rats After Oral Administration of Chinese Medicine TZ18

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The objective of this study is to quantify the puerarin in rat plasma following oral administration of TZ18 and compare the pharmacokinetics characteristics of puerarin in normal rats with that in depression model rats. A high performance liquid chromatography method was used to quantify the puerarin due to its Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (Maximum coefficient of variation was 5.74% for intra-day and 3.09% for inter-day) over the entire range. The recoveries spectively. The concentration-time curves for both normal rats and depression model rats were fit to a twocompartment model with the first order absorption. The results show significant differences in the main pharmacokinetic parameters of peak time, peak concentration, and the area under the concentration-time curve between the two kinds of rats.

  3. Pharmacokinetic Profile of Eight Phenolic Compounds and Their Conjugated Metabolites after Oral Administration of Rhus verniciflua Extracts in Rats.

    Science.gov (United States)

    Jin, Ming Ji; Kim, In Sook; Park, Jong Suk; Dong, Mi-Sook; Na, Chun-Soo; Yoo, Hye Hyun

    2015-06-10

    Rhus verniciflua (Toxicodendron vernicifluum) is a medicinal tree popularly used in Asian countries such as China, Japan, and Korea as a food additive or herbal medicine because of its beneficial effects. R. verniciflua extract (RVE) contains diverse phenolic compounds, such as flavonoids, as its major biological active constituents. In this study, the pharmacokinetic profiles of eight phenolic compounds were investigated following oral administration of RVE to rats. The eight phenolic compounds were 2,4-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, fisetin, fustin, butin, sulfuretin, taxifolin, and garbanzol. The plasma concentrations of the eight compounds were determined by using a liquid chromatography-triple-quadrupole mass spectrometer before and after treatment with β-glucuronidase. When 1.5 g/kg RVE was administered, the eight compounds were all detected in plasma, mainly as conjugated forms. These pharmacokinetic data would be useful for understanding the pharmacological effects of RVE.

  4. DNA damage detected by the alkaline comet assay in the liver of mice after oral administration of tetrachloroethylene.

    Science.gov (United States)

    Cederberg, Håkan; Henriksson, Jörgen; Binderup, Mona-Lise

    2010-03-01

    Induction of DNA damage in the liver and kidney of male CD1 mice was studied by means of the alkaline Comet assay after oral administration of tetrachloroethylene at the doses of 1000 and 2000 mg/kg/day. A statistically significant dose-related increase in tail intensity was established in hepatocytes, indicating that tetrachloroethylene induced DNA damage in the liver. No effect on DNA damage was observed in the kidney. The results are in agreement with carcinogenicity data in mice, in which tetrachloroethylene induced tumours in the liver but not in the kidney, and support that a genotoxic mode of action might be involved in liver carcinogenicity in mice. An alternative interpretation of the results conveyed by the Study director at the test facility, involving that tetrachloroethylene did not induce DNA damage in the liver and kidney of mice, is also presented and discussed.

  5. 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.

  6. Protection against atypical Aeromonas salmonicida infection in carp (Cyprinus carpio L.) by oral administration of humus extract.

    Science.gov (United States)

    Kodama, Hiroshi; Denso; Nakagawa, Tsuyoshi

    2007-04-01

    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms have been present. In the present study, oral administration of humus extract to common carp (Cyprinus carpio L.) induced effective protection against experimental atypical Aeromonas salmonicida infection. Mortality of fish and development of skin lesions such as hemorrhages and ulcers were significantly suppressed in carp treated with 10%, 5% or 1% humus extract adsorbed on dry feeding pellets. The median surviving days was also greater in fish treated with 10% or 5% humus extract than in untreated fish. Atypical A. salmonicida was isolated from ulcerative lesions of part of dead fish, but Aeromonas hydrophila and Flavobacterium sp. were also isolated from these fish, verifying bacterial population changes during the progression of skin lesions. These results clearly show that treatment of fish with humus extract is effective in preventing A. salmonicida disease.

  7. [Injury and reparative regeneration of the oral mucosal epithelium after cytostatic drugs administration (tissue, cell and molecular mechanisms)].

    Science.gov (United States)

    Bykov, V L; Leont'eva, I V

    2011-01-01

    This paper presents the systematized summary of current literature data and the authors' own findings on the regularities of human and animal surface oral mucosal epithelium (OME) injury caused by cytostatic drugs (CSD) administration, and on the ways of its regeneration after the cytostatic chemotherapy (CSCT) discontinuation. Tissue, cell and molecular mechanisms of CSCT effects on OME, are described. The direct effects of CSD included the epithelial layer attenuation with the derangement of its architecture, epitheliocyte proliferation suppression, apoptosis activation, and differentiation disturbances (involving the broad spectrum of cytological, cytochemical, ultrastructural and molecular-biological changes). In severe cases, these processes resulted in the loss of the epithelial layer integrity with the development of ulceration. Complete epithelial regeneration requires a long period after the CSCT discontinuation. Indirect effects of CSD on OME are associated with the microbial invasion and the diffusion of microbial vital activity products into the epithelium with concurrent leukopenia, immunosuppression and decreased salivary secretion.

  8. Comparative Pharmacokinetics of Naringin in Rat after Oral Administration of Chaihu-Shu-Gan-San Aqueous Extract and Naringin Alone

    Directory of Open Access Journals (Sweden)

    Hong-Wu Zhang

    2013-09-01

    Full Text Available Chaihu-Shu-Gan-San (CSGS, a traditional Chinese medicine (TCM formula containing seven herbal medicines, has been used in the clinical treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression in China. In order to explore the interaction between naringin and other constituents in CSGS, the pharmacokinetic difference of naringin in rats after oral administration of CSGS aqueous extract and naringin alone was investigated. The pharmacokinetic parameters of naringin in rats were achieved by quantification of its aglycone, naringenin by LC-MS/MS method. The double peaks phenomenon was observed in both serum profiles of rats after orally administered CSGS aqueous extract and naringin alone. However, the T1/2b was significantly decreased in rats given CSGS aqueous extract compared with naringin alone, and the mean residence time (MRT and the area under the serum concentration–time curve (AUC0-τ were higher than those of naringin, which indicated that naringin in CSGS had higher bioavailability, longer term efficacy and somewhat faster metabolism and excretion than those of naringin. The results suggested that certain ingredients co-exist in CSGS could influence pharmacokinetic behavior of naringin. This also provides a reference for human studies.

  9. 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.

  10. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration.

    Science.gov (United States)

    Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-10-01

    The present study reports the tetanus toxoid (TT)-loaded layer-by-layer nanoassemblies (layersomes) with enhanced protection, permeation, and presentation for comprehensive oral immunization. The stable and lyophilized TT-loaded layersomes were prepared by a thin-film hydration method followed by alternate layer-by-layer coating of an electrolyte. The developed system was assessed for in vitro stability of antigen and formulation, cellular uptake, ex vivo intestinal uptake, and immunostimulatory response using a suitable experimental protocol. Layersomes improved the stability in simulated biological media as well as protected the integrity/conformation and native 3D structure of TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW 264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and cellular (interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels) immune response after peroral administration in mice. The modified TT inhibition assay further confirmed the elicitation of complete protective levels of anti-TT antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is expected to contribute significantly in the field of stable liposome technology for mass immunization through the oral route.

  11. Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol.

    Science.gov (United States)

    García Quetglas, Emilio; Azanza, Jose Ramón; Cardenas, Ernesto; Sádaba, Belén; Campanero, Miguel Angel

    2007-01-01

    The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O-demethyltramadol and N-demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O-demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N-demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(-)-tramadol. The formation of N-demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)-N-demethyltramadol than for (S)-(-)-N-demethyltramadol. In the opposite form, (S)-(-)-O-demethyltramadol was formed faster than (R)-(+)-O-demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N-demethyltramadol was concentration-dependent.

  12. Antimicrobial peptide CAP18 and its effect on Yersinia ruckeri infections in rainbow trout Oncorhynchus mykiss (Walbaum): comparing administration by injection and oral routes.

    Science.gov (United States)

    Chettri, J K; Mehrdana, F; Hansen, E B; Ebbensgaard, A; Overgaard, M T; Lauritsen, A H; Dalsgaard, I; Buchmann, K

    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 disease caused by this pathogen either following i.p. injection or by oral administration (in feed). It was found that injection of CAP18 into juvenile rainbow trout before exposure to Y. ruckeri was associated with lowered mortality compared to non-medicated fish although it was less effective than 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.

  13. The metabolic disposition of /sup 14/C-labelled carmoisine in the rat after oral and intravenous administration

    Energy Technology Data Exchange (ETDEWEB)

    Galli, C.L.; Marinovich, M.; Costa, L.G.

    1982-08-01

    The absorption, distribution and excretion of the red azo dye carmoisine (Ext. D and C No. 10) was studied in male rats. (/sup 14/C)Carmoisine was administered in a dose of 200 mg/kg (25 microCi) by gavage or in the same dose (200 mg/kg; 3 microCi) by intravenous injection, and radioactivity was measured in blood, tissue, faeces and urine at different times after dosing. After oral administration of the dye, no radioactivity was detected in the brain, adipose tissue, muscle, testes, spleen or lung, and recovery of the administered activity in faeces and urine was almost complete by 32 hr. The radioactivity profile of the blood indicated rapid but poor absorption of (/sup 14/C)carmoisine, a maximum radioactivity content corresponding to 0.01% of the dose per ml of blood being reached within 10 min. The decay curve for /sup 14/C radioactivity in the blood after iv injection of (/sup 14/C)carmoisine indicated rapid distribution to the tissues and could be described in terms of a two-compartment mathematical model. The highest levels of radioactivity occurred in the gastro-intestinal tract and liver after the injection but after 24 hr no radioactivity was detectable in these or other tissues. All the radioactivity was recovered in the faeces and urine in the 24 hr following iv injection, the 79% of the dose present in faeces indicating active excretion of the dye and its metabolites in the bile and poor reabsorption from the intestine. The bioavailability of (/sup 14/C)carmoisine, calculated from the blood-radioactivity curves after oral and iv administration, was less than 10%.

  14. Effects of Chronic Oral Administration of Natural Honey on Ischemia/Reperfusion-induced Arrhythmias in Isolated Rat Heart

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    Moslem Najafi

    2011-01-01

    Full Text Available Objective(sIn this study, effects of chronic administration of oral natural honey against ischemia/reperfusion (I/R-induced cardiac arrhythmias were investigated in isolated rat heart. Materials and MethodsMale Wistar rats were divided into four groups (n= 10-14 rats in each group and fed with natural honey (1%, 2% and 4% dissolved in the drinking water for 45 days except for the control group. After anesthesia, the rats’ hearts were isolated quickly, mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during stabilization, 30 min regional ischemia followed by 30 min reperfusion. The ECGs were recorded throughout the experiments to analyze cardiac arrhythmias based on the Lambeth conventions. ResultsIn the ischemic phase, honey (1% significantly reduced (P<0.05 the number and duration of ventricular tachycardia (VT. Honey (1% and 2% also significantly decreased number of ventricular ectopic beats (VEBs. In addition, incidence and duration of reversible ventricular fibrillation (Rev VF were lowered by honey 2% (P<0.05. During reperfusion time, VT incidence was 73% in the control group, however natural honey (1% decreased it to 22% (P<0.05. Honey also produced significant reduction in the incidences of total VF, Rev VF, duration and number of VT. ConclusionFor the first time, the results of present study demonstrated protective effects of chronic oral honey administration against I/R-induced arrhythmias in isolated rat heart. Antioxidant activity, the existence of energy sources such as glucose and fructose and improvement of some hemodynamic functions might be responsible for these effects.

  15. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats

    Science.gov (United States)

    Rodrigues, Hosana G.; Vinolo, Marco A. R.; Sato, Fabio T.; Magdalon, Juliana; Kuhl, Carolina M. C.; Yamagata, Ana S.; Pessoa, Ana Flávia M.; Malheiros, Gabriella; dos Santos, Marinilce F.; Lima, Camila; Farsky, Sandra H.; Camara, Niels O. S.; Williner, Maria R.; Bernal, Claudio A.; Calder, Philip C.; Curi, Rui

    2016-01-01

    Introduction Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. Objectives We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. Methods Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. Results LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). Conclusions Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis. PMID:27764229

  16. The assessment of tolerability of prolonged oral eugenol administration in rats

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    Jezdimirović Milanka

    2012-01-01

    Full Text Available The potential toxicity and general tolerability of eugenol following two-week or four-week continuous p.o. administration to rats has been investigated. An experiment was performed on 72 male rats of the Wistar strain. Four groups of rats were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg, 200 mg/kg and 400 mg/kg bm/day, the fifth group was administered vehicle (0.5 % methylcellulose, propylene glycol and water, and the sixth group comprised absolutely untreated controls. The corresponding doses of eugenol and vehicle were applied using a gastric probe in a volume of 1 ml/100 g body mass. The general tolerability of eugenol was evaluated on the basis of the daily intake of water and food, body mass, general health condition, behaviour, and lethality in the course of the experiment. In the investigated doses, eugenol applied p.o. in the course of two or four weeks does not influence significantly the intake of food, water, or body mass of rats. The dose of 400 mg/kg/day produced undesired reactions (agitation and hyperesthesia that were first observed on day 21 and lasted until the end of the experiment. Low subacute toxicity of eugenol was established following p.o. administration to rats. Eugenol in doses of 200 and 400 mg/kg tm/day has a low toxic potential and is safe for administration to this animal species. [Projekat Ministarstva nauke Republike Srbije, br. 46009

  17. Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

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    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.

  18. Contrasting nephropathic responses to oral administration of extract of cultured Penicillium polonicum in rat and primate.

    Science.gov (United States)

    Mantle, Peter G; McHugh, Katharine M; Fincham, John E

    2010-08-01

    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.

  19. Reproducibility of neutron activated Sm-153 oral dose formulations intended for human administration

    Energy Technology Data Exchange (ETDEWEB)

    Yeong, C.H. [Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Blackshaw, P.E. [Medical Physics and Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH (United Kingdom); Ng, K.H.; Abdullah, B.J.J. [Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Blaauw, M. [Reactor Institute Delft, Faculty of Applied Sciences, Delft University of Technology, 2628 CJ Delft (Netherlands); Dansereau, R.J. [Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Rd, Mason (United States); Perkins, A.C., E-mail: alan.perkins@nottingham.ac.uk [Medical Physics and Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH (United Kingdom); Radiological and Imaging Sciences and Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham NG7 2UH (United Kingdom)

    2011-09-15

    Neutron activation of Sm-152 offers a method of radiolabeling for the in vivo study of oral dose formulations by gamma scintigraphy. Reproducibility measurements are needed to ensure the robustness of clinical studies. 204 enteric-coated guaifenesin core tablets (10 mg of Sm{sub 2}O{sub 3}) were irradiated by thermal neutrons to achieve 1 MBq at 48 h. Administered activities were 0.86{+-}0.03 MBq. Good reproducibility (CV=3.5%) was observed over 24 weeks ensuring that volunteer doses were within the dose reference level of 0.8 mSv. - Highlights: > 204 enteric-coated guaifenesin core tablets were irradiated by thermal neutrons. > Activity measured at 48 h after irradiation was 1.01{+-}0.03 MBq. > Activity administered per subject was 0.88{+-}0.03 MBq. > Good reproducibility (CV=3.5%) of Sm-153 radioactivity was obtained. > Effective doses to volunteers were within dose reference level of 0.8 mSv.

  20. 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.

  1. Thymoquinone ameliorates testicular tissue inflammation induced by chronic administration of oral sodium nitrite.

    Science.gov (United States)

    Alyoussef, A; Al-Gayyar, M M H

    2016-06-01

    Although sodium nitrite has been widely used as food preservative, building bases of scientific evidence about nitrite continues to oppose the general safety in human health. Moreover, thymoquinone (TQ) has therapeutic potential as antioxidant, anti-inflammatory, antibacterial and anticancer. Therefore, we investigated the effects of both sodium nitrite and TQ on testicular tissues of rats. Forty adult male Sprague Dawley rats were used. They received either 80 mg kg(-1) sodium nitrite or 50 mg kg(-1) TQ daily for twelve weeks. Serum testosterone was measured. Testis were weighed and the testicular tissue homogenates were used for measurements of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL10, caspase-3, caspase-8 and caspase-9. Sodium nitrite resulted in significant reduction in serum testosterone concentration and elevation in testis weight and Gonado-Somatic Index. We found significant reduction in testicular tissues levels of IL-4 and IL-10 associated with elevated levels of TNF-α, IL-1β, IL-6, caspase-3, caspase-8 and caspase-9. In conclusion, chronic oral sodium nitrite induced changes in the weight of rat testis accompanied by elevation in the testicular tissue level of oxidative stress markers and inflammatory cytokines. TQ attenuated sodium nitrite-induced testicular tissue damage through blocking oxidative stress, restoration of normal inflammatory cytokines balance and blocking of apoptosis.

  2. Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years.

    Science.gov (United States)

    Balan, Guhan; Thompson, Gary A; Gibb, Roger; Li, Lijuan; Hull, David; Seeck, Molly

    2013-11-01

    To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2-17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non-compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P-value = 0.0517). As expected due to increasing body size, CLo and Vz /F increased with age. Due to a similar increase with age for Clo and Vz /F, no age-related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo ; although Vz /F remained age-dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax , whereas AUC increases only 60%.

  3. [Fixed pigmented erythema related to the oral administration of carbamazepine: report of one case].

    Science.gov (United States)

    Alvarez, Verónica J; Picón, Jesús E; Morales, Alexis R; Goncalves, Edith T; Luna, José Rafael

    2006-03-01

    Carbamazepine (CBZ) is an oral anticonvulsant drug, structurally similar to tricyclic antidepressants. It is preferred over other drugs because it has fewer adverse effects on behavior and alertness. However, hematologic toxicity is possible during therapy with CBZ. Patients should undergo routine monitoring of hematologic function. CBZ can make the skin more sensitive to the sun or ultraviolet light, therefore, dermatological effects of this drug also can happen such as, skin rash, urticaria, and erythema multiforme. The present study reports the case of a female patient that presented hyperchromic-concentric-pruriginous- spots on the skin of her hands after six months of treatment with CBZ. She came to the physicians of the Clinical Pharmacokinetic Service (Laboratory of Toxicology of IAHULA, Mérida-Venezuela) requesting a drug monitoring. The results showed a level of 8.51 microg x. mL(-1), which was found within the therapeutic range (4-12 microg x mL(-1)). Subsequently, the dermatologist diagnosed fixed pigmented erythema related to the ingestion of a specific medication which began disappearing after 15 days of CBZ free-treatment and with the aid of a dermatologic formulation.

  4. 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

    2016-04-01

    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.

  5. Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

    Science.gov (United States)

    Mantle, Peter G.; McHugh, Katharine M.; Fincham, John E.

    2010-01-01

    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. PMID:22069673

  6. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    Science.gov (United States)

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron

    2015-01-01

    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  7. Efficacy of continuous oral administration of lanthanum carbonate over 24 months.

    Science.gov (United States)

    Ishizu, Takashi; Hong, Zhang; Matsunaga, Tsuneaki; Kaneko, Yoko; Taru, Yoshinori

    2013-04-01

    To examine the efficacy of long-term administration of lanthanum carbonate, changes in serum Ca, phosphate, whole parathyroid hormone (wPTH), and ALP were examined in 40 patients who were able to tolerate dosage of lanthanum carbonate over a continuous period of 24 months. Concurrently, concomitant administration of other phosphate binders, cinacalcet, vitamin D, etc., was also examined. After 24 months, serum phosphorus levels (P levels) had decreased to within management target of guidelines, from 6.16 ± 1.44 mg/dL to 5.58 ± 1.15 mg/dL, and this effect was maintained for 2 years. There were no changes in Ca level. wPTH did not change significantly but tended to increase at 12 months. The dose of concomitantly administered calcium carbonate and sevelamer hydrochloride was reduced. The P-lowering function of lanthanum carbonate still held steady at 24 months following the start of dosage. Because of the rising trend seen in wPTH, dose of cinacalcet and/or vitamin D need to be modulated. Reducing the number of concomitantly administered phosphate binder tablets was desirable from the standpoint of patient adherence.

  8. Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

    Institute of Scientific and Technical Information of China (English)

    Claudia PMS de Oliveira; Marcelo G de Oliveira; Fernanda I Simplicio; Vicência MR de Lima; Katia Yuahasi; Fabio P Lopasso; Ven(a)ncio AF Alves; Dulcinéia SP Abdalla; Flair J Carrilho; Francisco RM Laurindo

    2006-01-01

    AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model.METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg/day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg/d).Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution.LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 μg protein/mL) were incubated with CuCl2 (300 μmol/L) in the absence and presence of SNAC (300 μmol/L) for 15 h at 37 ℃. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 μmol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 μmol/L) at 37 ℃ in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 μmol/L) and monitored at 234 nm.RESULTS: Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates

  9. A comparison of the pharmacokinetics of three different preparations of total flavones of Hippophae rhamnoides in beagle dogs after oral administration.

    Science.gov (United States)

    Duan, Jingze; Dang, Yang; Meng, Houjun; Wang, Huizhen; Ma, Ping; Li, Guowen; Wu, Tao; Xie, Yan

    2016-06-01

    Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three different total flavones of Hippophae rhamnoides (TFH) preparations were compared after oral administration to beagle dogs by a UPLC-MS method. The pharmacokinetic results showed that C max of isorhamnetin and quercetin in TFH solid dispersion (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly enhanced than that in TFH preparations (p beagle dogs can be significantly increased in TFH-SD and TFH-SE preparations compared to TFH preparations, which was helpful to explore the new forms for oral administration TFH and explain their in vivo processes.

  10. Fifty-six cases of protrusion of lumbar intervertebral disc treated by penetration and oral administration of Chinese decoction plus traction.

    Science.gov (United States)

    Zhong, Q

    2000-12-01

    Fifty-six cases of the protrusion of the lumbar intervertebral disc in the treatment group were treated by drug-penetration and oral administration of traditional Chinese decoction plus traction, and the other 35 cases in the control group by oral administration of Chinese decoction and traction. The results showed that the cure rate in the treatment group was 83.9%, and that in the control group was 57.1%, with a statistically significant difference between the two groups (P lumbar intervertebral disc.

