WorldWideScience

Sample records for ethers orally administration

  1. Administration of Injectable Vitamin K Orally.

    Science.gov (United States)

    Afanasjeva, Janna

    2017-10-01

    Background: Vitamin K, or phytonadione, is available in both injectable and oral formulations. Oral vitamin K is available as 5-mg tablets, but the key drawbacks for using vitamin K tablets consist of availability of only 1 dose strength and recent tripling of the product's cost over a 2-year period. An interest exists for utilization of injectable vitamin K via oral route. Method: A literature search was performed on April 26, 2017, to identify any studies describing the use of injectable vitamin K for oral administration. The search involved PubMed and Embase and utilized various combinations of keywords vitamin K, phytonadione, IV, intravenous, injectable, and oral. The results were limited to studies that discussed oral administration of injectable vitamin K. The efficacy of the injectable preparation of vitamin K administered orally was explored in 6 studies and one cost-savings project. Results: Based on the available literature, the administration of injectable vitamin K via oral route is effective and safe. Injectable vitamin K for oral administration can be prepared as an undiluted solution or as a compounded solution. These 2 formulations have different beyond-use dates depending on ingredients used. Conclusion: Information on efficacy and stability of injectable vitamin K formulations prepared for oral administration provides an additional option for health care systems when vitamin K tablets are unavailable or cost-prohibitive to use.

  2. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

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

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

  3. 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....

  4. 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.

  5. 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.

  6. In vivo efficacy of oral and intraperitoneal administration of extracts ...

    African Journals Online (AJOL)

    In vivo efficacy of oral and intraperitoneal administration of extracts of Warburgia ugandensis (Canellaceae) in experimental treatment of old world cutaneous leishmaniasis caused by Leishmania major .

  7. [Amenorrhea following the administration of oral contraceptives].

    Science.gov (United States)

    Gertrudis Diez, M A

    1984-04-01

    It is estimated that about 2.2% of women experience amenorrhea and anovulatory cycles after discontinuing use of oral contraceptives (OCs), although exact figures are lacking due to differences of definition and problems of diagnosis. Several possible mechanisms to explain the occurrence of postpill amenorrhea have been suggested, including endometrial atrophy and fibrosis, changes in the ovaries similar to those found in Stein-Levanthal syndrome, hypothalamic disorder, late menarche, irregular cycles, and periods of amenorrhea before or during OC use. Previous pregnancies, duration of pill use, and formulation utilized are apparently not related to occurrence of post-pill amenorrhea. Clinical diagnosis requires detection of ovulation by means of basal body temperature, cervical mucus changes, and vaginal smears. If amenorrhea persists after administration of a progestagen to induce bleeding, more complete examinations must be done to exclude pituitary tumor, Cushing's syndrome, thyroid problems, and possible precocious menopause or anorexia nervosa. X-rays, administration of thyroid or suprarenal hormones, gonadotropins, or estrogens, an endometrial biopsy, or laparoscopy may be necessary. Generally all test values are normal except that levels of estrogens, follicle stimulating hormone, and luteinizing hormone are usually reduced. Treatment of post-pill amenorrhea can take various forms. About 5% of cases appear to resolve spontaneouusly; efforts should therefore be made to detect ovulation through basal body temperature, cervical mucus and vaginal smears. Corticosteroids including prednisone and dexametasone may administrered, or if estrogen levels are low and the patient fails to respond to progestagens with withdrawal bleeding, clomiphene may be used. Human menopausal gonadotropin or human chorionic gonadotropin can be in patients with low estrogen levels who do not respond to clomiphene. Ergocriptine derivatives may be used in cases with associated

  8. Histological Studies Of The Effects Of Oral Administration Of ...

    African Journals Online (AJOL)

    Histological studies of the effect of oral administration of Damiana extract on the liver of mature wistar rats was carried out at the Department of Anatomy, University of Ilorin, Kwara State between December 2002 and July 2003. This study involved the oral administration of 0.52mg Damiana extract daily on various days.

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

    African Journals Online (AJOL)

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

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

    Indian Academy of Sciences (India)

    2013-07-22

    Jul 22, 2013 ... 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 ...