  11. Effects of systemic or topical administration of sodium selenite on early radiation effects in mouse oral mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Gehrisch, A. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ. of Dresden (Germany); Doerr, W. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ. of Dresden (Germany); Experimental Center, Medical Faculty Carl Gustav Carus, Technical Univ. of Dresden (Germany)

    2007-01-15

    Purpose: to quantify the effect of sodium selenite (selenium) on radiation-induced oral mucositis (mouse) after subcutaneous or topical administration. Material and methods: mucosal ulceration of the lower epithelium of mouse tongue was analyzed. Selenium (5 {mu}g) was applied subcutaneously (s.c.) or locally, 60 min or 30 min prior to irradiation, respectively. In combination with single-dose irradiation, a single selenium application was given. With daily fractionated irradiation (3 Gy/fraction) for 1 week (days 0-4), selenium was administered at all 5 days of irradiation. With ten fractions over 2 weeks, selenium was applied in week 1, week 2, or both. All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. Results: in a single-dose control experiment, the ED{sub 50} (dose after which ulcer induction is expected in 50% of the mice) was 12.9 {+-} 1.6 Gy. Selenium increased the ED{sub 50} to 17.7 {+-} 2.6 Gy (s.c.; p = 0.0003) and 16.3 {+-} 3.0 Gy (local; p = 0.0104). The ED{sub 50} for test irradiation after 5 x 3 Gy was 7.4 {+-} 2.2 Gy. Subcutaneous administration of selenium resulted in an ED{sub 50} of 11.5 {+-} 2.0 Gy (p = 0.0015), local application yielded an ED{sub 50} of 10.0 {+-} 2.1 Gy (p = 0.0284). The ED{sub 50} for test irradiation after 10 x 3 Gy/2 weeks was 8.0 {+-} 1.7 Gy. Subcutaneous or local administration of selenium in week 1 yielded a significant increase in ED{sub 50} to 10.5 {+-} 1.0 Gy (p = 0.0069) and 10.7 {+-} 1.0 Gy (p = 0.0039), respectively. By clear contrast, selenium administration in week 2 had no significant effect. Administration in both weeks resulted in an ED{sub 50} of 9.1 {+-} 2.0 Gy (s.c.; p = 0.2747) and 9.7 {+-} 1.4 Gy (local; p = 0.0541). Conclusion: administration of sodium selenite during clinically relevant fractionated irradiation protocols has a significant effect during the initial treatment phase, i.e., week 1 in the mouse. Therefore, in clinical radiotherapy, the

  12. Muscle tissue kinetics of oxytetracycline following intramuscular and oral administration at two dosages to giant freshwater shrimp (Macrobrachium rosenbergii).

    Science.gov (United States)

    Poapolathep, A; Poapolathep, S; Jermnak, U; Imsilp, K; Wannapat, N; Sugita-Konishi, Y; Kumagai, S

    2008-12-01

    The giant river shrimp (Macrobrachium rosenbergii), a native species of Thailand, is either exported for commercial purposes or supplied to meet the local requirements in Thailand. Limited pharmacokinetic information of the major antibiotic, oxytetracycline (OTC), is available for this freshwater shrimp. The purpose of the present study was to investigate the muscle tissue kinetics of OTC in M. rosenbergii following either intramuscular (i.m.) or oral (p.o.) administration at two dosages of 11 and 22 mg/kg body weight (b.w.). The concentration of OTC in shrimp tissues was measured using high-performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations were below the detection limit (LOD, 0.1 microg/g) after 96 and 120 h, following i.m. and p.o. administration, respectively. Peak muscle concentrations (C(max)) were 3.47 and 1.73 microg/g after i.m. and p.o. administration at a single dose of 11 mg/kg b.w. whereas they were 6.03 and 2.51 microg/g at a single dose of 22 mg/kg b.w., respectively. A noncompartment model was developed to describe the pharmacokinetics of OTC in the giant freshwater shrimp. The terminal half-lives of OTC were 28.68 and 28.09 h after i.m. and p.o. administration at a single dose of 11 mg/kg b.w., but 29.95 and 27.03 h at a single dose of 22 mg/kg b.w., respectively. The relative bioavailability was 82.32 and 64.67% following i.m. and p.o. administration, respectively. Based on the pharmacokinetic data, i.m. and p.o. administration with OTC at a dose of 11 mg/kg b.w. would be appropriate for use in giant freshwater shrimp farming. To avoid the OTC residue in shrimp muscle, it should take at least seven half-lives (8 days) to wash out the drug from the muscle of M. rosenbergii.

  13. A pharmacokinetic comparison of meloxicam and ketoprofen following oral administration to healthy dogs.

    Science.gov (United States)

    Montoya, L; Ambros, L; Kreil, V; Bonafine, R; Albarellos, G; Hallu, R; Soraci, A

    2004-07-01

    Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58 +/- 0.38 at 15 min to 5.72 +/- 2.35 at 1 h. The area under the concentration time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(-)-KTP. The mean (+/- SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76 +/- 0.19 h, Cmax = 2.02 +/- 0.41 microg/ml, t1/2el = 1.65 +/- 0.48 h, AUC = 6.06 +/- 1.16 microg.h/ml, Vd/F = 0.39 +/- 0.07 L/kg, Cl/F = 170 +/- 39 ml/(kg.h). The mean (+/- SD) pharmacokinetic parameters of MLX were Tmax = 8.5 +/- 1.91 h, Cmax = 0.82 +/- 0.29 microg/ml, t1/2lambda(z) = 12.13 +/- 2.15 h, AUCinf = 15.41 +/- 1.24 microg.h/ml, Vd/F = 0.23 +/- 0.03 L/ kg, and Cl/F = 10 +/- 1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.

  14. Spironolactone nanocrystals for oral administration: Different pharmacokinetic performances induced by stabilizers.

    Science.gov (United States)

    Mu, Simeng; Li, Mo; Guo, Mengran; Yang, Wenqian; Wang, Yongjun; Li, Jingru; Fu, Qiang; He, Zhonggui

    2016-11-01

    Nanocrystal (NC) technology is an effective strategy to enhance the oral bioavailability for poorly water-soluble drugs. Stabilizers are essential and important in NC formulations due to its ability to decrease the system energy. Studies have revealed that stabilizers can affect the particle size and stability of the system. However, whether stabilizers can affect the in vivo behaviors of the NCs is unknown. To investigate the effects of stabilizers on the in vitro and in vivo performances of NCs, four types of spironolactone (SPN) NCs with similar diameters but different stabilizers were prepared. All the NCs were spherical in shape with a size of about 370nm. In addition, the NCs were also characterized by differential scanning calorimetry, X-ray diffraction, and Raman spectroscopy, the results obtained showed that the SPN in all the formulations was partially amorphous. In fasted state simulated intestinal fluid, all the SPN-NCs showed similar dissolution profiles. However, the dissolution for SPN-NCs/NaDC was suppressed in 0.1M HCl. Importantly, the AUC(0-48h)total for SPN-NCs/F127, SPN-NCs/F68, SPN-NCs/HPMC-E5, and SPN-NCs/NaDC was 4.96-, 3.91-, 2.88- and 1.72-fold higher than that of the SPN suspension, respectively. These results demonstrated that stabilizers in NCs played an important role for the in vivo pharmacokinetic behaviors. It is highly suggested that the ionic stabilizers are not suitable to stabilize drug nanocrystals alone because it may induce aggregation and agglomeration of drug crystals when transferring through the whole gastrointestinal tract and experiencing the different pH levels.

  15. Improved Safety, Bioavailability and Pharmacokinetics of Zidovudine through Lactoferrin Nanoparticles during Oral Administration in Rats.

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    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.

  16. Pharmacokinetics of diclofenac potassium after oral administration of sachets and tablets

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    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.

  17. [Selective induction of dog esophageal carcinomas by the restricted oral administration of N-ethyl-N-'-nitro-N-nitrosoguanidine with a projecting spout].

    Science.gov (United States)

    Tsukahara, Y; Fujita, M; Ohmichi, M; Ishii, T; Taguchi, T

    1989-08-01

    In order to establish an effective method to induce selectively experimental dog esophageal carcinoma, we compared the restricted oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) with projecting spout with the ad libitum oral administration of it. Five dogs were given a solution of ENNG at a concentration of 50mg/l with restricted oral administration with projecting spout for 52 weeks. In all of them, elevated type of esophageal lesions were endoscopically observed soon after the cessation of the ENNG administration. Histological examination revealed that besides the multiple squamous cell carcinomas of the esophagus, various degrees of dysplasias were seen. Two dogs had metastasizes to the regional lymph nodes and one dog had metastatic lesions in the lung. Gastric carcinomas were also seen in four dogs. Another five dogs were given ad libitum the same concentration of ENNG solution. Gastric carcinomas were induced in four dogs, but esophageal carcinomas were seen in small lesions in two dogs. The restricted oral administration of ENNG with projecting spout is a reliable method for the selective induction of esophageal carcinoma in dog.

  18. Effects of oral administration of tripeptides derived from type I collagen (collagen tripeptide) on atherosclerosis development in hypercholesterolemic rabbits.

    Science.gov (United States)

    Tang, Lihua; Sakai, Yasuo; Ueda, Yoshimichi; Katsuda, Shogo

    2015-05-01

    Digestion of type I collagen with a collagenase-type protease yields a collagen tripeptide (Ctp) fraction comprising Gly-X-Y sequences that exhibit diverse biological activities. We previously demonstrated that Ctp inhibits the proliferation and migration of cultured aortic smooth muscle cells (SMCs) in vitro. These cells contribute to the pathogenesis of atherosclerosis and other cardiovascular diseases. In order to evaluate the effects of Ctp on atherosclerosis development in vivo, here we used the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit model of familial hypercholesterolemia to determine the effects of oral administration of Ctp for three months. Ctp induced a significant decrease in the area occupied by atherosclerotic plaques in the aorta and in the level of total serum cholesterol. The components of atherosclerotic plaques underwent distinct changes, including reduction in the populations of macrophages and SMCs and a significant decrease in the proportion of macrophages to SMCs. Ctp administration decreased the number of cells in plaques that expressed proliferating cell nuclear antigen and the number of cells with oxidative damage to DNA as indicated by 8-hydroxy-2'-deoxyguanine detection. These findings are the first to define the mechanism underlying the inhibitory effects of Ctp on atherosclerosis development in hypercholesterolemic rabbits, and suggest that Ctp provides an effective therapy for treating atherosclerosis.

  19. EXPRESSION OF BAX AND BCL-2 IN MOUSE OFFSPRING BRAIN AFIER MATERNAL ORAL ADMINISTRATION OF MONOSODIUM GLUTAMATE

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To analyze the excitotoxicity of monosodium glutamate(MSG)in the offspring crebral cortex and hippocampal subresions after maternal oral administration of MSG.Methods:Kunming mice were given per os MSG(4.0g/kg)at 17-21 days of pregnancy and their offspring behaviors were studied at 10,20,30days postnatally.By using inmunohistochemical means,the involvment of Bcl-2 and bax in the glutamate-induced cell death in cortical and hippocampal neurons were examined.Cell damage was assessed by direct cell counting.Results:administration of monosodium glutamate during the fetal period in mice resulted in a moderate increase in the expression of Bax in principal neurons in CA1,CA2,CA3,CA4 and in the cerebral cortex at postpartum 10,20,30 days in the offspring mice,whereas Bcl-2 protein expressions were reduced significantly in the same regions as compared with those of controls.Conclusion:These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism in which the Bcl-2/Bax-alpha molecular complex may be involved.The glutamate-induced apoptosis appears to be related to the modulation of Bcl-2 family gene products such as Bcl-2 and Bax.

  20. 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

    Introducción: El kéfir es obtenido por fermentación de la leche con una población microbiana compleja presente en sus granos. Al consumo de kéfir se le atribuyen múltiples efectos beneficiosos sobre la salud. Objetivo: Evaluar la toxicidad subcrónica del kéfir en ratas Wistar, administrado por vía oral en dosis normal (normodosis) y sobredosis. Se evaluaron además, los parámetros de peso corporal, hematología, química sanguínea, translocación bacteriana e integridad de la mucosa intestinal. Métodos: Se conformaron tres grupos de seis animales de manera aleatoria: grupo control, recibió 0,7 mL de agua; grupo kéfir recibió 0,7 mL/día de kéfir (normodosis) y grupo Hkéfir recibió 3,5 mL/día de kéfir (dosis cinco veces superior). La administración se llevó a cabo mediante sonda. Los animales se alojaron individualmente, y se mantuvieron bajo las mismas condiciones de manejo y alimentación durante 4 semanas. Resultados: La administración de kéfir en dosis normal y sobredosis no afectó los parámetros evaluados en los animales, el peso corporal, indicadores hematológicos, de química sanguínea, y la patogenicidad potencial en los tejidos se encontraron dentro de límites normales, lo que demostró que el consumo de kéfir en dosis normal y sobredosis es seguro. Además, se evidenció que la administración de normodosis de kéfir redujo los niveles de colesterol y mejoró la mucosa intestinal de las ratas. Conclusión: Se demostró que el consumo de kéfir es seguro. Destacar que, la administración de sobredosis no evidenció daños, no obstante, se recomienda el consumo de normodosis, debido a los marcados efectos beneficiosos y de seguridad.

  1. Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens.

    Science.gov (United States)

    Ji, L-W; Dong, L-L; Ji, H; Feng, X-W; Li, D; Ding, R-L; Jiang, S-X

    2014-06-01

    The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one-compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two-compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the Cmax (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration.

  2. 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 (HgCl2 ). 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 HgCl2 (5 mg kg(-1) body weight) alone or in combination, we found that CO treatment did not protect against HgCl2 -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 HgCl2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl2 (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 HgCl2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl2 -induced oxidative damage.

  3. Comparative pharmacokinetic study of mangiferin after oral administration of pure mangiferin and US patented polyherbal formulation to rats.

    Science.gov (United States)

    Kammalla, Ananth Kumar; Ramasamy, Mohan Kumar; Inampudi, Jyothi; Dubey, Govind Prasad; Agrawal, Aruna; Kaliappan, Ilango

    2015-04-01

    The US patented polyherbal formulation for the prevention and management of type II diabetes and its vascular complications was used for the present study. The xanthone glycoside mangiferin is one of the major effector constituents in the Salacia species with potential anti-diabetic activity. The pharmacokinetic differences of mangiferin following oral administration of pure mangiferin and polyherbal formulation containing Salacia species were studied with approximately the same dose 30 mg/kg mangiferin and its distribution among the major tissue in Wistar rats. Plasma samples were collected at different time points (15, 30, 60, 120, 180, 240, 360, 480, 600, 1,440, 2,160, and 2880 min) and subsequently analyzed using a validated simple and rapid LC-MS method. Plasma concentration versus time profiles were explored by non-compartmental analysis. Mangiferin plasma exposure was significantly increased when administered from formulation compared to the standard mangiferin. Mangiferin resided significantly longer in the body (last mean residence time (MRTlast)) when given in the form of the formulation (3.65 h). Cmax values of formulation (44.16 μg/mL) administration were elevated when compared to equivalent dose of the pure mangiferin (15.23 μg/mL). Tissue distribution study of mangiferin from polyherbal formulation was also studied. In conclusion, the exposure of mangiferin is enhanced after formulation and administration and could result in superior efficacy of polyherbal formulation when compared to an equivalent dose of mangiferin. The results indicate that the reason which delays the elimination of mangiferin and enhances its bioavailability might the interactions of the some other constituents present in the polyherbal formulation. Distribution study results indicate that mangiferin was extensively bound to the various tissues like the small intestine, heart, kidney, spleen, and liver except brain tissue.

  4. Antibiotic treatment for acute haematogenous osteomyelitis of childhood: moving towards shorter courses and oral administration.

    Science.gov (United States)

    Pääkkönen, M; Peltola, H

    2011-10-01

    Acute haematogenous osteomyelitis (AHOM) of childhood usually affects the long bones of the lower limbs. Although almost any agent may cause AHOM, Staphylococcus aureus is the most common bacterium, followed by Streptococcus pneumoniae and, in some countries, Salmonella spp. and Kingella kingae. Magnetic resonance imaging (MRI) has improved the diagnostic accuracy of traditional radiography and scintigraphy. Except for the pre-treatment diagnostic sample from bone before the institution of antibiotic therapy, no other surgery is usually required. Traditionally, non-neonatal AHOM has been treated with a 1-3-month course of antibiotics, including an intravenous (i.v.) phase for the first weeks, but recent prospective randomised studies challenge this approach. For most uncomplicated cases, a course of 20 days including an i.v. period of 2-4 days suffices, provided large enough doses of a well-absorbed agent (clindamycin or a first-generation cephalosporin, local resistance permitting) are used, administration is four times daily and most symptoms and signs subside within a few days. Serum C-reactive protein (CRP) is a good guide in monitoring the course of illness, and the antimicrobial can usually be discontinued if CRP has decreased to <20 mg/L. Newer and costly agents, such as linezolid, should be reserved for cases due to resistant S. aureus strains. AHOM in neonates and immunocompromised patients probably requires a different approach. Because sequelae may develop slowly, follow-up for at least 1 year post hospitalisation is recommended.

  5. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  6. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats

    Directory of Open Access Journals (Sweden)

    Damiana Diniz Rosa

    2014-06-01

    Full Text Available Introduction: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

  7. Serum Calcium Response Following Oral Zinc Oxide Administrations in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Jørgensen RJ

    2001-06-01

    Full Text Available 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 lactating cows dropped dramatically indicating the existence of an antagonistic effect between Zn and Ca. The first Zn induced hypocalcaemic episode in the lactating cows was followed by a rise in serum calcium to a level above the pre-dosing level and above the mean value of the control group. The depth 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 to resistance towards parturient hypocalcaemia.

  8. Intestinal, portal, and peripheral profiles of daikenchuto (TU-100)'s active ingredients after oral administration.

    Science.gov (United States)

    Watanabe, Junko; Kaifuchi, Noriko; Kushida, Hirotaka; Matsumoto, Takashi; Fukutake, Miwako; Nishiyama, Mitsue; Yamamoto, Masahiro; Kono, Toru

    2015-10-01

    A pharmaceutical grade Japanese traditional medicine, daikenchuto (TU-100), consisting of Japanese pepper, processed ginger, and ginseng, has been widely used for various intestinal disorders in Japan and now under development as a new therapeutic drug in the US. It is suggested that TU-100 ingredients exert pharmacological effects on intestines via two routes, from the luminal side before absorption and the peripheral blood stream after absorption. Therefore, in order to fully understand the pharmacological actions of TU-100, it is critically important to know the intraluminal amounts and forms of ingested TU-100 ingredients. In the present study, after administrating TU-100 to rats, the concentrations of TU-100 ingredients and their conjugates in the peripheral and portal blood and ileal contents were determined by LC-MS/MS. Next, TU-100 was administered to patients with ileostomy bags, but whose small intestines are diagnosed as healthy, and the ingredients/conjugates in the ileal effluent were analyzed. The results suggest that: (1) Pepper ingredients hydroxysanshools are rapidly absorbed and enter systemic circulation, (2) Ginseng ingredients ginsenosides are transported to the colon with the least absorption, (3) Ginger ingredients gingerols are absorbed and some conjugated in the small intestine and transported via the portal vein. While only a small amount of gingerols/gingerol conjugates enter systemic circulation, considerable amounts reappear in the small intestine. Thus, the effect of TU-100 on the intestines is believed to be a composite of multiple actions by multiple compounds supplied via multiple routes.

  9. Oral administration with attenuated Salmonella encoding a Trichinella cystatin-like protein elicited host immunity.

    Science.gov (United States)

    Liu, X D; Wang, X L; Bai, X; Liu, X L; Wu, X P; Zhao, Y; Sun, S M; Yu, L; Su, X Z; Wang, Z Q; Wang, F; Liu, M Y

    2014-06-01

    Trichinellosis is a public health problem and is regarded as an emergent/re-emergent disease in various countries. The cDNA encoding a cystatin-like protein (Ts-cystatin) was identified by immunoscreening intestinal muscle larvae cDNA libraries with serum from pigs experimentally infected with 20,000 Trichinella spiralis muscle larvae. To study its impact on host immunity, we chose a eukaryotic expression system based on several comparisons of immunogenicity between the two Salmonella typhimurium administration schemes, which indicated that the eukaryotic expression system was superior. Humoral IgG and mucosal IgA were measured to determine the antibody response. To explore whether Th1 and Th2 responses were responsible for the induced protection, Th1- and Th2-specific cellular transcription factors and the cytokine profile were examined. Changes in the T lymphocyte and macrophage populations were detected by flow cytometry. Lastly, parasitological examination was examined. The results showed that Ts-cystatin induced a Th1/Th2-mixed type of immune response and decreased STAT6 transcription. The intestinal adult recovery increased by 10.9% in the Ts-cystatin group, the Ts-cystatin group fecundity rate was decreased by 91%. Furthermore, the number of muscle larvae did not change compared with the control group. In conclusion, our results suggest that Ts-cystatin plays an important role in Trichinella resistance to rapid expulsion by the host and is worth further study.

  10. Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits.

    Science.gov (United States)

    Leonardi, Irina; Nicholls, Flora; Atrott, Kirstin; Cee, Alexandra; Tewes, Bernhard; Greinwald, Roland; Rogler, Gerhard; Frey-Wagner, Isabelle

    2015-06-01

    Trichuris suis ova (TSO) have shown promising results in the treatment of inflammatory bowel disease (IBD) but the mechanisms which underlies this therapeutic effect cannot be studied in mice and rats as T. suis fails to colonize the rodent intestine, whilst hatching in humans and rabbits. As a suitable rabbit IBD model is currently not available, we developed a rabbit colitis model by administration of dextran sodium sulphate (DSS). White Himalayan rabbits (n = 12) received 0.1% DSS in the daily water supply for five days. Clinical symptoms were monitored daily, and rabbits were sacrificed at different time points. A genomewide expression analysis was performed with RNA isolated from caecal lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC). The disease activity index of DSS rabbits increased up to 2.1 ± 0.4 (n = 6) at day 10 (controls colitis. Localization of the inflammation in the caecum and its similarities to IBD make this model particularly suitable to study TSO therapy in vivo.

  11. Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

    Science.gov (United States)

    Guan, Su; Hu, Chun-Yun; He, Meng-Ying; Yang, Ying-Ying; Tang, Yu-Xin; Chen, Jie-di; Huang, Li-Jie; Tan, Wen

    2015-12-01

    This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

  12. Treatment of Prolapse of Lumbar Intervertebral Disc by Tuina Massotherapy Combined with Oral Administration of Buyang Huanwu Tang——A Report of 75 Cases

    Institute of Scientific and Technical Information of China (English)

    Du Deli; Wang Xinzhong

    2007-01-01

    @@ Prolapse of lumbar intervertebral disc is a commonly encountered disease. From Feb. 2003 - Feb. 2005, a series of 75 cases had been treated by Tuina massotherapy combined with oral administration of Buyang Huanwu Tang (补阳还五汤 Decoction for Invigorating Yang and Recuperation), with satisfactory therapeutic results reported as follows.

  13. Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis

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    Mahy Nicole

    2011-11-01

    Full Text Available Abstract Background Multiple Sclerosis (MS is an acquired inflammatory demyelinating disorder of the central nervous system (CNS and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others neurotoxic agents. Previous studies have demonstrated that microglia expresses ATP-sensitive potassium (KATP channels and its pharmacological activation can provide neuroprotective and anti-inflammatory effects. In this study, we have examined the effect of oral administration of KATP channel opener diazoxide on induced experimental autoimmune encephalomyelitis (EAE, a mouse model of MS. Methods Anti-inflammatory effects of diazoxide were studied on lipopolysaccharide (LPS and interferon gamma (IFNγ-activated microglial cells. EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were orally treated daily with diazoxide or vehicle for 15 days from the day of EAE symptom onset. Treatment starting at the same time as immunization was also assayed. Clinical signs of EAE were monitored and histological studies were performed to analyze tissue damage, demyelination, glial reactivity, axonal loss, neuronal preservation and lymphocyte infiltration. Results Diazoxide inhibited in vitro nitric oxide (NO, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6 production and inducible nitric oxide synthase (iNOS expression by activated microglia without affecting cyclooxygenase-2 (COX-2 expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated EAE clinical signs but did not prevent disease. Histological analysis demonstrated that diazoxide elicited a significant reduction in myelin and axonal loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide did not affect the number of infiltrating lymphocytes positive for CD3 and CD20

  14. Antifertility Effects of Orally Administration of Low Dose Gossypol Acetic Acid Combined with Methyltestosterone Plus Ethinyl Estradiol on Male Rat

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To investigate the feasibility and optimal regimen of orally administration of low close gossypol acetic acid (GA) combined with methyltestosterone (MT) plus ethinyl estradiol (EE) for contraception in males.Methods Wistar male rats were randomly assigned into four groups, 20 in each group. Animals in group A or B were administered daily with 1% methyl cellulose or GA (12 mg/kg) suspended in 1% methyl cellulose, respectively. Rats in group C or D took firstly GA 12 mg/kg+MT 20 mg/kg+EE 0.1 mg/kg or MT 20 mg/kg+EE 0.1 mg/kg, in a suspension with 1% methyl cellulose, via gastric intubation. After the infertilities were initiated(6 weeks for group C, 8 weeks for group D), GA was served alone while MT+EE were withdrawn in rats of groups C and D. The treatment was ceased after 18 weeks and some males from group C were permitted to recover. Fertility testing, 10 males per group, was served for determining infertility or restoration of fertility in treated rats. Examinations of histology and biochemistry in treated rats were used to examine the morphologic influences on sperm, testis, epididymides and viscera, and biochemical changes in blood. The growth and development of F1 generation of the rats would also be tested in a series of behavioral tests.Results Ten rats from group C were infertile at week 6 after treatment, and the fulfilled infertility was maintained with low-close GA (12 mg/kg) only daily. Six weeks after cessation of treatment, all of treated males recovered their fertility. However, 8 of 10 rats from group D were in sterility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the similar dose GA alone later on. Moreover, no adverse effects were found in our present experiments.Conclusion Administration of oral low dose GA combined with MT and EE as loading dose could successfully induce infertility in short term, whereafter the efficacy could completely be maintained by similar low dose of GA

  15. Pharmacokinetics and tissue distribution of thiamphenicol and florfenicol in Pacific white shrimp Litopenaeus vannamei in freshwater following oral administration.

    Science.gov (United States)

    Fang, Wenhong; Li, Guolie; Zhou, Shuai; Li, Xincang; Hu, Linlin; Zhou, Junfang

    2013-06-01

    This study evaluated the pharmacokinetic disposition of thiamphenicol (THA) and florfenicol (FLR) after oral administration of each at a single dose of 10 mg/kg body weight in Pacific white shrimp Litopenaeus vannamei held in freshwater at 25.0 ± 1.0°C. The THA and FLR concentrations in the hemolymph, muscle, and hepatopancreas were determined by HPLC. The profiles of hemolymph THA and FLR concentrations versus time were best described by a two-compartment open pharmacokinetic model with first-order absorption. The peak concentration (C max), peak time (T max), absorption half-life (t 1/2ka) and elimination half-life (t 1/2β) of THA in hemolymph were 7.96 μg/mL, 2 h, 0.666 h, and 10.659 h, respectively. The corresponding values for FLR were 5.53 μg/mL, 2 h, 1.069 h, and 17.360 h, respectively. After oral administration, THA and FLR were rapidly absorbed in white shrimp and THA in hemolymph was absorbed and eliminated more quickly than FLR. The parameters in muscle and hepatopancreas were calculated by a noncompartment model based on statistical moment theory. The C max, area under the concentration-time curve (AUC0-t ), mean residue time (MRT0-t ), and half-life (t 1/2z) in muscle were 2.98 μg/g, 29.10 mg/kg·h, 9.77 h, and 6.84 h, respectively. The corresponding values for FLR were 1.91 μg/g, 15.97 mg/kg·h, 19.40 h, and 18.32 h, respectively. In muscle THA was eliminated more quickly than FLR. The peak concentrations of THA and FLR in the hepatopancreas were 204.25 and 164.22 μg/g, respectively, and the values for AUC0-t were 1,337.74 and 871.73 mg/kg·h, respectively, which were much higher than those in hemolymph and muscle. The in vitro protein-binding value of THA (28.38%) was lower than that of FLR (37.91%), which might be related to the finding that THA in Pacific white shrimp was absorbed and eliminated more quickly than FLR. Received July 21, 2012; accepted November 23, 2012.

  16. 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

  17. Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations

    Institute of Scientific and Technical Information of China (English)

    Hong-yun WANG; Pei HU; Ji JIANG

    2011-01-01

    To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers.Methods:This was an open-label,single- and multiple-dose study.The subjects were assigned to receive a single dose,675,2025,or 4050 mg,of calcium L-threonate (n=12) or repeated doses of 2025 mg twice daily for 4 d (n=12).Serial plasma and urine samples were analyzed with HPLC-MS/MS.Pharmacokinetic parameters of L-threonate were calculated using non-compartmental analysis with WinNonlin software.Results:In the single dose group,Cmax reached at 2.0 h and the mean t1/2 was approximately 2.5 h.Area under.curve (AUC) and Cmax increased with dose escalation,but dose proportionality was not observed over the range of 675 to 4050 mg.AUC and Cmax in the fasted subjects were lower compared with those in the non-fasted subjects.Cumulative urinary excretion of L-threonate over 24 h represented 5.9% of the administered dose with a mean CI/r of 0.8 L/h.In the multiple-dose study,no accumulation appeared upon repeated doses of 2025 mg twice daily for 4 d.There were no serious adverse events that occurred during this study.Conclusion:Calcium L-threonate was well tolerated in healthy Chinese subjects,with no pattern of dose-related adverse events.Plasma exposure increased with dose escalation,but linear pharmacokinetics were not observed over the studied doses.L-threonate was absorbed rapidly,and its absorption was enhanced by food intake.No systemic accumulation appeared after repeated administrations.

  18. 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.

  19. Pharmacokinetics, Tissue Distribution and Excretion of Isoalantolactone and Alantolactone in Rats after Oral Administration of Radix Inulae Extract

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    Renjie Xu

    2015-04-01

    Full Text Available Radix Inulae is endemic to China and has been used in traditional medicine to treat upper body pain, emesis and diarrhoea, and to eliminate parasites. Here, an UPLC-MS/MS method was developed and applied to study the pharmacokinetics, distribution and excretion of isoalantolactone and alantolactone, which are two main active sesquiterpene lactones in Radix Inulae, in Sprague-Dawley rats following oral administration of total Radix Inulae extract. Isoalantolactone, alantolactone and osthole (internal standard were prepared using acetonitrile precipitation, and the separation of isoalantolactone and alantolactone was achieved by isocratic elution using water (containing 0.1% formic acid and acetonitrile as the mobile phase using a ZORBAX Eclipse Plus C18 column. The total run time was 6.4 min. The present study showed poor absorption of isoalantolactone and alantolactone in vivo. The apparent Cmax, Tmax, T1/2 and total exposure (AUC0–12h in rat plasma were 37.8 ng/mL, 120 min, 351.7 min and 6112.3 ng-min/mL for isoalantolactone and 25.9 ng/mL, 90 min, 321.0 min and 4918.9 ng-min/mL for alantolactone, respectively. It was shown that the highest concentration was achieved in the small intestine and feces clearance was shown to be the dominant elimination pathway of the lactones.

  20. Pharmacokinetics, tissue distribution and excretion of isoalantolactone and alantolactone in rats after oral administration of Radix Inulae extract.

    Science.gov (United States)

    Xu, Renjie; Zhou, Guisheng; Peng, Ying; Wang, Mengyue; Li, Xiaobo

    2015-04-28

    Radix Inulae is endemic to China and has been used in traditional medicine to treat upper body pain, emesis and diarrhoea, and to eliminate parasites. Here, an UPLC-MS/MS method was developed and applied to study the pharmacokinetics, distribution and excretion of isoalantolactone and alantolactone, which are two main active sesquiterpene lactones in Radix Inulae, in Sprague-Dawley rats following oral administration of total Radix Inulae extract. Isoalantolactone, alantolactone and osthole (internal standard) were prepared using acetonitrile precipitation, and the separation of isoalantolactone and alantolactone was achieved by isocratic elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase using a ZORBAX Eclipse Plus C18 column. The total run time was 6.4 min. The present study showed poor absorption of isoalantolactone and alantolactone in vivo. The apparent Cmax, Tmax, T1/2 and total exposure (AUC0-12h) in rat plasma were 37.8 ng/mL, 120 min, 351.7 min and 6112.3 ng-min/mL for isoalantolactone and 25.9 ng/mL, 90 min, 321.0 min and 4918.9 ng-min/mL for alantolactone, respectively. It was shown that the highest concentration was achieved in the small intestine and feces clearance was shown to be the dominant elimination pathway of the lactones.

  1. Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration

    Directory of Open Access Journals (Sweden)

    Emilio Jirillo

    1993-01-01

    Full Text Available Tuberculosis (TBC is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC. This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-α, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis.

  2. LC-ESI-MS/MS analysis of quercetin in rat plasma after oral administration of biodegradable nanoparticles.

    Science.gov (United States)

    V, Dinesh Kumar; Verma, Priya Ranjan Prasad; Singh, Sandeep Kumar; Viswanathan, S

    2015-11-01

    A simple, rapid and sensitive LC-MS/MS method was developed and validated for the determination of free quercetin in rat plasma, using fisetin as internal standard. The detection was performed by negative ion electrospray ionization under selected reaction monitoring. Chromatographic separation (isocratic elution) was carried out using acetonitrile-10 m m ammonium formate (80:20, v/v) with 0.1% v/v formic acid. The lower limit of quantification (4.928 ng/mL) provided high sensitivity for the detection of quercetin in rat plasma. The linearity range was from 5 to 2000 ng/mL. Intra- and inter-day variability (RSD) of quercetin extraction from rat plasma was quercetin in rat plasma, after oral administration of quercetin-loaded biodegradable nanoparticles (QLN) and quercetin suspension. QLN (C(max), 1277.34 ± 216.67 ng/mL; AUC, 17,458.25 ± 3152.95 ng hr/mL) showed a 5.38-fold increase in relative bioavailability as compared with quercetin suspension (C(max), 369.2 ± 108.07 ng/mL; AUC, 3276.92 ± 396.67 ng hr/mL).

  3. Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

    Science.gov (United States)

    de Boer, Johannes D; Berkhout, Lea C; de Stoppelaar, Sacha F; Yang, Jack; Ottenhoff, Roelof; Meijers, Joost C M; Roelofs, Joris J T H; van't Veer, Cornelis; van der Poll, Tom

    2015-10-15

    Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

  4. Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Zipeng Gong

    2014-01-01

    Full Text Available A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight was performed in normal and postinflammation irritable bowel syndrome (PI-IBS rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as Cmax⁡, AUC(0–t, Vd/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status.

  5. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice

    Indian Academy of Sciences (India)

    Jingtao Hu; Chunfeng Wang; Liping Ye; Wentao Yang; Haibin Huang; Fei Meng; Shaohua Shi; Zhuang Ding

    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- (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.

  6. 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 meloxicam both alone and in combination with levofloxacin, whereas an increase (p meloxicam-alone treated group and inhibited (p meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p meloxicam both alone and in combination with levofloxacin (p meloxicam.

  7. Serum Pharmacochemistry Analysis Using UPLC-Q-TOF/MS after Oral Administration to Rats of Shenfu Decoction

    Directory of Open Access Journals (Sweden)

    Jia-le He

    2015-01-01

    Full Text Available The purpose of this study was to study the serum pharmacochemistry of SFD as well as the material basis through analyzing the constituents absorbed in blood. The SFD was orally administrated to Wistar rats at 20 g·kg−1, and Ultra Performance Liquid Chromatography (UPLC fingerprints of SFD were created. Serum samples were collected for analysis, and further data processing used MarkerLynx XS software. 19 ginsenosides and 16 alkaloids were detected in SFD. The absorption of alkaloids (mainly monoester diterpenoid alkaloids increased when Aconitum carmichaeli Debx. was combined with Panax ginseng, while the ginsenosides remained stable. Diester diterpenoid alkaloids were not present in the serum samples. A suitable serum pharmacochemistry method was successfully established to study pharmacological effects and potential improvements in formulation. This may also be useful for toxicity reduction. We suspect that the increased absorption of the monoester diterpenoid alkaloids from the mixture of Panax and Radix, compared to the Panax only extract, may be the reason for the combination of the two herbs in popular medicine formulas in China.

  8. 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.

  9. Whole-body tissue distribution of total radioactivity in rats after oral administration of [¹⁴C]-bilastine.

    Science.gov (United States)

    Lucero, María Luisa; Patterson, Andrew B

    2012-06-01

    This study evaluated the tissue distribution of total radioactivity in male albino, male pigmented, and time-mated female albino rats after oral administration of a single dose of [¹⁴C]-bilastine (20 mg/kg). Although only 1 animal was analyzed at each time point, there were apparent differences in bilastine distribution. Radioactivity was distributed to only a few tissues at low levels in male rats, whereas distribution was more extensive and at higher levels in female rats. This may be a simple sex-related difference. In each group and at each time point, concentrations of radioactivity were high in the liver and kidney, reflecting the role of these organs in the elimination process. In male albino rats, no radioactivity was measurable by 72 hours postdose. In male pigmented rats, only the eye and uveal tract had measurable levels of radioactivity at 24 hours. Measureable levels of radioactivity were retained in these tissues at the final sampling time point (336 hours postdose), indicating a degree of melanin-associated binding. In time-mated female rats, but not in albino or pigmented male rats, there was evidence of low-level passage of radioactivity across the placental barrier into fetal tissues as well as low-level transfer of radioactivity into the brain.

  10. Metabolism and pharmacokinetics of barnidipine hydrochloride, a calcium channel blocker, in man following oral administration of its sustained release formulation.

    Science.gov (United States)

    Teramura, T; Watanabe, T; Higuchi, S; Hashimoto, K

    1997-02-01

    1. The metabolism and pharmacokinetics of barnidipine hydrochloride, a 1, 4-dihydropyridine calcium antagonist were evaluated following single oral administration of a sustained release formulation (SR) capsule comprising of quick and slow release pellets to healthy male volunteers. 2. Various metabolites were identified and quantitated by newly established GC-MS analytical methods. Major metabolites were the hydrolyzed product of the benzyl-pyrrolidinyl ester (M-3) in plasma and its oxidized pyridine product (M-4) in plasma and urine. The pyridine form of unchanged barnidipine and the N-debenzylated product were observed as minor metabolites. Therefore, the primary metabolic pathways in man are (a) hydrolysis of the benzylpyrrolidine ester, (b) N-debenzylation, and (c) oxidation of the dihydropyridine ring. 3. When the SR and normal capsules were administered at a dose of 10 mg to six subjects in a crossover design, AUC 0-infinity of unchanged drug, M-3 and 4 in each subject receiving the SR were 97 +/- 15, 85 +/- 31 and 76 +/- 21% respectively of those subjects receiving the normal formulation. The sum of the excretion of urinary metabolites for the SR formulation was 65 +/- 6% of that for the normal formulation. These data suggest that the absorption of the SR formulation is slightly reduced but that its bioavailability is comparable to that of the normal formulation.

  11. Oral administration of an enzymatic protein hydrolysate from the green microalga Chlorella vulgaris enhances the nutritional recovery of malnourished mice.

    Science.gov (United States)

    Morris, Humberto J; Carrillo, Olimpia V; Alonso, María E; Bermúdez, Rosa C; Almarales, Ángel; Llauradó, Gabriel; Lebeque, Yamila; Fontaine, Roberto

    2011-12-01

    This study examined the effects of oral administration of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris (Cv-PH) on the nutritional recovery of malnourished Balb/c mice after a 3-day fasting period. Mice were refed with commercial diet supplemented or not supplemented with Cv-PH (500 mg/kg) for 8 days. Regardless of the diet used during refeeding, animal body weights and serum protein concentrations did not differ between groups. Mice given Cv-PH had a significant increase in hemoglobin concentrations. Most serum amino acid levels were similar in the control and Cv-PH animals. Starved mice refed with Cv-PH showed normal liver functions, as judged by liver weight, protein concentration, and the enzymatic activities of cholinesterase and arginase. Cv-PH increased DNA, protein content, and gut-mucosal weight. In addition, brush-border oligosaccharidase activities were also higher in the Cv-PH group. These findings suggest that Chlorella protein hydrolysate can be used to develop specific formulations suitable for pharmacologic nutrition.

  12. Protection against Flavobacterium psychrophilum infection (cold water disease) in Ayu fish (Plecoglossus altivelis) by oral administration of humus extract.

    Science.gov (United States)

    NAKAGAWA, Jun; IWASAKI, Tadashi; KODAMA, Hiroshi

    2009-11-01

    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms have been present. In the present study, oral administration of humus extract to ayu fish (Plecoglossus altivelis) induced effective protection against experimental Flavobacterium psychrophilum infection (cold water disease). Mortality of fish and development of skin lesions, such as erosion and hemorrhages on the skin, gill cover or mouth, were significantly suppressed in fish treated with 10%, 5% or 1% humus extract adsorbed on dry pellets. Although F. psychrophilum was not re-isolated from gills and erosion lesions of the skin of dead fish, bacterial gyrB DNA could be amplified in these specimens from dead fish and surviving control fish using the polymerase chain reaction. The protective effect of the extract was not the results of direct killing of bacteria or antibiotic activity of the extract since no obvious reduction in the bacterial number was observed at 5 times to 5,000 times dilution of the humus extract having pH 5.45 to 7.40. These results clearly show that treating fish with humus extract is effective in preventing cold water disease.

  13. Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus.

    Science.gov (United States)

    Sun, Wei; He, Yi-Sheng; Xu, Ling-Hui; Zhang, Bi-Ying; Qi, Lian-Wen; Yang, Jie; Li, Ping; Wen, Xiao-Dong

    2016-09-01

    Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm × 50 mm, 1.8 μm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL·min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.

  14. In vivo study of the mucus-permeating properties of PEG-coated nanoparticles following oral administration.

    Science.gov (United States)

    Inchaurraga, Laura; Martín-Arbella, Nekane; Zabaleta, Virginia; Quincoces, Gemma; Peñuelas, Ivan; Irache, Juan M

    2015-11-01

    The aim of this work was to investigate the mucus-permeating properties of poly(ethyleneglycol)-coated nanoparticles prepared from the copolymer of methyl vinyl ether and maleic anhydride (Gantrez® AN) after oral administration in rats. Nanoparticles were "decorated" with PEGs of different molecular masses (PEG2000, PEG6000 and PEG10000) at a PEG-to-polymer ratio of 0.125. All the PEG-coated nanoparticles displayed a mean size of ∼150 nm, slightly negative ζ values and a "brush" conformation as determined from the calculation of the PEG density. For in vivo studies, nanoparticles were labelled with either (99m)Tc or fluorescent tags. Naked nanoparticles displayed a higher ability to interact with the mucosa of the stomach than with the small intestine. However, these interactions were restricted to the mucus layer covering the epithelial surface, as visualised by fluorescence microscopy. On the contrary, PEG-coated nanoparticles moved rapidly to the intestine, as determined by imaging, and, then, were capable to develop important interactions with the mucosa, reaching the surface of the epithelium. These mucus permeating properties were more intense for nanoparticles coated with PEG2000 or PEG6000 than with PEG10000. However, the capability of nanocarriers to develop adhesive interactions within the mucosa decreased when prepared at excessive PEG densities.

  15. Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [(13) C8 ]-evacetrapib as a tracer.

    Science.gov (United States)

    Cannady, Ellen A; Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G; Royalty, Jane; Ortega, Demetrio; Pack, Brian W; Begum, Syeda L; Annes, William F; Lin, Qun; Small, David S

    2016-05-30

    This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration-time curve (AUC) from zero to infinity (AUC[0-∞]) and to the last measureable concentration (AUC[0-tlast ]), were calculated. Bioavailability was calculated as the ratio of least-squares geometric mean of dose-normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2-47.6%) for AUC(0-∞) and 44.3% (90% CI: 41.8-46.9%) for AUC(0-tlast ). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a (13) C-labeled IV microdose tracer at about 1/1000(th) the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability.