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

    Indian Academy of Sciences (India)

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

  12. New oral solid dosage form for furosemide oral administration.

    Science.gov (United States)

    Perioli, Luana; D'Alba, Giuseppina; Pagano, Cinzia

    2012-04-01

    Furosemide (FURO) is a drug labeled in class IV of the Biopharmaceutics Classification System (BCS) as it is both poor soluble and poor permeable. The aim of this work was to improve FURO biopharmaceutical properties by its formulation in a new solid oral dosage form. It consists in the realization of the composite MgAl-HTlc-FURO, obtained by FURO intercalation into the inorganic matrix hydrotalcite (MgAl-HTlc), and its successive formulation in tablets intended to be swallowed whole and to disintegrate rapidly in the stomach. These formulations were prepared by direct compression of a simple powder mixture constituted by MgAl-HTlc-FURO, a super disintegrant (Explotab, PolyplasdoneXL, PolyplasdoneXL-10, PolyplasdoneINF 10 or L-HPCLH-21) and a filler. The prepared formulations were submitted to disintegration time tests, and only those displaying the lowest disintegration time in gastric medium were submitted to in vitro release studies. Drug dissolution profiles from MgAl-HTlc-FURO tablets were compared with those containing crystalline FURO alone or physically mixed to MgAl-HTlc instead of MgAl-HTlc-FURO. The results revealed that tablets containing MgAl-HTlc-FURO give the best dissolution profile and that L-HPCLH-21 is able to promote the highest drug release in gastric medium, resulting in the most suitable super disintegrant in comparison with the other tested. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Prevention of Adiposity by the Oral Administration of ?-Cryptoxanthin

    OpenAIRE

    Takayanagi, Katsuhiko

    2011-01-01

    β-Cryptoxanthin (β-CRX) is a carotenoid found in human blood. It is specifically rich in Satsuma mandarin (Citrus unshiu Marc.) but very little in other fruits or vegetables. Several reports indicate the health promoting benefits of β-CRX. As we had reported visceral fat reduction on mildly obese male by the oral administration of β-CRX, a detailed mechanism has not been identified. To identify the mechanism, obese model mouse, TSOD was used in the present study. Oral administration of β...

  14. Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration.

    Science.gov (United States)

    Green, Jody L; Bucher Bartelson, Becki; Le Lait, M Claire; Roland, Carl L; Masters, Elizabeth T; Mardekian, Jack; Bailey, J Elise; Dart, Richard C

    2017-06-01

    Prescription opioid abuse and misuse is a serious and growing public health issue. While the most common form of abuse is swallowing intact tablets/capsules, some abusers manipulate, or tamper with, these medications by altering the dosage form to allow for non-oral routes of administration (e.g., injection, inhalation) in order to achieve more rapid or enhanced psychoactive effects. Because administration of opioids via non-oral routes results in greater systemic availability and more rapid central nervous system penetration, we hypothesized that death and major medical outcomes occur more frequently with non-oral routes compared to oral route alone. This retrospective cohort study analyzed data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program to investigate relative risk of prescription opioid abuse via oral and non-oral routes. While the oral route was the most commonly reported route of abuse (64.0%), non-oral routes were reported in 14.6% exposures and unknown routes in 21.4% exposures. The relative risk of an exposure resulting in death or major effect was 2.43 (95% CI 1.97, 2.99) if non-oral routes were reported compared to exposures involving oral route only. Analysis of acute health events recorded by poison centers indicates that death or major effects are twice as likely to occur with intentional abuse of prescription opioids via non-oral routes of administration than ingestion alone. Effective interventions to prevent abuse via non-oral routes of solid dosage forms of prescription opioids, such as abuse-deterrent formulations could have a significant public health impact. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    The oral administration of solution of drugs or test substances to experimental rats is often necessary in various pharmacological, toxicological and other biomedical researches. It is scientifically sound and preferable to administer test substances to experimental animals by the same route(s) by which it is taken or meant to ...

  16. Pharmacokinetics of oestriol after repeated oral administration to dogs

    NARCIS (Netherlands)

    Hoeijmakers, M.; Janszen, B.; Coert, A.; Horspool, L.