  16. Comparative disposition of 2,3-epoxy-1-propanol (glycidol) in rats following oral and intravenous administration.

    Science.gov (United States)

    Nomeir, A A; Silveira, D M; Ferrala, N F; Markham, P M; McComish, M F; Ghanayem, B I; Chadwick, M

    1995-02-01

    Glycidol (2,3-epoxy-1-propanol), an industrial chemical, has been shown to be a reproductive toxicant in short-term studies and a carcinogen in rats and mice in oncogenicity studies. The reproductive toxicity of glycidol was believed to result from its conversion to alpha-chlorohydrin by the action of HCl in the stomach. The comparative disposition of glycidol was investigated in rats following oral (po) or intravenous (iv) administration at doses of 37.5 and 75 mg/kg. These were the doses used in the National Toxicology Program (NTP) oncogenicity study with glycidol. Approximately 87-92% of the dose was absorbed from the gastrointestinal tract of the rat. [14C]Glycidol equivalents were eliminated in urine (40-48% of dose in 72 h), feces (5-12%), and exhaled as CO2 (26-32%). At both doses, 9-12% and 7-8% (estimated) of the dose remained in tissues at 24 and 72 h following dosing, respectively. In general, the concentrations of glycidol equivalents in tissues were proportional to the dose. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney, and spleen, and the lowest in adipose tissue, skeletal muscle, and plasma. The pattern of distribution of radioactivity in tissues was similar for both the iv and po routes. The total recovery of radioactivity ranged from 87 to 91% of dose. Urinary radioactivity was resolved by high-performance liquid chromatography (HPLC) analysis into 15 metabolites. There were one major (14-21% of the dose) and four lesser metabolites (each representing 2-8%); the others were minor, each representing 1% or less of the dose. In general, the urinary metabolic profile was similar following either iv or po administration at the two doses studied. Previous studies by other investigators suggested that alpha-chlorohydrin, which was presumably formed from glycidol by the HCl in the stomach, was metabolized and excreted in urine as beta-chlorolactic acid. The results of the present study show that very

  17. Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen.

    Science.gov (United States)

    Nitta, Kyoko; Shi, Sen; Nagai, Takako; Kanasaki, Megumi; Kitada, Munehiro; Srivastava, Swayam Prakash; Haneda, Masakazu; Kanasaki, Keizo; Koya, Daisuke

    2016-01-01

    Kidney fibrosis is the final common pathway of progressive kidney diseases including diabetic nephropathy. Here, we report that the endogenous antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), the substrate of angiotensin-converting enzyme (ACE), is an orally available peptide drug used to cure kidney fibrosis in diabetic mice. We utilized two mouse models of diabetic nephropathy, streptozotocin- (STZ-) induced type 1 diabetic CD-1 mice and type 2 diabetic nephropathy model db/db mice. Intervention with the ACE inhibitor imidapril, oral AcSDKP, or imidapril + oral AcSDKP combination therapy increased urine AcSDKP levels. AcSDKP levels were significantly higher in the combination group compared to those of the other groups. AcSDKP oral administration, either AcSDKP alone or in addition to imidapril, ameliorated glomerulosclerosis and tubulointerstitial fibrosis. Plasma cystatin C levels were higher in both models, at euthanasia, and were restored by all the treatment groups. The levels of antifibrotic miRs, such as miR-29 or let-7, were suppressed in the kidneys of both models; all treatments, especially the combination of imidapril + oral AcSDKP, restored the antifibrotic miR levels to a normal value or even higher. AcSDKP may be an oral antifibrotic peptide drug that would be relevant to combating fibroproliferative kidney diseases such as diabetic nephropathy.

  18. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    Science.gov (United States)

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  19. Safety evaluation of an oak-flavored milk powder containing ellagitannins upon oral administration in the rat.

    Science.gov (United States)

    Azorín-Ortuño, María; Urbán, Cristina; Cerón, José J; Tecles, Fernando; Gil-Izquierdo, Angel; Pallarés, Francisco J; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2008-04-23

    Ellagitannins are phenolic compounds that occur in a number of dietary sources such as walnuts, raspberries, pomegranate, strawberries, and oak-aged wines. Ellagitannins have been acknowledged to have antioxidant and cancer chemopreventive activities. However, ellagitannins have also been considered to be "antinutrients" and have been reported to provoke adverse effects in animals. In this context, risk assessment studies are demanded to ensure that chemicals present in food do not compromise food safety. Oak-flavored milk can be obtained by thermal treatment of milk in the presence of oak shavings. The oak-flavored milk can be used to impart wood-like flavor to different recipes. The present study evaluated, under a subchronic approach, the safety of an oak-flavored milk powder containing ellagitannins in rats upon repeated oral administration for 96 days. The effect of 30% oak-flavored milk powder in the diet was evaluated. This amount involved a margin of safety equivalent to the daily intake of 134 yogurts by a 70 kg person for 96 days. Growth rate, food utility index, 9 hematological, and 13 serobiochemical parameters as well as the metabolism and tissue distribution of ellagitannins and derived metabolites were studied. Overall, no significant differences were found in oak-milk-fed rats in any blood parameter analyzed. No effect was found on growth rate and food utility index. Urolithin A was identified in feces of rats fed oak-flavored milk and the glucuronide derivative in urine. No metabolites were found in the liver, kidney, or uterus. Histopathological analysis of liver and kidney corroborated the absence of toxicity. Therefore, these results suggest that the intake of the oak-flavored milk powder assayed in this study is safe and does not involve potential hazard to human health.

  20. A 1H-NMR Based Study on Hemolymph Metabolomics in Eri Silkworm after Oral Administration of 1-Deoxynojirimycin.

    Science.gov (United States)

    Deng, Ming-Jie; Lin, Xiao-Dong; Lin, Qiu-Ting; Wen, De-Fu; Zhang, Mei-Ling; Wang, Xian-Qin; Gao, Hong-Chang; Xu, Jia-Ping

    2015-01-01

    We aimed to investigate whether 1-deoxynojirimycin (DNJ) modulates glycometabolism and has toxicity in Eri silkworm (Samia cynthia ricini, Saturniidae). In this paper, hemolymph metabolites were used to explore metabolic changes after oral administration of DNJ or mulberry latex and to characterize the biological function of DNJ at the metabolic and systemic levels. Hemolymph samples were collected from fourth-instar larvae of Eri silkworm and ex-vivo high-resolution 1H nuclear magnetic resonance (NMR) spectra were acquired from the collected hemolymph samples. Then the obtained spectra were analyzed by principal component analysis (PCA) and independent-samples t-test. Metabolic pattern recognition analysis of hemolymph samples indicated that the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1) were significantly different from the control group. Moreover, compared to the control group, the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1) showed the decreased levels of citrate, succinate, fumarate, malate, and glutamine in hemolymph, the groups of 0.25% DNJ and the mixture of 0.5% DNJ and latex (1:1) showed the increased levels of trehalose and lactate. In addition, mulberry leaves exude latex was highly toxic to Eri silkworm because rich unidentified high-molecular-weight factor (s) acted as toxic substances. In our results, latex caused 20 deaths among 50 fourth-instar larvae of Eri silkmoth, but DNJ or the mixture did not caused death. All these results suggest that DNJ has a positive impact on the reverse glycometabolism by modulating glycometabolism and inhibiting glucogenesis and energy metabolism. DNJ is a secure substance as a single-ingredient antidiabetic medicine due to its nontoxicity and bioactivity.

  1. A 1H-NMR Based Study on Hemolymph Metabolomics in Eri Silkworm after Oral Administration of 1-Deoxynojirimycin.

    Directory of Open Access Journals (Sweden)

    Ming-Jie Deng

    Full Text Available We aimed to investigate whether 1-deoxynojirimycin (DNJ modulates glycometabolism and has toxicity in Eri silkworm (Samia cynthia ricini, Saturniidae. In this paper, hemolymph metabolites were used to explore metabolic changes after oral administration of DNJ or mulberry latex and to characterize the biological function of DNJ at the metabolic and systemic levels. Hemolymph samples were collected from fourth-instar larvae of Eri silkworm and ex-vivo high-resolution 1H nuclear magnetic resonance (NMR spectra were acquired from the collected hemolymph samples. Then the obtained spectra were analyzed by principal component analysis (PCA and independent-samples t-test. Metabolic pattern recognition analysis of hemolymph samples indicated that the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1 were significantly different from the control group. Moreover, compared to the control group, the groups of 0.25% DNJ, latex, and the mixture of 0.5% DNJ and latex (1:1 showed the decreased levels of citrate, succinate, fumarate, malate, and glutamine in hemolymph, the groups of 0.25% DNJ and the mixture of 0.5% DNJ and latex (1:1 showed the increased levels of trehalose and lactate. In addition, mulberry leaves exude latex was highly toxic to Eri silkworm because rich unidentified high-molecular-weight factor (s acted as toxic substances. In our results, latex caused 20 deaths among 50 fourth-instar larvae of Eri silkmoth, but DNJ or the mixture did not caused death. All these results suggest that DNJ has a positive impact on the reverse glycometabolism by modulating glycometabolism and inhibiting glucogenesis and energy metabolism. DNJ is a secure substance as a single-ingredient antidiabetic medicine due to its nontoxicity and bioactivity.

  2. Increased mRNA expression of interferon-induced Mx1 and immunomodulation following oral administration of IFN-alpha2b-transformed B. longum to mice.

    Science.gov (United States)

    Yu, Zhijian; Zeng, Zhongming; Huang, Zhen; Lian, Jie; Yang, Jin; Deng, Qiwen; Zeng, Weiseng

    2010-08-01

    We previously constructed an arabinose-inducible recombinant Bifidobacterium longum that could efficiently express secreted IFN-alpha2b in vitro (Deng et al. in Arch Microbiol 191:681-686, 2009). Here, we investigated the influence of oral pBAD-SPIFN-transformed B. longum on immunomodulation and IFN-induced Mx1 gene transcription in mice. We observed enhanced serum and fecal IFN-alpha2b concentrations in mice orally administered recombinant B. longum, suggesting a possible Th1 pattern of induction in the spleen and Peyer's patches. Transcription of the typically IFN-induced antiviral Mx1 gene in the hepatic and intestinal tissues of these mice was also markedly enhanced. In conclusion, oral administration of the recombinant B. longum expressing IFN-alpha2b might play its roles in the immunomodulation of the mice, and the potential clinical value of this bacterium in the treatment of viral infections needs to be further studied.

  3. Expression profile of key immune-related genes in Penaeus monodon juveniles after oral administration of recombinant envelope protein VP28 of white spot syndrome virus.

    Science.gov (United States)

    Thomas, Ancy; Sudheer, Naduvilamuriparampu Saidumuhammed; Kiron, Viswanath; Bright Singh, Issac S; Narayanan, Rangarajan Badri

    2016-07-01

    White spot syndrome virus (WSSV) is the most catastrophic pathogen the shrimp industry has ever encountered. VP28, the abundant envelope protein of WSSV was expressed in bacteria, the purified protein administered orally to Penaeus monodon juveniles and its immune modulatory effects examined. The results indicated significant up-regulation of caspase, penaeidin, crustin, astakine, syntenin, PmRACK, Rab7, STAT and C-type lectin in animals orally administered with this antigen. This revealed the immune modulations in shrimps followed by oral administration of rVP28P which resulted in the reduced transcription of viral gene vp28 and delay in mortality after WSSV challenge. The study suggests the potential of rVP28P to elicit a non-specific immune stimulation in shrimps.

  4. 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

  5. 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 w

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

    NARCIS (Netherlands)

    Dorhout, B; van Faassen, A; van Beusekom, C M; Kingma, A W; de Hoog, E; Nagel, G T; Karrenbeld, A; Boersma, E R; Muskiet, F A

    1997-01-01

    Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuter

  7. Induction of protective immune responses against the challenge of Actinobacillus pleuropneumoniae by the oral administration of transgenic tobacco plant expressing ApxIIA toxin from the bacteria.

    Science.gov (United States)

    Lee, Kyung-Yeol; Kim, Dong-Heon; Kang, Tae-Jin; Kim, Ju; Chung, Gook-Hyun; Yoo, Han-Sang; Arntzen, Charles J; Yang, Moon-Sik; Jang, Yong-Suk

    2006-12-01

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. Among the virulence factors, ApxIIA, a bacterial exotoxin, is reportedly expressed in many serotypes and is considered as a candidate for the development of a vaccine against the bacterial infection. Previously, we isolated a field strain of A. pleuropneumoniae serotype 2 in Korea and characterized its exotoxins to develop an oral vaccine. In this study, we initially confirmed the immunogenicity of ApxIIA expressed in Escherichia coli. We then developed transgenic tobacco expressing ApxIIA and tested its efficacy to induce a protective immune response against A. pleuropneumoniae infection after oral administration of the plant powder. We observed that protective immune responses were induced in mice after oral administration of the plant powder once a week for 4 weeks. Immunoassays revealed that the levels of antigen-specific immunoglobulin G against ApxIIA increased in mice that were fed a powder made from the transgenic plant, but not in mice fed a powder made from wild-type tobacco. Additionally, mice fed the transgenic plant powder were protected from an injection of a lethal dose of A. pleuropneumoniae. These results support that the transgenic plant may be a suitable candidate for an oral vaccine that could be used effectively against A. pleuropneumoniae infection.

  8. A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

    OpenAIRE

    1984-01-01

    The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.00...

  9. Oral Administration and External Application of Chinese Drugs Combined with Micro-invasive Operation for the Treatment of Varicose Ulcers in the Lower Extremities

    Institute of Scientific and Technical Information of China (English)

    王小平; 张宇; 粟文娟; 王珊珊; 王英

    2009-01-01

    Objective:To evaluate the clinical therapeutic effects of oral administration and external application of Chinese drugs combined with micro-invasive surgery for the treatment of varicose ulcers in the lower extremities(ecthyma).Methods:A total of 152 patients(163 limbs) suffering from varicose ulcers on the lower limbs were assigned to two groups according to the patients' willingness.The 102 cases(109 limbs) in the treatment group underwent the method of endovenous microwave closure of communicating vei...

  10. Treatment of Irritable Bowel Syndrome by Oral Administration of Chinese Medicines and Retention-Enema—— A Report of 50 Cases

    Institute of Scientific and Technical Information of China (English)

    段国玉

    2002-01-01

    @@ Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.

  11. Oral Fluid with Three Modes of Collection and Plasma Methamphetamine and Amphetamine Enantiomer Concentrations After Controlled Intranasal l-Methamphetamine Administration

    OpenAIRE

    Newmeyer, Matthew N.; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A.; Huestis, Marilyn A.

    2015-01-01

    Methamphetamine is included in drug testing programs due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks VapoInhaler administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices a...

  12. Induction of immune responses in mice and pigs by oral administration of classical swine fever virus E2 protein expressed in rice calli.

    Science.gov (United States)

    Jung, Myunghwan; Shin, Yun Ji; Kim, Ju; Cha, Seung-Bin; Lee, Won-Jung; Shin, Min-Kyoung; Shin, Seung Won; Yang, Moon-Sik; Jang, Yong-Suk; Kwon, Tae-Ho; Yoo, Han Sang

    2014-12-01

    Classical swine fever (CSF), caused by the CSF virus (CSFV), is a highly contagious disease in pigs. In Korea, vaccination using a live-attenuated strain (LOM strain) has been used to control the disease. However, parenteral vaccination using a live-attenuated strain still faces a number of problems related to storage, cost, injection stress, and differentiation of CSFV infected and vaccinated pigs. Therefore, two kinds of new candidates for oral vaccination have been developed based on the translation of the E2 gene of the SW03 strain, which was isolated from an outbreak of CSF in 2002 in Korea, in transgenic rice calli (TRCs) from Oriza sativa L. cv. Dongjin to express a recombinant E2 protein (rE2-TRCs). The expression of the recombinant E2 protein (rE2) in rE2-TRCs was confirmed using Northern blot, SDS-PAGE, and Western blot analysis. Immune responses to the rE2-TRC in mice and pigs were investigated after oral administration. The administration of rE2-TRCs increased E2-specific antibodies titers and antibody-secreting cells when compared to animals receiving the vector alone (p Pigs receiving rE2-TRCs also showed an increase in IL-8, CCL2, and the CD8+ subpopulation in response to stimulation with prE2. These results suggest that oral administration of rE2-TRCs can induce E2-specific immune responses.

  13. Medium- and long-chain triglycerides labeled with 13C: a comparison of oxidation after oral or parenteral administration in humans.

    Science.gov (United States)

    Metges, C C; Wolfram, G

    1991-01-01

    The special physical properties of medium-chain triglycerides (MCT) result in some substantial differences in their metabolism compared to that of long-chain triglycerides (LCT). Administering MCT is of importance in enteral nutrition of patients with disturbances of fat digestion or lipoprotein lipase deficiency. Their use in parenteral nutrition is also of interest. The purpose of this study was to compare the rate of conversion of MCT and LCT to CO2 after parenteral or oral administration in humans. At 1-wk intervals, a liquid formula diet (418 kJ/h for 8 h) was given to five healthy volunteers following an overnight fast. Two hours after starting this, they were given either 100 mg [13C]trioctanoate or [13C]trioleate orally or parenterally. Excess 13C in breath carbon dioxide was analyzed by mass-spectrometry, and oxidation rates over 7.5 h were calculated. Oxidation rates for [13C]trioctanoate were on the average 34.7% after enteral and 31.0% after parenteral administration, and for [13C]trioleate, 25.3 and 24.9%, respectively (p less than 0.05, trioctanoate vs. trioleate). The results show that the oxidation of trioctanoate in healthy humans is greater both after oral and parenteral administration and increases more rapidly than that of [13C]trioleate.

  14. Pharmacokinetic study of schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B in rat plasma after oral administration of Shengmaisan formula by UPLC-MS.

    Science.gov (United States)

    Sun, Hui; Wu, Fangfang; Zhang, Aihua; Wei, Wenfeng; Han, Ying; Wang, Xijun

    2013-02-01

    Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of cardiovascular diseases in Asia. Its lignans are major components responsible for therapeutic action. A rapid and specific UPLC-Q-TOF/MS has been developed and validated for simultaneous quantification of the five main bioactive components, i.e. schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B, in rat plasma after oral administration of SMS. All calibration curves showed excellent linearity within the test ranges. Validation proved the repeatability of the method was good and recovery was satisfactory. The separation of these compounds was carried out on a Waters ACQUITY HSS T(3) column (2.1 × 100 mm, 1.8 μm) by linear gradient elution using a mobile phase consisting of 0.01% formic acid in water and ACN containing 0.01% formic acid. In this work, plasma pharmacokinetic characteristics of lignans components after oral administration SMS were investigated using UPLC-Q-TOF/MS method. MS was performed on a Waters Micromass high-definition technology with an ESI source. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 6.1. Results demonstrated that the proposed UPLC-Q-TOF/MS method was successfully applied to pharmacokinetic study of all components in rat plasma after oral administration of the SMS.

  15. Antiulcer Activity after Oral Administration of the Wormwood Ethanol Extract on Lesions due to Leishmania major Parasites in BALB/C Mice

    Directory of Open Access Journals (Sweden)

    Kourosh Azizi, Fatemeh Shahidi-Hakak Mohammad Djaefar Moemenbellah-Fard,\tQasem Asgari,\tSoliman Mohammadi-Samani

    2016-04-01

    Full Text Available Herbal extracts were used to investigate the in vivo efficacy of Artemisia absinthium on the treatment of cutaneous leishmaniasis in susceptible mice. A total of 40 BALB/c mice were subjected to assays. In each, 3-5×103 amastigotes of standard Leishmania major strain were inoculated subcutaneously into the tail base of mice. Groups of mice were assigned as: I-negative control, II-positive control, III-Glucantime®, IV-ointment twice a day, V-ointment with oral medicine, VI-oral medicine on parasite injection, VII-oral medicine once ulcer develops, and VIII-ointment-based crème on ulcer. The gold standard of clinical infection control was based on ulcer size measurement using a Vernier scale weekly during 4 weeks Post-Ulcer Development (PUD. The mean ulcer sizes in different groups were compared using the post hoc Dunnett's 3 statistical analyses. There was a significant difference between the two groups of ointment with medicine (V and medicine on parasite inoculation (VI (P ≤ 0.027. Antiulcer activity and healing was noted after oral treatment with aqueous extract on parasite injection. There was a significant difference between data from positive control group and local ointment with oral medicine (P ≤ 0.045 indicating that ointment use facilitated ulcer growth. There was also a significant difference between data from Glucantime® use and ointment with medicine group (P ≤ 0.039 which showed the deteriorating effect of oil-based ointment use. The oral administration of extract had an effect similar to Glucantime® use and led to the repair of ulcer. A. absinthium extract as oral feeder appeared to cause modulation of host responses, ulcer size reduction and tissue repair.

  16. Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

    Directory of Open Access Journals (Sweden)

    Yoleima Lozada

    2012-04-01

    Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

  17. Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation.

    Science.gov (United States)

    Odore, R; De Marco, M; Gasco, L; Rotolo, L; Meucci, V; Palatucci, A T; Rubino, V; Ruggiero, G; Canello, S; Guidetti, G; Centenaro, S; Quarantelli, A; Terrazzano, G; Schiavone, A

    2015-08-01

    Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-day-old broiler chickens were randomly allotted into 2 groups (control and treated animals). OTC (40 mg/kg BW) was administered via drinking water during the 1 to 5 and 20 to 25 days of life periods. At the end of the trial, the birds were slaughtered and the OTC residues in the target tissues were measured by means of liquid chromatography (LC) - tandem mass spectrometry (MS/MS). Cytotoxicity was assessed by evaluating the pro-apoptotic effect of the bone residues on the K562 erythroleukemic line and on the peripheral blood mononuclear cells (PBMC). In all the animals, the OTC residues in the muscle were far below the established MRL of 100 μg/kg. The OTC levels in the bones of the treated animals were instead found in the parts per million (ppm) range. Cell cytotoxicity was assessed by evaluating the pro-apoptotic effect of OTC bone residues on the haematopoietic cell system. This in vitro system has revealed a significant pro-apoptotic effect on both the K562 cell line and PBMC cultures. This result suggests potential human and animal health risks due to the entry of tetracycline residues contained in the bones of treated livestock into the food-chain. This could be of concern, particularly for canine and feline diets, as meat, bone meal, and poultry by-products represent some of the main ingredients of pet foods, especially in the case of dry pet food. Further studies are needed to define the underlying mechanisms of cytotoxicity and to evaluate the in vivo toxicological

  18. Effect of oral administration of Propionibacterium acnes on growth performance, DTH response and anti-OVA titers in goat kids

    Directory of Open Access Journals (Sweden)

    Luis Miguel Ferrer

    2013-01-01

    Full Text Available Immunostimulants are susbstances that stimuli the response of effector cells to activate the immune response such as antigen uptake, cytokine release or antibody response. These substances can increase resistence to infection by different types of microorganisms, reducing dependence of antibiotics used in livestock animals. Recent reports have demonstrated the positive effect of Propionibacterium acnes (P. acnes to control animal diseases. In this study, we evaluated the effect of the non-specific immunostimulant P. acnes on immunological functions and growth performance in goat kids. Twenty five goat kids served as control group (A and another 25 animals received P. acnes being the experimental group (B. Kids were challenged with ovalbumin (OVA to assess humoral immunity. To assess in vivo cell immunity, delayed type hypersensitivity (DTH test with phytohemagglutinin (PHA was used, clinical signs and body weight were recorded each week until 9 weeks of age when the experiment ended. Blood samples were obtained to analyze serum proteins fractions and anti-OVA specific antibodies. No clinical signs of disease and no differences (p>0.05 on body weight between groups were recorded (7.32±0.81 kg in group A, 7.13±0.65 kg in group B. Goat kids from group B had more total protein (59.8±5g/l and albumin levels (32.8±3.3g/l than goat kids from group A (56.6±5.7 g/l, 29.6±3.9 g/l respectively (p<0.05. DTH response in goat kids from group B on day 42 was higher (p<0.05 than group A. At day 63, goat kids from group receiving P. acnes had higher percentage (85.4 of anti-OVA IgM titers (p<0.05 than control group (57.7. In conclusion, the results showed that oral administration of P. acnes to goat kids improved some aspects of the immune system of the animals and it could be used to control goat diseases.

  19. Alginate Microencapsulation for Oral Immunisation of Finfish: Release Characteristics, Ex Vivo Intestinal Uptake and In Vivo Administration in Atlantic Salmon, Salmo salar L.

    Science.gov (United States)

    Ghosh, Bikramjit; Nowak, Barbara F; Bridle, Andrew R

    2015-12-01

    This study examined the feasibility of alginate microcapsules manufactured using a low-impact technology and reagents to protect orally delivered immunogens for use as immunoprophylactics for fish. Physical characteristics and protein release kinetics of the microcapsules were examined at different pH and temperature levels using a microencapsulated model protein, bovine serum albumin (BSA). Impact of the microencapsulation process on contents was determined by analysing change in bioactivity of microencapsulated lysozyme. Feasibility of the method for oral immunoprophylaxis of finfish was assessed using FITC-labelled microcapsules. These were applied to distal intestinal explants of Atlantic salmon (Salmo salar) to investigate uptake ex vivo. Systemic distribution of microcapsules was investigated by oral administration of FITC-labelled microcapsules to Atlantic salmon fry by incorporating into feed. The microcapsules produced were structurally robust and retained surface integrity, with a modal size distribution of 250-750 nm and a tendency to aggregate. Entrapment efficiency of microencapsulation was 51.2 % for BSA and 43.2 % in the case of lysozyme. Microcapsules demonstrated controlled release of protein, which increased with increasing pH or temperature, and the process had no significant negative effect on bioactivity of lysozyme. Uptake of fluorescent-labelled microcapsules was clearly demonstrated by intestinal explants over a 24-h period. Evidence of microcapsules was found in the intestine, spleen, kidney and liver of fry following oral administration. Amenability of the microcapsules to intestinal uptake and distribution reinforced the strong potential for use of this microencapsulation method in oral immunoprophylaxis of finfish using sensitive immunogenic substances.

  20. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    Science.gov (United States)

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  1. Experimental study on the effect of oral meloxicam administration in sows on pre-weaning mortality and growth and immunoglobulin G transfer to piglets.

    Science.gov (United States)

    Mainau, Eva; Temple, Déborah; Manteca, Xavier

    2016-04-01

    Parturation is an intrinsically risky and painful process for both the sow and the piglets that can cause welfare and economic problems. Non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to partially alleviate inflammation and pain after farrowing in sows. NSAIDs effects on piglet mortality and performance show discrepancies and no previous studies have investigated the underlying mechanism. The effects of oral meloxicam treatment to sows on immunoglobulin G (IgG) transfer to piglets around farrowing were investigated. A total of 30 multiparous sows were randomly treated with either oral meloxicam or a mock administration as control group. Treatment was administered as soon as possible at the beginning of the farrowing. A total of 325 piglets were individually weighed at farrowing (day 0) and at weaning (day +21) and piglet mortality was registered during lactation. Four piglets per sow (two piglets suckling from anterior teats and two piglets suckling from posterior teats) were selected for blood sampling at day +1, day +2 and day +20 for IgG analyses. Oral meloxicam treatment to sows significantly increased weight at weaning (mean±SE: 6563±86.3g from oral meloxicam group and 6145±103.2g from control group; P=0.0017) and ADG (mean±SE: 236±3.4g/day from oral meloxicam group and 217±4.5g/day from control group; Pmeloxicam group and 6.8% from control group; P=0.89). IgG levels in piglets from the sows treated with oral meloxicam were significantly higher than the control group at day +1 (mean; median [95% CI] for median=31.9; 31.7 [29.6-33.6] vs. 27.9; 26.8 [25.9-28.3] mg/ml, P=0.0013) and day +2 (27.6; 27.0 [24.8-29.6] vs. 24.5; 24.2 [22.1-25.3] mg/ml, P=0.01). However, at day +20, IgG level in piglet serum was not significantly affected by the treatment (7.6; 7.6 [6.7-8.4] vs. 7.1; 6.9 [6.4-7.3] mg/ml, P=0.59). The administration of meloxicam orally at the beginning of the farrowing in multiparous sows increased the concentration of IgG in

  2. Oral Administration of Bovine Milk from Cows Hyperimmunized with Intestinal Bacterin Stimulates Lamina Propria T Lymphocytes to Produce Th1-Biased Cytokines in Mice

    Directory of Open Access Journals (Sweden)

    Yuanyuan Wang

    2014-03-01

    Full Text Available The goal of this study was to examine the effects of oral administration of bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk “Sustaina” on mucosal immunity in the intestine of adult mice. C57BL/6 mice were orally given immune or control milk for two weeks, and then lymphocyte population and the cytokine production in lamina propria of colon in normal mice and mice induced colitis by dextran sulphate sodium (DSS were detected. We found that the levels of IFN-γ and IL-10 increased, but the levels of IL-17A and IL-4, decreased in lamina propria of colon in immune milk-fed mice as compared with those in control milk-fed mice. Interestingly, oral administration of immune milk partially improved the acute colitis induced by DSS. The levels of TNF-α and IFN-γ increased, but IL-6, IL-17A and IL-4 decreased in lamina propria (LP of colon in immune milk-fed mice with DSS-induced colitis. Our results suggest that immune milk may stimulate CD4+ T cells to polarize towards a Th1 type response, but contrarily suppress Th17 and Th2 cells responses in large intestinal LP of mice. The results indicate that this kind of immune milk has is able to promote the maintainance of intestinal homeostasis and enhance protection against infection, and could alleviate the symptoms of acute colitis in mice.

  3. [The effect of oral administration of roxatidine acetate hydrochloride 3 hours prior to the operation on pH and volume of gastric juice].

    Science.gov (United States)

    Kojima, A; Andoh, K; Shima, T; Koga, Y; Hashimoto, Y

    1991-03-01

    The effect of roxatidine acetate hydrochloride, administered 3 hours prior to induction of anesthesia, on pH and volume of gastric juice was investigated in preoperative patients. In fifty patients, who were scheduled to undergo elective surgery, 150 mg of roxatidine acetate hydrochloride was administered orally 3 hours before the induction of anesthesia. The volume and pH of gastric juice were measured immediately after the induction of anesthesia. In 46 patients out of fifty, pH of gastric juice was more than 2.5, and its volume was below 25 ml. In another 4 patients, pH of gastric juice was more than 2.5, or its volume below 25 ml. We conclude that, oral administration of 150 mg roxatidine 3 hours preoperatively could be effective for the prevention of an aspiration pneumonitis.

  4. Effects of oral powder electrolyte administration on packed cell volume, plasma chemistry parameters, and incidence of colic in horses participating in a 6-day 162-km trail ride.

    Science.gov (United States)

    Walker, Wade T; Callan, Robert J; Hill, Ashley E; Tisher, Kelly B

    2014-08-01

    This study evaluated the effects of administering oral powder electrolytes on packed cell volume (PCV), plasma chemistry parameters, and incidence of colic in horses participating on a 6-day 162-km trail ride in which water was not offered ad libitum. Twenty-three horses received grain with powder electrolytes daily while 19 control horses received grain only. Horses were ridden approximately 32 km a day at a walk or trot. Packed cell volume and plasma chemistry parameters were analyzed daily. Episodes of colic were diagnosed and treated by a veterinarian unaware of treatment group allocation. Blood parameters and incidence of colic were compared between treatment groups. Electrolyte administration did not alter PCV or plasma chemistry parameters compared to controls. The incidence of colic was significantly higher in treated horses (P = 0.05). Oral powder electrolytes did not enhance hydration status or electrolyte homeostasis and may be associated with colic in horses participating on long distance trail rides similar to this model.

  5. Protection and systemic translocation of siRNA following oral administration of chitosan/siRNA nanoparticles

    DEFF Research Database (Denmark)

    Gonzalez, Borja Ballarin; Dagnæs-Hansen, Frederik; Fenton, Robert A.

    2013-01-01

    , gastrointestinal (GI) deposition, and translocation into peripheral tissue of nonmodified siRNA after oral gavage of chitosan/siRNA nanoparticles in mice. In contrast to naked siRNA, retained structural integrity and deposition in the stomach, proximal and distal small intestine, and colon was observed at 1 and 5...... hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ...

  6. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

    Science.gov (United States)

    Katsanou, Efrosini S; Kyriakopoulou, Katerina; Emmanouil, Christina; Fokialakis, Nikolas; Skaltsounis, Alexios-Leandros; Machera, Kyriaki

    2014-01-01

    Chios mastic gum (CMG), a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE), at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD). The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE.

  7. Modulation of CYP1A1 and CYP1A2 hepatic enzymes after oral administration of Chios mastic gum to male Wistar rats.

    Directory of Open Access Journals (Sweden)

    Efrosini S Katsanou

    Full Text Available Chios mastic gum (CMG, a resin derived from Pistacia lentiscus var. chia, is known since ancient times for its pharmacological activities. CYP1A1 and CYP1A2 enzymes are among the most involved in the biotransformation of chemicals and the metabolic activation of pro-carcinogens. Previous studies referring to the modulation of these enzymes by CMG have revealed findings of unclear biological and toxicological significance. For this purpose, the modulation of CYP1A1 and CYP1A2 enzymes in the liver of male Wistar rats following oral administration of CMG extract (CMGE, at the levels of mRNA and CYP1A1 enzyme activity, was compared to respective enzyme modulation following oral administration of a well-known bioactive natural product, caffeine, as control compound known to involve hepatic enzymes in its metabolism. mRNA levels of Cyp1a1 and Cyp1a2 were measured by reverse transcription real-time polymerase chain reaction and their relative quantification was calculated. CYP1A1 enzyme induction was measured through the activity of ethoxyresorufin-O-deethylase (EROD. The results indicated that administration of CMGE at the recommended pharmaceutical dose does not induce significant transcriptional modulation of Cyp1a1/2 and subsequent enzyme activity induction of CYP1A1 while effects of the same order of magnitude were observed in the same test system following the administration of caffeine at the mean daily consumed levels. The outcome of this study further confirms the lack of any toxicological or biological significance of the specific findings on liver following the administration of CMGE.

  8. Effect of administration of oral contraceptives on the synthesis and breakdown of myofibrillar proteins in young women

    DEFF Research Database (Denmark)

    Hansen, M; Langberg, H.; Holm, Lars;

    2011-01-01

    Oral contraceptive (OC) treatment has an inhibiting effect on protein synthesis in tendon and muscle connective tissue. We aimed to investigate whether OC influence myofibrillar protein turnover in young women. OC-users (24±2 years; Lindynette® n=7, Cilest® n=4) and non-OC-users (controls, 24...

  9. Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Christensen, N J; Sørensen, T I;

    1991-01-01

    Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80...

  10. Effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Zhang; Yi-Shi Xing; Meng-Jia Cui; Zeng-Yue Yang

    2016-01-01

    Objective:To study the effect of oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy on the postoperative recurrence and malignant degree of superficial bladder cancer.Methods:A total of 102 patients with superficial bladder cancer who received transurethral resection of bladder tumor in our hospital between April 2012 and April 2015 were selected and randomly divided into combined group who received postoperative oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy and routine group who received postoperative bladder perfusion chemotherapy, the postoperative tumor recurrence was followed up for 3 years, and the levels of tumor markers in serum as well as the expression levels of stem cell marker molecules and immunoregulation molecules in peripheral blood and recurrent lesions were determined.Results: Postoperative 1-year recurrence rate and postoperative 3-year recurrence rate of combined treatment group were significantly lower than those of routine group, and the mean recurrence time was significantly longer than that of routine group; 1 year after operation, serum VEGF, αFGF,βFGF, MMP2 and MMP9 levels were significantly lower than those of routine group, and ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those of routine group; after tumor recurrence, ALDH1, Sox2, Nanog, CD47, CD133, B7-H1, PD-1 and PD-L1 mRNA levels in recurrent lesions of combined treatment group were significantly lower than those of routine group.Conclusion:Oral administration of Shiquandabu pill combined with bladder perfusion chemotherapy has better effect on preventing postoperative recurrence of superficial bladder cancer than bladder perfusion chemotherapy alone, and it has regulating effect on tumor load, characteristics of stem cells and immune response after transurethral resection of bladder tumor.

  11. Effects of the oral administration of viable and heat-killed Streptococcus bovis HC5 cells to pre-sensitized BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Aline D Paiva

    Full Text Available Antimicrobial peptides have been suggested as an alternative to classical antibiotics in livestock production and bacteriocin-producing bacteria could be added to animal feeds to deliver bacteriocins in the gastrointestinal (GI tract of ruminant and monogastric animals. In this study, viable (V and heat-killed (HK Streptococcus bovis HC5 cells were orally administered to pre-sensitized mice in order to assess the effects of a bacteriocin-producing bacteria on histological parameters and the immune response of the GI tract of monogastric animals. The administration of V and HK S. bovis HC5 cells during 58 days to BALB/c mice did not affect weight gain, but an increase in gut permeability was detected in animals receiving the HK cells. Viable and heat killed cells caused similar morphological alterations in the GI tract of the animals, but the most prominent effects were detected in the small intestine. The oral administration of S. bovis HC5 also influenced cytokine production in the small intestine, and the immune-mediated activity differed between V and HK cells. The relative expression of IL-12 and INF-γ was significantly higher in the small intestine of mice treated with V cells, while an increase in IL-5, IL-13 and TNF-α expression was only detected in mice treated with HK cells. Considering that even under a condition of severe challenge (pre-sensitization followed by daily exposure to the same bacterial immunogen the general health of the animals was maintained, it appears that oral administration of S. bovis HC5 cells could be a useful route to deliver bacteriocin in the GI tract of livestock animals.

  12. Toxicological Evaluation of Oral Administration of Phoenix dactylifera L. Fruit Extract on the Histology of the Liver and Kidney of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Abel Nosereme Agbon

    2014-06-01

    Full Text Available Various parts of Phoenix dactylifera (date palm are used in traditional medicine to treat various disorders such as fever, abdominal troubles, etc., in different parts of the world. A preliminary phytochemical screening of the aqueous fruit extract of Phoenix dactylifera (AFPD revealed the presence of alkaloids, tannins, saponins, flavonoids and carbohydrates. This study was designed to investigate the effects of oral administration of AFPD on the histology of the liver and kidney in Wistar rats. Thirty-nine Wistar rats were divided into two groups-control (three rats and treatment (thirty-six rats. The animals in experimental group were further categorised for two phase study (eighteen rats divided into three groups; six rats/group for each phase. In the first phase, the three groups (A, B and C were administered AFPD (10, 100 and 1000 mg/kg, oral, respectively. In the second phase, the three groups (D, E and F were administered AFPD (1600, 2900 and 5000 mg/kg, oral, respectively. In both phases, after 24 h of AFPD administration, three rats of the six in each group were sacrificed and the other three sacrificed after 21 days. Histopathological examinations of liver and kidney sections of the experimental animals were compared with the control. No mortality or signs of toxicity was observed in the experimental animals upon administration of AFPD, even at doses as high as 5000 mg/kg, which was confirmed by mild pathological changes with remarkable recovery after 21 days. This result demonstrates that the LD50 of AFPD is greater than 5000 mg/kg and is relatively safe.

  13. Changes in Renal Function Following Administration of Oral Sodium Phosphate or Polyethylene Glycol for Colon Cleansing before Colonoscopy

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    Ramy Abaskharoun

    2007-01-01

    Full Text Available Changes in renal function were compared in patients receiving oral sodium phosphate (NaP for colon cleansing and those receiving large-volume polyethylene glycol (PEG solution to determine whether oral NaP resulted in frequent renal damage that had gone clinically undetected. From 1995 to 2004, a cohort of consecutive patients who had serum creatinine (Cr drawn immediately before colonoscopy and again after subsequent procedures three months to nine years later (almost 80% of patients between the first and fifth year were identified. Chronic renal failure (CRF was defined as an abnormal Cr at repeat measurement or an abnormal Cr clearance as estimated by the Cockroft-Gault equation at the time of repeat Cr measurement. Medications and medical comorbid conditions were recorded. Seven hundred sixty-seven patients (51% female and 49% male; 81% oral NaP and 19% PEG with normal baseline Cr levels were identified through the endoscopy unit database at the Hotel Dieu Hospital, Queen’s University (Kingston, Ontario. Of these, 55 (7% developed CRF. Forty-two (6.8% patients receiving oral NaP developed renal failure compared with 13 patients (8.7% receiving PEG (Fisher’s exact test; P=0.382, but the magnitude of CRF was small in each group (Cr level lower than 160 μmol/L. Using logistic regression analysis with the choice of preparation, medications and medical comorbid conditions as independent variables, only age and blood pressure were predictive of the development of renal failure (P=0.014 and P=0.001, respectively. Baseline Cr clearance was similiar in both the NaP and PEG groups and the absolute difference after colonoscopy did not differ. The present study concluded that the ingestion of oral NaP for colon cleansing before colonoscopy did not result in frequent renal damage that went clinically undetected.

  14. Oral administration of heat-inactivated Mycobacterium bovis reduces the response of farmed red deer to avian and bovine tuberculin.

    Science.gov (United States)

    López, Vladimir; González-Barrio, David; Lima-Barbero, José Francisco; Ortiz, José Antonio; Domínguez, Lucas; Juste, Ramón; Garrido, Joseba M; Sevilla, Iker A; Alberdi, Pilar; de la Fuente, José; Gortázar, Christian

    2016-04-01

    Orally delivered mycobacterial antigens may not sensitize the immunized animals causing a positive tuberculin skin test response. As the first step to address this critical issue, we characterized the response of farmed red deer (Cervus elaphus) to orally delivered heat-inactivated Mycobacterium bovis. Thirty-two adult red deer hinds from a farm known to be free of tuberculosis (TB) were randomly assigned to two different treatment groups, immunized (n=24) and control (n=8). Immunized hinds were dosed orally with 2 ml of PBS containing 6 × 10(6) heat-inactivated M. bovis. The mean skin test response of immunized deer to both avian purified protein derivative (aPPD) and bovine PPD (bPPD) was consistently lower in immunized than in control hinds. One year after immunization, immunized hinds had a significant reduction in the skin test response to aPPD and in the ELISA antibody levels against both aPPD and bPPD (24-36% reduction; P<0.05). By contrast, no significant change was observed in the skin test response to phytohaemagglutinin, or in the ELISA antibody levels against the M. bovis specific antigen MPB70. The mRNA levels for C3, IFN-γ and IL-1β and serum protein levels for IFN-γ and IL-1β did not vary between immunized and control deer. However, serum C3 protein levels were significantly higher (P=0.001) in immunized than in control deer six months after immunization. These results confirm that oral heat-inactivated M. bovis does not sensitize farmed red deer and therefore does not cause false-positive responses in the tuberculin skin test. The absence of sensitization in orally immunized deer opens the possibility of testing the vaccine in deer and possibly other ruminants without the risk of causing false-positive reactions in TB-tests. This study also provided the first evidence that orally-delivered inactivated mycobacterial antigens elicit some kind of immune response in a ruminant.

  15. Augmentation of the antibody response of Atlantic salmon by oral administration of alginate-encapsulated IPNV antigens.

    Directory of Open Access Journals (Sweden)

    Lihan Chen

    Full Text Available The objective of the present study was to assess the effect of alginate-encapsulated infectious pancreatic necrosis virus antigens in inducing the immune response of Atlantic salmon as booster vaccines. One year after intraperitoneal injection with an oil-adjuvanted vaccine, post-smolts were orally boosted either by 1 alginate-encapsulated IPNV antigens (ENCAP; 2 soluble antigens (UNENCAP or 3 untreated feed (control. This was done twice, seven weeks apart. Sampling was done twice, firstly at 7 weeks post 1st oral boost and the 2nd, at 4 weeks after the 2nd oral boost. Samples included serum, head kidney, spleen and hindgut. Serum antibodies were analyzed by ELISA while tissues were used to assess the expression of IgM, IgT, CD4, GATA3, FOXP3, TGF-β and IL-10 genes by quantitative PCR. Compared to controls, fish fed with ENCAP had a significant increase (p<0.04 in serum antibodies following the 1st boost but not after the 2nd boost. This coincided with significant up-regulation of CD4 and GATA3 genes. In contrast, serum antibodies in the UNENCAP group decreased both after the 1st and 2nd oral boosts. This was associated with significant up-regulation of FOXP3, TGF-β and IL-10 genes. The expression of IgT was not induced in the hindgut after the 1st oral boost but was significantly up-regulated following the 2nd one. CD4 and GATA3 mRNA expressions exhibited a similar pattern to IgT in the hindgut. IgM mRNA expression on the other hand was not differentially regulated at any of the times examined. Our findings suggest that 1 Parenteral prime with oil-adjuvanted vaccines followed by oral boost with ENCAP results in augmentation of the systemic immune response; 2 Symmetrical prime and boost (mucosal with ENCAP results in augmentation of mucosal immune response and 3 Symmetrical priming and boosting (mucosal with soluble antigens results in the induction of systemic immune tolerance.

  16. The comparative pharmacokinetics of two pyrrolizidine alkaloids, senecionine and adonifoline, and their main metabolites in rats after intravenous and oral administration by UPLC/ESIMS.

    Science.gov (United States)

    Wang, Changhong; Li, Yan; Gao, Jiangguo; He, Yuqi; Xiong, Aizhen; Yang, Li; Cheng, Xuemei; Ma, Yueming; Wang, Zhengtao

    2011-07-01

    Pyrrolizidine alkaloids (PAs) are considered to be one of the most hepatotoxic groups of compounds of plant origin and are present in about 3% of the world's flowering plants. Most PAs represent a considerable health hazard to both livestock and humans through the consumption of plants and PA-contaminated products such as milk, honey, herbal teas, and medicines. This study determined the differences in the in vivo pharmacokinetic behavior of senecionine (SEN), adonifoline (ADO), and their main metabolites in rats after intravenous administration and oral administration by ultraperformance liquid chromatography/electrospray ionization mass spectrometry. Upon intravenous administration and oral administration of SEN and ADO, significant differences in pharmacokinetics were observed, with the SEN and ADO being absorbed fast with lower bioavailability and being quickly metabolized to PA N-oxides and hydroxylation products of PAs or their N-oxides. It could be seen that the plasma concentration ratio of senecionine N-oxide (SEN-NO) to SEN (C (SEN-NO)/C (SEN)) was significantly larger than that for adonifoline N-oxide (ADO-NO) and ADO (C (ADO-NO)/C (ADO)) (P < 0.001) for both dosing routes in rats. The high N-oxygenation activity and extensive toxicity of SEN, compared with ADO, in rats raised the question of whether or not the higher metabolic rate of SEN in rats in vivo was related to its potent toxicity. The toxicity of SEN-NO and ADO-NO needs to be evaluated further and compared in vitro/in vivo. This study was most helpful for interpreting the metabolism of metabolic bioactivation and detoxication, and toxicity differences among SEN, ADO and other PAs.

  17. Comparing the Effects of Yoga & Oral Calcium Administration in Alleviating Symptoms of Premenstrual Syndrome in Medical Undergraduates

    OpenAIRE

    Mehta Bharati

    2016-01-01

    Introduction: Medical undergraduates are heavily burdened by their curriculum. The females, in addition, suffer from vivid affective or somatic premenstrual syndrome (PMS) symptoms such as bloating, mastalgia, insomnia, fatigue, mood swings, irritability, and depression. The present study was proposed to attenuate the symptoms of PMS by simple lifestyle measures like yoga and/or oral calcium. Methods: 65 medical female students (18-22 years) with a...

  18. Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

    Institute of Scientific and Technical Information of China (English)

    罗维丹; 邬成霖

    2001-01-01

    @@ Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

  19. Oral Administration of Surface-Deacetylated Chitin Nanofibers and Chitosan Inhibit 5-Fluorouracil-Induced Intestinal Mucositis in Mice

    Science.gov (United States)

    Koizumi, Ryo; Azuma, Kazuo; Izawa, Hironori; Morimoto, Minoru; Ochi, Kosuke; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Ito, Norihiko; Okamoto, Yoshiharu; Saimoto, Hiroyuki; Ifuku, Shinsuke

    2017-01-01

    This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs. PMID:28134832

  20. SYSTEMES POLYMERIQUES A BASE DE DISPERSION AQUEUSE ADMINISTRES PAR VOIE ORALE POUR LA LIBERATION CONTROLEE DU PRINCIPE ACTIF

    OpenAIRE

    Yang, Qiaowen

    2009-01-01

    In this study, we are interested in coatings of multiparticulate oral dosage forms for controlled drug delivery. Aqueous polymer dispersions are of steadily increasing importance for the development of controlled release dosage forms due to safety and environmental concerns related to the use of organic solvents. However, the film formation mechanisms are more complex and storage stability may be difficult to achieve. A thermal post-treatment (curing) is generally required to enhance the degr...

  1. Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats.

    Science.gov (United States)

    Wickham, Robert J; Park, Jinwoo; Nunes, Eric J; Addy, Nii A

    2015-08-12

    Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique with high spatial and temporal (sub-second) resolution that has been utilized to examine phasic DA release in several types of preparations. In vitro experiments in single-cells and brain slices and in vivo experiments in anesthetized rodents have been used to identify mechanisms that mediate dopamine release and uptake under normal conditions and in disease models. Over the last 20 years, in vivo FSCV experiments in awake, freely moving rodents have also provided insight of dopaminergic mechanisms in reward processing and reward learning. One major advantage of the awake, freely moving preparation is the ability to examine rapid DA fluctuations that are time-locked to specific behavioral events or to reward or cue presentation. However, one limitation of combined behavior and voltammetry experiments is the difficulty of dissociating DA effects that are specific to primary rewarding or aversive stimuli from co-occurring DA fluctuations that mediate reward-directed or other motor behaviors. Here, we describe a combined method using in vivo FSCV and intra-oral infusion in an awake rat to directly investigate DA responses to oral tastants. In these experiments, oral tastants are infused directly to the palate of the rat--bypassing reward-directed behavior and voluntary drinking behavior--allowing for direct examination of DA responses to tastant stimuli.

  2. Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration.

    Science.gov (United States)

    Harde, Harshad; Siddhapura, Krupa; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-06-20

    The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan-glucomannan nanoassemblies (sCh-GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh-GM-NAs exhibited ~152 nm particle size and ~85% EE of both the toxoids. The lyophilized sCh-GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh-GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh-GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh-GM-NAs posed significantly (p<0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1 IU/mL) antibodies. Importantly, commercial 'Dual antigen' vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh-GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization.

  3. Influence of body condition on plasma prednisolone and prednisone concentrations in clinically healthy cats after single oral dose administration.

    Science.gov (United States)

    Center, Sharon A; Randolph, John F; Warner, Karen L; Simpson, Kenneth W; Rishniw, Mark

    2013-08-01

    Influence of body condition (over-conditioned vs. normal-conditioned) on plasma glucocorticoid concentrations after single dose oral prednisolone or prednisone in 11 cats (5 normal-conditioned and 6-over-conditioned) was investigated using a two-drug crossover trial (3-week washout interval). Body condition was determined using criterion-referenced bioelectrical impedance together with plasma drug concentrations (prednisolone [active drug] and prednisone [pro-drug]) measured by HPLC. Although interconversion of each drug to the other was confirmed, a single 2mg/kg body weight oral dose of prednisolone produced significantly higher plasma prednisolone concentration (∼4-fold higher AUC) compared to prednisone. Significantly higher plasma drug concentrations in over-conditioned cats (∼2-fold) compared to normal-conditioned cats might explain their perceived increased risk for glucocorticoid associated side effects (hepatic lipidosis, diabetes mellitus). Findings suggest low comparative bioavailability of oral prednisone compared to prednisolone in cats and consideration of lean body mass or ideal body weight for dosing practices.

  4. Evaluation and improvement of the properties of the novel cystine-knot microprotein McoEeTI for oral administration.

    Science.gov (United States)

    Werle, M; Kafedjiiski, K; Kolmar, H; Bernkop-Schnürch, A

    2007-03-06

    Cystine-knot microproteins exhibit several properties that make them highly interesting as scaffolds for oral peptide drug delivery. It was therefore the aim of the study to evaluate the novel clinically relevant cystine-knot microprotein McoEeTI regarding its potential for oral delivery. Additionally, based on the gained results, important features of McoEeTI were improved. Enzymatic degradation was caused by chymotrypsin, trypsin and porcine small intestinal juice whereas McoEeTI was stable towards elastase, membrane bound proteases, pepsin and porcine gastric juice. Only minor McoEeTI degradation was observed during a 24h incubation period in rat plasma. In the presence of various physiological ions about 50% of McoEeTI formed di- and/or trimers. P(app) value of McoEeTI was determined to be (7.4+/-0.4)x10(-6)cm/s. Sodium caprate and polycarbophil-cysteine (PCP-Cys) had no beneficial effect on McoEeTI permeation, whereas the utilization of a chitosan-thiobutylamidine (Chito-TBA) system improved McoEeTI permeation 3-fold. Enzymatic stability could be strongly improved by the utilization of Bowman-Birk-Inhibitor (BBI) as well as PCP-Cys. In conclusion, this study indicates that McoEeTI represents a promising candidate as a novel scaffold for oral peptide drug delivery.

  5. 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

    PURPOSE: This study evaluated the effect of corticosteroid (CS) administration on edema, analgesia, and neuroregeneration in conjunction with surgical dental extraction, orthognathic surgery, and the risk of developing side effects. MATERIALS AND METHODS: A systematic search of the literature...

  6. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shannon D Shields

    Full Text Available Cerebellar symptoms significantly diminish quality of life in patients with multiple sclerosis (MS. We previously showed that sodium channel Nav1.8, although normally restricted to peripheral somatosensory neurons, is upregulated in the cerebellum in MS, and that Nav1.8 expression is linked to ataxia and MS-like symptoms in mice. Furthermore, intracerebroventricular administration of the Nav1.8 blocker A-803467 temporarily reversed electrophysiological and behavioral manifestations of disease in a mouse MS model; unfortunately A-803467 is not orally bioavailable, diminishing the potential for translation to human patients. In the present study, we assessed the effect of per os (p.o. dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE model. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders.

  7. Detection and Quantification of Flavobacterium psychrophilum-Specific Bacteriophages In Vivo in Rainbow Trout upon Oral Administration: Implications for Disease Control in Aquaculture

    Science.gov (United States)

    Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias; Lauritsen, Anne H.

    2014-01-01

    The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods—bath, oral intubation into the stomach, and phage-coated feed—with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼105 PFU mg intestine−1 and ∼103 PFU mg spleen−1 within the first 24 h following the bath and ∼107 PFU mg intestine−1 and ∼104 PFU mg spleen−1 within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼104 PFU mg intestine−1 and ∼101 PFU mg spleen−1 were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60% survival

  8. Detection and quantification of Flavobacterium psychrophilum-specific bacteriophages in vivo in rainbow trout upon oral administration: implications for disease control in aquaculture.

    Science.gov (United States)

    Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Middelboe, Mathias; Lauritsen, Anne H; Madsen, Lone

    2014-12-01

    The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods-bath, oral intubation into the stomach, and phage-coated feed-with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10(5) PFU mg intestine(-1) and ∼10(3) PFU mg spleen(-1) within the first 24 h following the bath and ∼10(7) PFU mg intestine(-1) and ∼10(4) PFU mg spleen(-1) within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10(4) PFU mg intestine(-1) and ∼10(1) PFU mg spleen(-1) were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60

  9. Oral Administration of Faecalibacterium prausnitzii Decreased the Incidence of Severe Diarrhea and Related Mortality Rate and Increased Weight Gain in Preweaned Dairy Heifers.

    Directory of Open Access Journals (Sweden)

    Carla Foditsch

    Full Text Available Probiotics are a promising alternative to improve food animal productivity and health. However, scientific evidence that specific microbes can be used to benefit animal health and performance is limited. The objective of this study was to evaluate the effects of administering a live culture of Faecalibacterium prausnitzii to newborn dairy calves on subsequent growth, health, and fecal microbiome. Initially, a safety trial was conducted using 30 newborn bull calves to assess potential adverse effects of the oral and rectal administration of F. prausnitzii to neonatal calves. No adverse reactions, such as increased body temperature or heart and respiratory rates, were observed after the administration of the treatments. All calves survived the experimental period, and there was no difference in fecal consistency score, attitude, appetite or dehydration between the treatment groups. The rectal route was not an efficient practice while the oral route ensures that the full dose is administered to the treated calves. Subsequently, a randomized field trial was completed in a commercial farm with preweaned calves. A total of 554 Holstein heifers were assigned to one of two treatment groups: treated calves (FPTRT and non-treated calves (control. Treated calves received two oral doses of F. prausnitzii, one at treatment assignment (1st week and another one week later. The FPTRT group presented significantly lower incidence of severe diarrhea (3.1% compared with the control group (6.8%. Treated calves also had lower mortality rate associated with severe diarrhea (1.5% compared to control calves (4.4%. Furthermore, FPTRT calves gained significantly more weight, 4.4 kg over the preweaning period, than controls calves. The relative abundance of F. prausnitzii in the fecal microbiota was significantly higher in the 3rd and 5th weeks of life of FPTRT calves than of the control calves, as revealed by sequencing of the 16S rRNA gene. Our findings showed that oral

  10. Hydrolysis is the dominating in vivo metabolism pathway for arctigenin: identification of novel metabolites of arctigenin by LC/MS/MS after oral administration in rats.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2013-04-01

    The phenylpropanoid dibenzylbutyrolactone lignan arctigenin, a key component found in Arctium lappa, or burdock, has been reported with a variety of therapeutic effects including anticancer, anti-inflammation, and antivirus effects. Using LC/MS/MS, three novel metabolites of arctigenin, namely, arctigenic acid, arctigenin-4-O'-glucuronide, and 4-O-demethylarctigenin were identified after oral administration of arctigenin in rats for the first time. Another potential metabolite of arctigenin, arctigenin-4'-O-sulfate, was identified in vitro but not in vivo. Structure of arctigenic acid, the major metabolite of arctigenin, was confirmed by 13C-NMR and 1H-NMR. Rapid hydrolysis in plasma was identified as the major metabolic pathway of arctigenin after its oral administration, with Vmax, Km, and Clint in rat plasma determined to be 2.21 ± 0.12 nmol/min/mg, 89.12 ± 9.44 µM, and 24.74 µL/min/mg, respectively. Paraoxonase 1 was further confirmed to be the enzyme responsible for arctigenin hydrolysis, with Vmax, Km, and Clint determined to be 55.39 ± 1.49 nmol/min/mg, 300.3 ± 10.86 µM, and 184.45 µL/min/mg, respectively.

  11. Simultaneous determination of catechin, epicatechin and epicatechin gallate in rat plasma by LC-ESI-MS/MS for pharmacokinetic studies after oral administration of Cynomorium songaricum extract.

    Science.gov (United States)

    Zhang, Qiu-Hong; Wang, Wen-Biao; Li, Jin; Chang, Yan-Xu; Wang, Yue-Fei; Zhang, Jishu; Zhang, Bo-Li; Gao, Xiu-Mei

    2012-01-01

    A rapid and valid method was developed for simultaneous determination catechin, epicatechin and epicatechin gallate in rat plasmas using scopoletin (103 ng mL(-1)) as an internal standard (IS). The separation was performed on Eclipse plus C18 column (100 mm × 4.6 mm, 1.8 μm) at a flow rate of 0.3 mL min(-1), and acetonitrile-0.1% formic acid was used as mobile phase. The recoveries of three analytes and IS were more than 78.9%. The lower limits of quantitation (LLOQ) in rat plasma were 2.14, 2.38 and 2.08 ng mL(-1) respectively for catechin, epicatechin and epicatechin gallate. Intra-day and inter-day precisions were within 12%. The accuracies were more than 85%. After single oral administration of 15.25 g kg(-1) Cynomorium songaricum extract, C(max) of catechin, epicatechin and epicatechin gallate in rat plasma were respectively 86.69±38.65, 32.57±15.00 and 36.93±12.62 ng mL(-1) while T(max) values were respectively 0.15±0.09, 0.20±0.10 and 0.20±0.13 h. The results demonstrated that the present LC-MS/MS method was sensitive enough for pharmacokinetic study of catichins following oral administration of C. songaricum extract.

  12. Cloud point extraction-HPLC method for the determination and pharmacokinetic study of aristolochic acids in rat plasma after oral administration of Aristolochiae Fructus.

    Science.gov (United States)

    Ren, Gang; Huang, Qun; Wu, Jiangang; Yuan, Jinbin; Yang, Gaihong; Yan, Zhihong; Yao, Shouzhuo

    2014-03-15

    Based on cloud-point extraction (CPE), a high performance liquid chromatography method (HPLC) was developed and validated for the determination of aristolochic acids (AAs) in rat plasma after oral administration of Aristolochiae Fructus (AF). Non-ionic surfactant Genapol X-080, an environmentally friendly solvent, was used for the micelle-mediated extraction. Various influencing factors on CPE process were investigated and optimized. AAs were extracted from rat plasma after adding 1ml of 4.5% (v/v) surfactant in the presence of 0.2mol/l HCl and 20mg NaCl, and the incubation temperature and time were 50°C and 10min, respectively. Base-line separation was obtained for the AAs in rat plasma with the optimized chromatography conditions. The detection limits (LOD) reached downward 10ng/ml. The intra-day and inter-day precisions were less than 7.8%, the accuracies were within ±5.5%, and the average recovery factors were in the range of 94.5-105.4%. In comparison with liquid-liquid extraction, the CPE method has a considerable LOD and higher recoveries. The proposed CPE-HPLC method was specific, sensitive and reliable, and could be an effective tool for the determination of AAs in biological matrixes. With the method the pharmacokinetics of AAs were investigated successfully after oral administration of AF by rats.

  13. Ultra-performance liquid-chromatography with tandem mass spectrometry for rapid analysis of pharmacokinetics, biodistribution and excretion of schisandrin after oral administration of Shengmaisan.

    Science.gov (United States)

    Lu, Sheng-Wen; Zhang, Ai-Hua; Sun, Hui; Yan, Guang-Li; Han, Ying; Wu, Xiu-Hong; Wang, Xi-Jun

    2013-12-01

    This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component-schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC-MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/z 415.22 → 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half-life (T1/2 ) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin was recovered in feces and was not detected in urine.

  14. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY.

  15. The effects of oral administration of Yunnan Baiyao on blood coagulation in beagle dogs as measured by kaolin-activated thromboelastography and buccal mucosal bleeding times.

    Science.gov (United States)

    Frederick, Jami; Boysen, Søren; Wagg, Catherine; Chalhoub, Serge

    2017-01-01

    We examined the effects of oral administration of Yunnan Baiyao (YB) on hemostasis by measuring buccal mucosal bleeding times (BMBTs) and doing citrated kaolin-activated whole-blood thromboelastography (TEG). In a randomized controlled crossover trial 8 beagle dogs were given either placebo or 1000 mg of YB orally every 12 h for 5 consecutive treatments. Blood was drawn 24 h before treatment and 2 and 24 h after the last treatment, and the BMBT was measured in each sample in duplicate. The TEG analysis was done in duplicate 60 ± 5 min after sample collection. There were no adverse effects of treatment and no significant differences between the control and treatment BMBTs or TEG parameters at any time point. Significant differences were found between baseline and 24 h after the last treatment within the treatment group for the TEG parameters LY30 and LY60 and within the control group for the TEG parameters MA, G, LY30, and LY60. Thus, at the dose and frequency of administration in this study YB did not appear to have any clinically significant effects on the measured coagulation parameters. The differences within the treatment group were likely due to analytic error since similar differences were seen in the control group. Further studies with a larger sample, as well as more direct measures of platelet function, are needed.

  16. The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

    Science.gov (United States)

    Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

    2016-03-24

    In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

  17. Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

    Directory of Open Access Journals (Sweden)

    Yoshiharu Okamoto

    2012-10-01

    Full Text Available We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa, intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa and high-molecular-weight fucoidan (HMWF: 300–330 kDa. The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet. The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

  18. Bifidobacterium animalis subsp. lactis BB-12 administration in early childhood: a randomized clinical trial of effects on oral colonization by mutans streptococci and the probiotic.

    Science.gov (United States)

    Taipale, T; Pienihäkkinen, K; Salminen, S; Jokela, J; Söderling, E

    2012-01-01

    A randomized clinical trial studied the effects of early administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on oral colonization of (1) mutans streptococci (MS), and (2) BB-12. In this double-blind, placebo-controlled study, infants (n = 106) received probiotic bacteria (BB-12 group), xylitol (X group), or sorbitol (S group). Test tablets were administered twice a day (from the age of 1-2 months) with a novel slow-release pacifier or a spoon (daily dose of BB-12 10(10) CFU, polyol 200-600 mg). Samples were collected from mucosa/teeth at the age of 8 months and 2 years for BB- 12 determination (qPCR) and plate culturing of MS (MSB, TYCSB), lactobacilli (Rogosa) and yeasts (Sabouraud). The MS levels of the mothers were determined (Dentocult SM Strip Mutans). The baseline characteristics of the three groups were similar. Mean duration of tablet delivery was 14.9 ± 6.7 months. In all groups, >90% of the mothers showed high MS counts (log CFU ≥5). MS colonization percentages of the children at the age of 2 years were rather low (BB-12 group: 6%; X group: 31%; S group: 10%; p < 0.05). The levels of lactobacilli and yeasts did not differ between the groups. BB-12 cell counts barely exceeding the detection limit were found in three of the oral samples of the 8-month-old children; however, the 2-year samples did not contain BB-12. The early administration of BB-12 did not result in permanent oral colonization of this probiotic or significantly affect MS colonization in the children.

  19. Effect of submucosal or oral administration of prednisolone on postoperative sequelae following surgical extraction of impacted mandibular third molar: A randomized controlled study

    Science.gov (United States)

    Ibikunle, Adebayo Aremu; Adeyemo, Wasiu Lanre; Ladeinde, Akinola Ladipo

    2016-01-01

    Background: The aim of the study was to evaluate the effect of preoperatively administered submucosal and oral prednisolone on postoperative pain, facial swelling, and trismus following third molar surgery. Patients and Methods: This was a randomized controlled trial in which subjects were randomly distributed into three groups. Group A consisted of subjects who received 40 mg oral prednisolone; Group B consisted of subjects who received 40 mg submucosal injection of prednisolone while Group C consisted of subjects who did not receive prednisolone. Each group had 62 subjects. Measurements for facial width/facial swelling, pain, and mouth opening were recorded preoperatively and postoperatively. The postoperative evaluation points were postoperative days 1, 3, and 7. These measurements were compared with the preoperative values both within and among the groups. Results: Most of the subjects were in their third decade of life. A considerable increase in the mean postoperative values for pain, facial width and trismus was observed. Notably, subjects who did not receive prednisolone showed comparatively higher values for the measured parameters throughout the postoperative evaluation period. Subjects who received submucosal injection of prednisolone showed overall lower values compared to those who received oral prednisolone. Conclusion: The results of this study indicate that the administration of prednisolone has a significantly beneficial effect in ameliorating the postoperative sequelae of the third molar surgery. In addition, the effect of submucosally injected prednisolone is comparable to the orally administered prednisolone; indeed it shows superiority to the latter in a number of dimensions. Submucosal injection of prednisolone offers a simple, effective, easy, safe, and minimally invasive option to existing therapeutic methods of reducing these postoperative sequelae. PMID:27833246

  20. Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice

    Directory of Open Access Journals (Sweden)

    Paula eCardona

    2016-01-01

    Full Text Available Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression towards active tuberculosis (TB lesions in a human-like murine model using C3HeB/FeJ mice. In the present study, we studied the effect of different treatment schedules with heat-killed non-tuberculous-mycobacteria (NTM species when given orally, based on the hypothesis of generating oral tolerance. This study included M. manresensis, a new species belonging to the fortuitum group, present in drinking water. Oral treatment with M. manresensis for two weeks was able to induce a PPD-specific Tregs population, which has been related to a decrease in the neutrophilic infiltration found in TB lesions. Further mechanistic analysis using PPD-stimulated splenocytes links this two-week treatment with heat-killed M. manresensis to IL-10 production and memory PPD-specific Tregs, and also to a weak PPD-specific global immune response stimulation, increasing IL-6, TNF and IFN-γ production. In lungs, this treatment decreased the bacillary load, granulomatous infiltration and pro-inflammatory cytokines (TNF, IFN-γ, IL-6 and IL-17. Oral administration of M. manresensis during standard treatment for TB also significantly reduced the relapse of active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB treatment. This supports the usefulness of generating a new kind of protection based on a complex balanced immune response focused on both destroying the bacilli and including control of an excessive inflammatory response.

  1. Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Christensen, N J; Sørensen, T I;

    1991-01-01

    Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80...... values (all p less than 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p less than 0.01; and +93%, p less than 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p less than 0.01), whereas...

  2. Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: combined administration of BSH and BPA.

    Science.gov (United States)

    Garabalino, Marcela A; Heber, Elisa M; Monti Hughes, Andrea; Pozzi, Emiliano C C; Molinari, Ana J; Nigg, David W; Bauer, William; Trivillin, Verónica A; Schwint, Amanda E

    2014-06-01

    Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70-85ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.

  3. 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

    included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m.......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...

  4. Hidratación oral continua o a dosis fraccionadas en niños deshidratados por diarrea aguda Oral rehydration in continuous administration or in fractionated doses in dehydrated children with acute diarrhea

    Directory of Open Access Journals (Sweden)

    Felipe Mota-Hernández

    2002-01-01

    Full Text Available Objetivo. Evaluar la seguridad y efectividad de dos técnicas de hidratación oral. Material y métodos. Ensayo clínico aleatorio, hecho en el Servicio de Hidratación Oral del Hospital Infantil de México, Federico Gómez, entre septiembre de 1998 y junio de 1999. Cuarenta pacientes deshidratados por diarrea aguda, menores de cinco años, recibieron suero oral ad libitum (grupo AL y otros cuarenta lo recibieron en dosis fraccionada (grupo DF. Las características clínicas fueron similares en ambos grupos. Los resultados se presentan como promedio y desviación estándar o mediana, según la distribución de frecuencias simples y relativas. Resultados. El promedio de gasto fecal en el grupo AL fue 11.0±7.5 g/kg/h y en el grupo DF 7.1±7.4 (p=0.03. La ingesta de suero, el tiempo de hidratación y la diuresis promedio, fueron similares entre ambos grupos (p>0.05. Seis pacientes del grupo AL y cinco del DF tuvieron gasto fecal alto (>10 g/kg/hora, mejorando con la administración de atole de arroz. Un paciente del grupo AL y dos pacientes del DF tuvieron vómitos persistentes, mejorando con gastroclisis. Ningún paciente requirió rehidratación intravenosa. Conclusiones. Estos resultados sugieren que la administración de suero oral ad libitum, bajo supervisión, es tan segura y efectiva como la técnica de dosis fraccionada para el tratamiento de niños deshidratados por diarrea aguda.Objective. To evaluate the safety and effectiveness of two oral rehydration techniques. Material and Methods. A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS ad libitum (AL group; another forty patients received ORS in fractionated doses (FD group. Clinical characteristics were similar in both groups. Results are presented as

  5. Human radiation studies: Remembering the early years. Oral history of Donner Lab Administrator Baird G. Whaley, August 15, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Baird G. Whaley, Donner Lab Administrator, was interviewed by representatives of US DOE Office of Human Radiation Experiments (OHRE). The purpose of the interview was to capture the remembrances of Mr. Whaley concerning what he could relate on activities at the Donner Lab that pertain to the OHRE responsibilities. Following a brief biographical sketch, Mr. Whaley relates his experiences in administration at the LAB including funding activities, staffing concerns, intralaboraory politics, and remembrances of John Lawrence, John Gofman, Cornelius Tobias, Jim Born, Alex Margolis, B.V.A. Low- Beer, and Ed Alpen. Further patient care procedures for Donner Clinic Research Programs were discussed.

  6. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.

  7. Comparing the Effects of Yoga & Oral Calcium Administration in Alleviating Symptoms of Premenstrual Syndrome in Medical Undergraduates

    Directory of Open Access Journals (Sweden)

    Mehta Bharati

    2016-09-01

    Full Text Available Introduction: Medical undergraduates are heavily burdened by their curriculum. The females, in addition, suffer from vivid affective or somatic premenstrual syndrome (PMS symptoms such as bloating, mastalgia, insomnia, fatigue, mood swings, irritability, and depression. The present study was proposed to attenuate the symptoms of PMS by simple lifestyle measures like yoga and/or oral calcium. Methods: 65 medical female students (18-22 years with a regular menstrual cycle were asked to self-rate their symptoms, along with their severity, in a validated questionnaire for two consecutive menstrual cycles. Fifty-eight students were found to have PMS. Twenty girls were given yoga training (45 minutes daily, five days a week, for three months. Another group of 20 was given oral tablets of calcium carbonate daily (500 mg, for three months and rest 18 girl served as control group. Data were analyzed by SPSS ver.13 software. Results: The yoga and calcium groups showed a significant decrease in number and severity of premenstrual symptoms whereas in the control group there was not the significant difference. Conclusion: Encouraging a regular practice of yoga or taking a tablet of calcium daily in the medical schools can decrease the symptoms of premenstrual syndrome.

  8. Comparing the Effects of Yoga & Oral Calcium Administration in Alleviating Symptoms of Premenstrual Syndrome in Medical Undergraduates.

    Science.gov (United States)

    Bharati, Mehta

    2016-09-01

    Introduction: Medical undergraduates are heavily burdened by their curriculum. The females, in addition, suffer from vivid affective or somatic premenstrual syndrome (PMS) symptoms such as bloating, mastalgia, insomnia, fatigue, mood swings, irritability, and depression. The present study was proposed to attenuate the symptoms of PMS by simple lifestyle measures like yoga and/or oral calcium. Methods: 65 medical female students (18-22 years) with a regular menstrual cycle were asked to self-rate their symptoms, along with their severity, in a validated questionnaire for two consecutive menstrual cycles. Fifty-eight students were found to have PMS. Twenty girls were given yoga training (45 minutes daily, five days a week, for three months). Another group of 20 was given oral tablets of calcium carbonate daily (500 mg, for three months) and rest 18 girl served as control group. Data were analyzed by SPSS ver.13 software. Results: The yoga and calcium groups showed a significant decrease in number and severity of premenstrual symptoms whereas in the control group there was not the significant difference. Conclusion: Encouraging a regular practice of yoga or taking a tablet of calcium daily in the medical schools can decrease the symptoms of premenstrual syndrome.

  9. Role of sodium silicate in induction of scleroderma-related autoantibodies in brown Norway rats through oral and subcutaneous administration.

    Science.gov (United States)

    Al-Mogairen, Sultan M

    2011-05-01

    Silica hazard is a growing occupational problem and has been reported to be associated with scleroderma via case reports and occupational studies. The aim of this study is to demonstrate whether oral or subcutaneous silicate exposure can induce an autoimmunity and scleroderma susceptibility in immunosensitive rats. Sodium silicate in a dose of 3 mg in 0.2 ml NS was administered through oral and subcutaneous routes to 20 brown Norway rats. Autoantibodies including ANA, anti-RNP, anti-SCL70 and anti-centromere were measured and compared with pre- and post-challenge serum samples. Serum ANA and anti-RNP were high in significant number of rats (P < 0.05) of only the subcutaneous silicate group. There is an increase in the number of positive readings of autoantibodies at 14th week in comparison with the number of positive readings of autoantibodies at 7th week but P values were not significant. It may be concluded that silicate might induce autoimmunity and scleroderma and it seems to be that the longer the duration of exposure the greater the risk. This is probably the first experimental animal study demonstrating the induction of scleroderma-related autoantibodies after challenge with silicate.

  10. A STUDY ON PREVENTION OF VITAMIN A DEFICIENCY BY ANNUAL ORAL MASSIVE DOSE VITAMIN A AND E EMULSION ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    Darwin Karyadi

    2012-09-01

    Full Text Available Suatu penyelidikan mengenai pencegahan dan pengobatan penyakit defisiensi vit. A. di Cibatok, Bogor, telah dilakukan dengan menggunakan oral massive dose vit. A. (retinol palmitat e 300,000 I.U. dikombinasikan dengan vit E (a tocopherol acetate 50 I.U. dl. Dua group anak-anak umur 1-6 tahun dipilih masing-masing sebagai group Experiment dan Control yang hanya diberikan placebo. Sedangkan masing-masing group dibagi lagi menjadi golongan-golongan penderita dan golongan Non vit. A. defisiensi (normal. Ternyata setelah 6 (enam bulan kemudian 90 percent penderita yang mendapat pengobatan menjadi sembuh dan sebaliknya 88.9 percent dari penderita yang mendapat placebo masih tetap menderita defisiensi vit. A. (table 2 Table 3. Menunjukkan adanya pengaruh penyakit infeksi G.I tract terhadap berhasilnya pengobatan dan juga pada umumnya dapat disimpulkan bahwa gizi penderita tidak mempengaruhi pengobatan. Table 4 Kadar Vit. A. didalam darah penderita setelah pengobatan ternyata jauh lebih tinggi dari semula. Sedangkan dalam group yang mendapat placebo tidak terjadi kenaikan. Dari data penyelidikan tersebut dapat disimpulkan bahwa pemberian oral massive dose kombinasi dari vit. A dan E pada anak-anak sebelum sekolah dapat mencegah, mengobati gejala-gejala defisiensi vit. A. di mata.

  11. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice.

    Science.gov (United States)

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg((-1)) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg((-1)) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  12. Dietary geraniol by oral or enema administration strongly reduces dysbiosis and systemic inflammation in dextran sulphate sodium-treated mice.

    Directory of Open Access Journals (Sweden)

    Luigia eDe Fazio

    2016-03-01

    Full Text Available (Trans-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH, is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulphate sodium (DSS-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120mg kg(-1 body weight, starting six days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg(-1 dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2 expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  13. Effect of intravenous or oral sodium chlorate administration on the fecal shedding of Escherichia coli in sheep

    Science.gov (United States)

    The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 +/- 2.5 kg) were administered 150 mg NaClO3 per kg BW by gavage or i.v. infusion in a cross-over design with sal...

  14. Biokinetics of (13)C in the human body after oral administration of (13)C-labeled glucose as an index for the biokinetics of (14)C.

    Science.gov (United States)

    Masuda, Tsuyoshi; Tako, Yasuhiro; Matsushita, Kensaku; Takeda, Hiroshi; Endo, Masahiro; Nakamura, Yuji; Hisamatsu, Shun'ichi

    2016-09-01

    The retention of (13)C in the human body after oral administration of (13)C-labeled glucose was studied in three healthy volunteer subjects to estimate the 50 year cumulative body burden for (13)C as an index of the committed dose of the radioisotope (14)C. After administration of (13)C-labeled glucose, the volunteers ingested controlled diets with a fixed number of calories for 112 d. Samples of breath and urine were collected up to 112 d after administration. Samples of feces were collected up to 14 d after administration. Hair samples were obtained at 119 d after administration and analyzed as a representative index of the rate of excretion of organic (13)C via pathways such as skin cell exfoliation and mucus secretion. All samples were analyzed for (13)C/(12)C atomic ratio to determine the rate of excretion via each pathway. We then constructed a metabolic model with a total of four pathways (breath, urine, feces, and other) comprising seven compartments. We determined the values of the biokinetic parameters in the model by using the obtained excretion data. From 74% to 94% of the (13)C administered was excreted in breath, whereas    0.1). In addition, the dataset for one of the three subjects was markedly different from those of the other two. When we estimated the 50 year cumulative body burden for (13)C by using our model and we included non-statistically significant parameters, a considerable cumulative body burden was found in the compartments excreting to the other pathway. Although our results on the cumulative body burden of (13)C from orally administered carbon as glucose were inconclusive, we found that the compartments excreting to the other pathway had a markedly long residence time and therefore should be studied further to clarify the fate of carbon in the human body. In addition to excreta, data for serum and blood cell samples were also collected from the subjects to examine the metabolism of (13)C in human body.

  15. Ultra-performance liquid chromatography-tandem mass spectrometry determination and depletion profile of flunixin residues in tissues after single oral administration in rabbits.

    Science.gov (United States)

    Zhu, Ai-Ling; Peng, Tao; Liu, Liang; Xia, Xi; Hu, Ting; Tao, Xiao-Qi; Wen, Kai; Cheng, Lin-Li; Li, Jian-Cheng; Ding, Shuang-Yang; Cao, Xing-Yuan; Jiang, Hai-Yang

    2013-09-01

    An ultra-performance liquid chromatography with tandem mass spectrometric detection (UPLC-MS/MS) method was developed for the detection of flunixin residues in rabbit tissues. The samples were extracted with acidic acetonitrile, defatted with n-hexane, and then purified by HLB solid-phase extraction cartridge. Analysis was carried out on UPLC-ESI-MS/MS working with multiple reaction monitoring (MRM) mode. The limits of detection (LODs) of the method were 0.3-0.8μgkg(-1) and limits of quantification (LOQs) were 1.0-3.0μgkg(-1) in rabbit tissues, respectively. In all fortified samples at a concentration range of 1.0-300.0μgkg(-1), mean recoveries were 61.7-115.7% with relative standard deviations (RSDs) below 16%. Residue depletion of flunixin in rabbit was conducted after oral administration at a dose of 5mgkg(-1) of body weight. The average concentrations for flunixin measured 2h post-administration in kidney and intestine were significantly higher than in liver, heart and muscle. The concentrations for flunixin in all rabbit tissues were below the LOD or not detected in all tissues after 96h administration of drug. A minimum withdrawal time of 21h was indicated for residue levels in heart, liver, kidney, intestine and muscle below the maximum residue limits (MRLs).

  16. Excretion of 3-Mercaptolactate-Cysteine Disulfide, Sulfate and Taurine in human Urine before and after Oral Administration of Sulfur-containing Amino Acids.

    Directory of Open Access Journals (Sweden)

    Yuasa,Shigeki

    1990-06-01

    Full Text Available The excretion of 3-mercaptolactate-cysteine mixed disulfide [S-(2-hydroxy-2-carboxyethylthio-L-cysteine, HCETC], sulfate and taurine in the urine of normal adults was investigated before and after oral administration of L-cysteine and related sulfur-containing amino acids. Before the loading of amino acids, the excretion (mean +/- SD per kg of body weight per day of HCETC, free sulfate and taurine was 0.096 +/- 0.042, 305.7 +/- 66.1 and 31.9 +/- 8.7 mumols, respectively. After the loading of L-cysteine (800 mumols/kg of body weight, the average excretion in the 24-h urine of HCETC increased 2-fold and that of taurine increased 1.6-fold. The average excretion of free sulfate after the L-cysteine loading was 989.4 +/- 145.1 and 388.8 +/- 51.6 mumols/kg per day in the first and second 24-h urine, respectively, indicating that the sulfur corresponding to 85% of the L-cysteine loaded was excreted as free sulfate in 24 h. Administration of L-cystine (400 mumols/kg resulted in similar results. The increase in HCETC after L-cysteine or L-cystine administration indicates that L-cysteine is metabolized in part through the transamination pathway (3-mercaptopyruvate pathway and that an equilibrium exists between the intake and excretion of sulfur in humans.

  17. Toxicity effect of sub-chronic oral administration of class bitters® - a polyherbal formula on serum electrolytes and hematological indices in male Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Kingsley C. Patrick-Iwuanyanwu

    2015-11-01

    Full Text Available The indiscriminate administration of readyto- use herbal formulations has become a major concern due to their potential health risk. The study investigated the effect of class bitters® (CB - a polyherbal formula prepared with Mondia whitei, Khaya senegalensis, Capparis erythrocarpus, Thoningia sanguinea and Xylopia aethiopica on serum electrolytes and hematological parameters in male Wistar albino rats. Two doses (500 and 1000 mg kg–1 of the polyherbal drugs were administered orally to male Wistar albino rats for a period of 9 weeks. The results showed that administration of 500 and 1000 mg kg–1 body weight of CB recorded a marked increase in the levels of sodium and chlorum when compared with control. However, there was a marked reduction in the levels of potassium and hydrogen carbonate. The results of the study also showed a significant (P≤0.05 decrease in the level of hematological parameters such as hemoglobin (Hb, packed cell volume (PCV, red blood cells (RBCs and platelets levels in the male Wistar albino rats, when compared with control. The marked decrease in Hb, PCV, RBCs and platelets concentrations observed in experimental rats in this study suggest that CB may have an adverse effect on erythropoiesis. These observations therefore showed that long-term administration of CB might cause renal disease and anemia.

  18. Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial.

    Science.gov (United States)

    de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

    2015-01-01

    The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18-50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN.

  19. Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.

    Science.gov (United States)

    Thompson, G A; St Peter, J V; Heise, M A; Horowitz, Z D; Salyers, G C; Charles, T T; Brezovic, C; Russell, D A; Skare, J A; Powell, J H

    1996-11-01

    The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.

  20. Prophylaxis of tumor through oral administration of IL-12 GM-CSF gene carried by live attenuated salmonella

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A live attenuated AraA- autotrophic mutant of Salmonella typhimurium (SL3261) was used as carrier for eukaryotic expression vectors EGFPN1, pCMVmIL-12, pCMVhIL-12, pCMVmGM-CSF and pCMVhGM-CSF and was administered orally to BALB/c and C57BL/6 mice. After 6 weeks, these mice were challenged with 4T1 and Lewis tumor cells respectively. GFP expression and gene integrati-on could be detected in mice's livers, spleens, intestines, kidneys and tumors. The serum level of cytokines increased significantly in treated mice, so did the ratio of , which resulted in the tumor regression and prolongation of the survival time of those mice. These researches laid an experimental foundation for the tumor gene therapy using live attenuated salmonella.

  1. Toxic influence of chronic oral administration of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice

    Institute of Scientific and Technical Information of China (English)

    REN Jin-peng; ZHAO Yu-wu; SUN Xiao-jiang

    2009-01-01

    Background Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice. Methods A total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry, mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique. Results Locomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.

  2. 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

  3. Thiolated polycarbophil/glutathione: defining its potential as a permeation enhancer for oral drug administration in comparison to sodium caprate.

    Science.gov (United States)

    Perera, Glen; Barthelmes, Jan; Vetter, Anja; Krieg, Christof; Uhlschmied, Cindy; Bonn, Günther K; Bernkop-Schnürch, Andreas

    2011-08-01

    Thiolated polyacrylates were shown to be permeation enhancers with notable potential. The aim of this study was to evaluate the permeation enhancing properties of a thiolated polycarbophil/glutathione (PCP-Cys/GSH) system for oral drug application in comparison to a well-established permeation enhancer, namely sodium caprate. In vitro permeation studies were conducted in Ussing-type chambers with sodium fluoresceine (NaFlu) and fluoresceine isothiocyanate labeled dextran (molecular mass 4 kDa; FD4) as model compounds. Bioavailability studies were carried out in Sprague Dawley rats with various formulations. Moreover, cytotoxic effects of both permeation enhancers were compared. Permeation enhancement ratios of 1% sodium caprate were found to be 3.0 (FD4) and 2.3 (NaFlu), whereas 1% PCP-Cys/0.5% GSH displayed enhancement ratios of 2.4 and 2.2. Both excipients performed at a similar level in vivo. Sodium caprate solutions increased oral bioavailability 2.2-fold (FD4) and 2.3-fold (NaFlu), while PCP-Cys hydrogels led to a 3.2-fold and 2.2-fold enhancement. Cell viability experiments revealed a significantly higher tolerance of Caco-2 cells towards 0.5% PCP-Cys (81% survival) compared to 0.5% sodium caprate (5%). As PCP-Cys is not absorbed from mucosal membranes due to its comparatively high molecular mass, systemic side-effects can be excluded. In conclusion, both systems displayed a similar potency for permeation enhancement of hydrophilic compounds. However, PCP-Cys seems to be less harmful to cultured cells.

  4. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice

    OpenAIRE

    ORIKASA, Shuzo; NABESHIMA, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (109 CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of ky...

  5. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

    OpenAIRE

    Shin Chang-Sik; Jung Donald; Borghini-Fuhrer Isabelle; Duparc Stephan; Morris Carrie A; Fleckenstein Lawrence

    2011-01-01

    Abstract Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), ...

  6. The antioxidant status and oxidative stability of muscle from lambs receiving oral administration of Artemisia herba alba and Rosmarinus officinalis essential oils.

    Science.gov (United States)

    Aouadi, Dorra; Luciano, Giuseppe; Vasta, Valentina; Nasri, Saida; Brogna, Daniela M R; Abidi, Sourour; Priolo, Alessandro; Salem, Hichem Ben

    2014-06-01

    The effect of the dietary supplementation to lambs of essential oils (EOs) from rosemary (Rosmarinus officinalis) and artemisia (Artemisia herba alba) on the antioxidant status of muscle and on meat oxidative stability was studied. Eighteen Barbarine lambs were divided into 3 groups and for 95days received oat hay and concentrates. One group (C) was not supplemented, while the other two groups received 400mg/kg of EOs from rosemary (R400) or artemisia (A400). Both EOs possessed antioxidant properties and their oral administration improved the reducing and radical scavenging capacity of the muscle compared to the C treatment (P<0.01). Nevertheless, supplementing EOs did not exert protection against lipid oxidation and did not affect the colour stability in meat over 7days of aerobic storage.

  7. The Effect of Oral Administration of Fermented Rice by Monascus purpureus JmbA on Blood of Hypercholesterolemia White Mouse (Rattus sp.

    Directory of Open Access Journals (Sweden)

    NOVIK NURHIDAYAT

    2006-10-01

    Full Text Available Fermented rice by Monascus purpureus, namely angkak, produces lovastatin. Lovastatin is believed and studied as anti-hypercholesterolemic agent. Somehow, its effects on blood parameters were less known. Therefore, a study on the effect of angkak on erythrocyte, leukocyte, thrombocyte, and haemoglobin level was conducted, involving 15 male Sprague Dawley strain white mice that were divided into 5 treatment groups. The result showed that oral administration of angkak beared lovastatin to the hipercholesterolemic mice could increase the number of trombocyte during the study. Increasing the number of thrombocyte was different depended on dosage of angkak. The optimum dosage was 0.1 g/day. Angkak could also increase haemoglobin concentration and the number of leucocyte, although that raise did not depend on dosage of angkak. Meanwhile, the number of erythrocyte was not affected by angkak.

  8. Cytoprotective effect of hydroxytyrosyl alkyl ether derivatives after oral administration to rats in a model of glucose-oxygen deprivation in brain slices.

    Science.gov (United States)

    Muñoz-Marín, Javier; De La Cruz, José Pedro; Guerrero, Ana; López-Leiva, Inmaculada; López-Villodres, Juan Antonio; Reyes, José Julio; Espartero, José Luis; Madrona, Andrés; Labajos, María Teresa; González-Correa, José Antonio

    2012-08-08

    This study was designed to determine whether the oral administration of hydroxytyrosol (HT) alkyl ether derivatives has a neuroprotective effect in rats. The animals were treated for 7 days with HT or ethyl, butyl, hexyl, octyl, and dodecyl HT ether. A method of in vitro hypoxia-reoxygenation in brain slices was used. Hexyl, octyl, and dodecyl HT derivatives reduced brain cell death (LDH efflux). Lipid peroxidation and nitrite concentrations were inhibited most by hexyl, octyl, and dodecyl derivatives. Concentrations of 3-nitrotyrosine were reduced by HT butyl, hexyl, octyl, and dodecyl ether derivatives. Interleukin-1β was significantly reduced in brain slices from rats treated with all HT ether derivatives. LDH efflux showed a linear correlation with brain concentrations of lipid peroxides, nitrites plus nitrates, and interleukin 1β. The reduction in oxidative and nitrosative stress and decreased production of pro-inflammatory interleukins may be the basis for the observed neuroprotective effects.

  9. Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs.

    Science.gov (United States)

    Bidgood, T L; Papich, M G

    2005-08-01

    Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.

  10. Oral tylosin administration is associated with an increase of faecal enterococci and lactic acid bacteria in dogs with tylosin-responsive diarrhoea.

    Science.gov (United States)

    Kilpinen, Susanne; Rantala, Merja; Spillmann, Thomas; Björkroth, Johanna; Westermarck, Elias

    2015-09-01

    The term tylosin-responsive diarrhoea (TRD) is used for canine recurrent diarrhoea cases for which no underlying cause can be found after extensive diagnostic investigations, but which show a response to the antibiotic tylosin in a few days. The objective of this prospective, one-arm longitudinal trial was to assess the effects of oral tylosin administration on the faecal levels of potentially probiotic bacteria, such as Enterococcus spp. and lactic acid bacteria (LAB), in dogs with TRD. This trial included 14 client-owned suspected TRD dogs that were on tylosin treatment and had firm faeces. Treatment was then terminated and dogs were followed up for up to 2 months to determine the recurrence of diarrhoea. Once diarrhoea started, dogs received tylosin (orally, 25 mg/kg, once daily for 7 days). At the end of the treatment period, stools were firm again in 11 dogs (TRD dogs); three dogs continued having diarrhoea and were excluded from the study. Faecal samples were collected at all three time-points for culture of LAB and enterococci. In TRD dogs, the colony counts of Enterococcus spp. (P = 0.003), LAB (P = 0.037), tylosin-resistant Enterococcus spp. (P tylosin treatment and had normal faecal consistency compared to when they had diarrhoea following discontinuation of tylosin. In conclusion, cessation of diarrhoea in TRD dogs with tylosin treatment could be mediated by selection of a specific lactic acid population, the Enterococcus spp., due to their potential probiotic properties.

  11. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    Science.gov (United States)

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

  12. In vivo targeted delivery of CD40 shRNA to mouse intestinal dendritic cells by oral administration of recombinant Sacchromyces cerevisiae.

    Science.gov (United States)

    Zhang, L; Zhang, T; Wang, L; Shao, S; Chen, Z; Zhang, Z

    2014-07-01

    Short hairpin RNA (shRNA)-mediated gene regulation is a commonly used technique for gene manipulation. An efficient and safe delivery system is indispensable when shRNA is delivered into living organisms for gene therapy. Previous studies have proved that DNA and protein can be delivered into dendritic cells (DCs) by non-pathogenic Saccharomyces cerevisiae without being degraded. CD40 is closely related to apoptosis of tumor cells and some immune mechanisms. In this study, we demonstrated that recombinant yeast S. cerevisiae efficiently delivered the shRNA of immune-associated gene (CD40) into mouse intestinal DCs via oral administration. Western blot analysis of isolated intestinal DCs indicated that the inhibition of CD40 gene expression reached up to 56-91%. The secretion of cytokines such as interleukin-2 (IL-2), IL-6, IL-10, IL-12, tumor necrosis factor-α and interferon-γ in intestinal DCs had varying degrees of changes. In conclusion, we found that orally administered recombinant yeast can be used as an efficient shRNA delivery system for intestinal DC-specific gene silencing and immunomodulation in vivo.

  13. Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Hung, Cheng-Han; Cheng, Shi-Yann; Chan, Tzu-Min; Lee, Maw-Rong

    2015-09-01

    Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (μElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using μElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction.

  14. [Cytokine secretion in whole blood of healthy subjects following oral administration of Urtica dioica L. plant extract].

    Science.gov (United States)

    Teucher, T; Obertreis, B; Ruttkowski, T; Schmitz, H

    1996-09-01

    Twenty healthy volunteers ingested for 21 days 2 capsules b.i.d. of an IDS 23/1 containing nettle leaf extract (Rheuma-Hek). Before and after 7 and 21 days the basal and the lipopolysaccharide (LPS) stimulated tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) concentrations were measured ex vivo. In vitro the effects of IDS 23/1 on the release of these cytokines were determined. Additionally basal interleukin-4 (IL-4) and interleukin-10 (IL-10) levels were recorded. Orally taken the test drug has ex vivo no effect on basal levels of TNF-alpha, IL-1 beta, IL-4, IL-6 or IL-10 which were always below detection limits. After 7 and 21 days ingestion ex vivo a decrease of LPS stimulated TNF-alpha release of 14.6 and 24.0%, respectively, was observed. IL-1 beta was reduced for 19.2 and 39.3%. In vitro IDS 23/1 added to whole blood resulted in an exceeded inhibition of LPS stimulated TNF-alpha and IL-1 beta secretion which correlated with the duration of the drug ingestion. Using the highest tested IDS 23/1 concentration the inhibition reached 50.5 (day 0) to 79.5% (day 21) for TNF-alpha and 90.0 (day 0) to 99.2% (day 21) for IL-1 beta, respectively. IDS 23/1 induced a pronounced release of IL-6 in absence of LPS only in vitro. The detected IL-6 concentrations were comparable to those after LPS stimulation, additive effects could not be observed. The absence of detectable IL-6 concentrations in whole blood ex vivo after oral ingestion of the tested drug as well as the differences in the inhibition patterns for TNF-alpha and IL-1 beta ex vivo and ex vivo in vitro suggest that the extract contains different pharmacological effective compounds with varying bioavailabilities.

  15. Metabolism and plasma pharmacokinetics of isoorientin, a natural active ingredient, in Sprague-Dawley male rats after oral and intravenous administration.

    Science.gov (United States)

    Shi, Peiying; Lin, Xinhua; Yao, Hong

    2015-01-01

    1. Several pharmacological effects have been revealed on isoorientin, suggesting its potential medicinal prospects. The metabolic and plasma pharmacokinetic profiles of isoorientin were investigated in rats. 2. For intra-gastric gavage, parent drug and three metabolites were detected in urine and feces by HPLC-MS/MS, but only one metabolite was found in plasma and identified as isoorientin 3'- or 4'-O-sulfate (M1) according to MS and UV absorbance spectra. 3. After a single i.v. administration of isoorientin (5, 10, or 15 mg/kg B.W.) in rats, linear pharmacokinetic property was observed with favorable terminal half-lives (1.67 ± 1.32-2.07 ± 0.50 h). After a single p.o. administration of isoorientin (150 mg/kg B.W.) in rats, plasma isoorientin concentration was low, but the concentration of M1 was comparatively high. Low systemic exposure of oral isoorientin in rats could result from its low aqueous solubility and extensive first-pass metabolism, and plasma concentration of M1 can be used as a biomarker of isoorientin intake. Isoorientin showed low oral bioavailability (8.98 ± 1.07%), and had about 6% or 45% dose recovery in urine or feces, respectively, 72 h after intra-gastric gavage. 4. These studies are the first to describe the pharmacokinetics of isoorientin via i.v. or p.o. dosing, providing important information for understanding its process in vivo.

  16. Stereoselective urinary excretion of S-(-)- and R-(+)-propranolol glucuronide following oral administration of RS-propranolol in Chinese Han subjects

    Science.gov (United States)

    Luan, Lian-Jun; Shao, Qing; Ma, Jian-Yin; Zeng, Su

    2005-01-01

    AIM: To study the stereoselectivity of phase II glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7±2.46% and 7.68±1.60% for S-(-)- and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount(Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol. PMID:15793873

  17. Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule.

    Science.gov (United States)

    Xiaowen, Li; Ling, Tong; Yunfei, Li; Guoxiang, Sun; Dailin, Yang; Herry, Sun

    2016-04-01

    An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, α-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG).

  18. Stereoselective urinary excretion of S-(-)- and R-(+)-propranolol glucuronide following oral administration of RS-propranolol in Chinese Han subjects

    Institute of Scientific and Technical Information of China (English)

    Lian-Jun Luan; Qing Shao; Jian-Yin Ma; Su Zeng

    2005-01-01

    AIM: To study the stereoselectivity of phase Ⅱglucuronidation metabolism of side-chain propranolol in Chinese Hah population.METHODS: Sixteen adult Chinese Hah volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC.RESULTS: The mean values of kwere 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7±2.46% and 7.68±1.60% for S-(-)- and R-(+)-propranolol glucuronide,respectively. The results showed the elimination rate constant kof S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide.CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.

  19. Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat

    Energy Technology Data Exchange (ETDEWEB)

    Argiles, J.; Herrera, E.

    1989-02-01

    Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.

  20. Comparison of the effectiveness of oral sildenafil versus oxygen administration as a test for feasibility of operation for patients with secondary pulmonary arterial hypertension.

    Science.gov (United States)

    Ajami, Gholam Hossein; Borzoee, Mohammad; Radvar, Mohammad; Amoozgar, Hamid

    2008-05-01

    It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). In this study we determined the effectiveness of sildenafil and compared its efficacy with inhaled nasal oxygen (O2) during cardiac catheterization in patients with congenital heart diseases (CHD) and PAH, as a test of feasibility for surgical repair of the patients. We studied 15 patients, 9 male and 6 female, with a mean age of 8.3 years. Hemodynamic measurements were made at baseline, after O2 administration for 20 min (5 L/min by mask), and then 45 min after administration of a single dose of sildenafil (0.5 mg/kg orally or via nasogastric tube). Mean PAP at baseline was 72.2 +/- 12.54 mm Hg and was reduced by sildenafil to 52.5 +/- 9.6 and by O2 to 61.3 +/- 10.39. Both sildenafil and O2 decreased PAP effectively (p = 0.08 and p = 0.04, respectively). Pulmonary vascular resistance (PVR) was calculated for 12 patients, with a baseline level of 9.08 +/- 1.09 mm Hg . L(-1) . min, which was significantly decreased by O2, to 3.74 +/- 0.43, and by sildenafil, to 5.93 +/- 0.75 (p = 0.005 and p = 0.05, respectively). Sildenafil, as a single oral dose, can effectively reduce PAP and PVR. This novel PDE5 inhibitor can be used for assessment of feasibility of operation for patients with CHD and PAH when inhaled NO is not available.

  1. LC-MS/MS determination of naringin, hesperidin and neohesperidin in rat serum after orally administrating the decoction of Bulpleurum falcatum L. and Fractus aurantii.

    Science.gov (United States)

    Li, Xiuling; Xiao, Hongbin; Liang, Xinmiao; Shi, Dazhuo; Liu, Jiangang

    2004-01-27

    To identify and quantify biologically active components in rat serum after orally administrating the decoction of Bulpleurum falcatum L. and Fractus aurantii, one of traditional Chinese medicines (TCMs), high-performance liquid chromatography (HPLC)-tandem mass spectrometry method was developed and validated. The HPLC separation was carried out on a Waters Nova Pak C(18) column using acetonitrile and water as mobile phase after the sample of rat serum was cleaned up with solid-phase extraction. Atmospheric pressure chemical ionization in the negative ion mode and selected reaction monitoring (SRM) method was developed to determine the active components. Three flavonoids of hesperidin, neohesperidin and naringin were identified in the serum by comparing their retention times and three independent SRM precursor/product ion transitions with those of corresponding reference standards. The concentrations of naringin, hesperidin and neohesperidin in rat serum determined by SRM measurement were 16.3, 11.9 and 14.3 ng/ml, respectively, after orally administrating the decoction of B. falcatum L. and F. aurantii. This method was validated in terms of recovery, linearity, accuracy and precision (intra- and interday variation). The recoveries from spiked control samples were 93.0, 89.3 and 91.2% for hesperidin, neohesperidin and naringin, respectively. Linearity in rat serum was observed over the range of 2.0-50.0 ng/ml. Percent bias (accuracy) and precision were well within the acceptable range and the relative standard deviation (R.S.D.) of the measured rat serum samples was less than 10% (n=5).

  2. Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enterica serovar Typhimurium infection in mice

    Directory of Open Access Journals (Sweden)

    Perdigón Gabriela

    2011-08-01

    Full Text Available Abstract Background Diarrheal infections caused by Salmonella, are one of the major causes of childhood morbidity and mortality in developing countries. Salmonella causes various diseases that range from mild gastroenteritis to enteric fever, depending on the serovar involved, infective dose, species, age and immune status of the host. Probiotics are proposed as an attractive alternative possibility in the prevention against this pathogen infection. Previously we demonstrated that continuous Lactobacillus casei CRL 431 administration to BALB/c mice before and after challenge with Salmonella enterica serovar Typhimurium (S. Typhimurium decreased the severity of Salmonella infection. The aim of the present work was to deep into the knowledge about how this probiotic bacterium exerts its effect, by assessing its impact on the expression and secretion of pro-inflammatory (TNFα, IFNγ and anti-inflammatory (IL-10 cytokines in the inductor and effector sites of the gut immune response, and analyzing toll-like receptor (TLR2, TLR4, TLR5 and TLR9 expressions in both healthy and infected mice. Results Probiotic administration to healthy mice increased the expression of TLR2, TLR4 and TLR9 and improved the production and secretion of TNFα, IFNγ and IL-10 in the inductor sites of the gut immune response (Peyer's patches. Post infection, the continuous probiotic administration, before and after Salmonella challenge, protected the host by modulating the inflammatory response, mainly in the immune effector site of the gut, decreasing TNFα and increasing IFNγ, IL-6 and IL-10 production in the lamina propria of the small intestine. Conclusions The oral administration of L. casei CRL 431 induces variations in the cytokine profile and in the TLRs expression previous and also after the challenge with S. Typhimurium. These changes show some of the immune mechanisms implicated in the protective effect of this probiotic strain against S. Typhimurium, providing

  3. Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task.

    Science.gov (United States)

    Perez-García, Georgina; Meneses, Alfredo

    2005-07-01

    In this work we aimed to re-examine the 5-HT6 receptor role, by testing the selective antagonists SB-357134 (1-30 mg/kg p.o.) and SB-399885 (1-30 mg/kg p.o.) during memory consolidation of conditioned responses (CR%), in an autoshaping Pavlovian/instrumental learning task. Bioavailability, half-life and minimum effective dose to induce inappetence for SB-357134 were 65%, 3.4 h, and 30 mg/kg p.o., and for SB-399885 were 52%, 2.2 h, and 50 mg/kg p.o., respectively. Oral acute and chronic administration of either SB-357134 or SB-399885 improved memory consolidation compared to control groups. Acute administration of SB-357134, at 1, 3, 10 and 30 mg/kg, produced a CR% inverted-U curve, eliciting the latter dose a 7-fold increase relative to saline group. Acute injection of SB-399885 produced significant CR% increments, being 1 mg/kg the most effective dose. Repeated administration (7 days) of either SB-357134 (10 mg/kg) or SB-399885 (1 mg/kg) elicited the most significant CR% increments. Moreover, modeling the potential therapeutic benefits of 5-HT6 receptor blockade, acute or repeated administration of SB-399885, at 10 mg/kg reversed memory deficits produced by scopolamine or dizocilpine, and SB-357134 (3 and 10 mg/kg) prevented amnesia and even improved performance. These data support the notion that endogenously 5-HT acting, via 5-HT6 receptor, improves memory consolidation.

  4. Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

    Directory of Open Access Journals (Sweden)

    Hyun-moon Back

    2015-01-01

    Full Text Available KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life and Tmax of matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively. Cmax and AUCinf of matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

  5. Significant mucosal sIgA production after a single oral or parenteral administration using in vivo CD40 targeting in the chicken.

    Science.gov (United States)

    Chou, Wen-Ko; Chen, Chang-Hsin; Vuong, Christine N; Abi-Ghanem, Daad; Waghela, Suryakant D; Mwangi, Waithaka; Bielke, Lisa R; Hargis, Billy M; Berghman, Luc R

    2016-10-01

    Many pathogens enter the host through mucosal surfaces and spread rapidly via the circulation. The most effective way to prevent disease is to establish mucosal and systemic immunity against the pathogen. However, current vaccination programs in poultry industry require repeated administrations of live-attenuated virus or large amounts (10 to 100μg) of antigen together with adjuvant to induce specific secretory IgA immune responses at the mucosal effector sites. In the present study, we show that a single administration of 0.4μg of oligopeptide complexed with an agonistic anti-chicken CD40 (chCD40) monoclonal antibody (Mab) effectively targets antigen-presenting cells of the bird's mucosa-associated lymphoid tissue in vivo, and induces peptide-specific secretory IgA (sIgA) in the trachea 7days post administration. Anti-chCD40 Mab-peptide complex was administered once to four-week old male Leghorns via various mucosal routes (orally, via cloacal drinking, or oculo-nasally) or via subcutaneous (s.c.) immunization. Immunization through any of the three mucosal induction routes induced significant peptide-specific mucosal sIgA responses 7 and 14days after immunization. Interestingly, s.c. injection of the complex also induced mucosal sIgA. Our data suggest in vivo targeting of CD40 as a potential adjuvant platform, particularly for the purpose of enhancing and speeding up mucosal vaccine responses in chickens, and potentially other food animals. This is the first study able to elicit specific sIgA immune responses in remote mucosal sites with a single administration of only 0.4μg of antigen.

  6. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

    Science.gov (United States)

    Orikasa, Shuzo; Nabeshima, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-Zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan. These results suggest the potential of BB536 for supplemental treatment of the symptoms of schizophrenia.

  7. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.

  8. Psychomotor slowing, neuroendocrine responses, and behavioral changes after oral administration of meta-chlorophenylpiperazine in normal volunteers.

    Science.gov (United States)

    Sabbe, B; Hulstijn, W; Maes, M; Pier, M; Scharpé, S; Zitman, F

    2001-12-31

    The mixed 5-HT receptor agonist/antagonist meta-chlorophenylpiperazine (mCPP) is known to suppress locomotor activity in mice and rats. This study aimed: (1) to determine whether mCPP induces cognitive and motor changes in normal human volunteers and how these changes relate to the neuroendocrine effects of mCPP; and (2) to compare these cognitive and motor changes to the known cognitive and motor slowing patterns in depression and schizophrenia. A computerized method (used in previous research) analyzed fine motor behavior during figure-copying tasks. In 14 normal male volunteers behavioral responses, body temperature, plasma levels of prolactin and cortisol, and cognitive and motor performance during figure-copying tasks were measured after a single oral dose of mCPP (0.5 mg/kg). mCPP-induced prolongation of the reaction times in all copying tasks, parallel to increases in cortisol and prolactin and some self-reported behavioral effects. There were no changes in the movement times or the velocities of the w