    2003-01-01

    The aim of the present study was to investigate the pharmacokinetics of oestriol in plasma in the dog after repeated oral administration of oestriol tablets, a preparation intended for the treatment of urinary incontinence in the bitch. The study was performed in six healthy, entire, adult female

  17. Impact of oral and intramuscular administration amoxicillin on the ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to evaluate the level of selection of amoxicillin-resistant Enterobacteriaceae in the digestive microbiota of piglets during oral and intramuscular administration of amoxicillin. Methodology and Results: Enumeration of Enterobacteriaceae was carried out on MacConkey agar with and ...

  18. Effect of Oral Administration of Pheretima Aspergillum (Earthworm ...

    African Journals Online (AJOL)

    Immunostaining was used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B, and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that oral administration of PA for two weeks to rats with MCAo successfully reduced cerebral infarction areas in the cortex and striatum, and also ...

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  1. Implications of oral administration of extracts of Acalypha wilkesiana ...

    African Journals Online (AJOL)

    The leaves of Acalypha wilkesiana are eaten as vegetables as part of the traditional management of hypertension in Nigeria. This study was therefore conducted to evaluate the implications of oral administration of extracts of Acalypha wilkesiana leaves, on serum electrolytes, urea and creatinine, in normal experimental ...

  2. Hepatotoxic effects of low dose oral administration of monosodium ...

    African Journals Online (AJOL)

    The present study is aimed at investigating the potentials of low concentration administration of monosodium glutamate in inducing hepatotoxic effects in male albino rats. Thus, monosodium glutamate at a dose of 5 mg/kg of body weight was administered to adult male albino rats by oral intubation. Treatment was daily for ...

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

    African Journals Online (AJOL)

    DR. AMINU

    Received: February, 2010. Accepted: May, 2010. EFFECT OF ORAL ADMINISTRATION OF AQUEOUS EXTRACT OF CASSIA. OCCIDENTALIS L. SEEDS ON SERUM ELECTROLYTES CONCENTRATION IN. RATS. *Abubakar, S.M. and Sule, M.S.. Department of Biochemistry, Bayero University, P.M.B. 3011, Kano, Nigeria ...

  4. The effects of oral administration of Croton penduliflorus seed oil ...

    African Journals Online (AJOL)

    This study investigated the effects of oral administration of Croton penduliflorus seed oil (CSPO) and Depo provera on liver and kidney function of pregnant rabbits. Graded doses of CSPO were suspended in 5% Tween 20 solution. Twenty-five pregnant Dutch-white rabbits at mid–gestation were allocated into 5 groups.

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

    African Journals Online (AJOL)

    Histological studies of the effects of oral administration of aqueous extract of Phyllanthus amarus commonly used in ethno medical practice in Africa for the management of various ailments such as kidney stones, dysentery, jaundice, diarrhoea and urogenital diseases on the kidney of adult Wistar rats were carefully studied.

  6. Effect of oral administration of Gnidia Stenophylla Gilg aqueous root ...

    African Journals Online (AJOL)

    Background: Aqueous preparations of a medicinal plant, Gnidia stenophylla Gilg (Thymelaeaceae) are commonly used to cure malaria and other ailments in Ethiopia. This study evaluated the safety of the plant extract by determining its effects on food intake and histology of gastrointestinal tract (GIT) after oral administration ...

  7. Oral administration of Gongronema latifolia leaf meal: Implications ...

    African Journals Online (AJOL)

    Jane

    2011-06-27

    Jun 27, 2011 ... characteristics of broilers fed these diets. M.Sc. Thesis, Department of Animal Science, University of Ibadan, Nigeria. Antai AB, Ofem OE, Ikpi DE, Ukafia S, Agiang A (2009). Phytochemistry and some haematological changes following oral administration of ethanolic root extract of Gongronema latifolium in ...

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

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-16

    May 16, 2008 ... The effect of ethanolic extract of leaf and root of Rauwolfia vomitoria on kidney and liver functions in rats was investigated. Rats were given daily oral administration of ethanolic extracts of either root or leaf of R. vomitoria at two different concentrations (1.0 and 2.0 g/kg body weight) for a period of 14 days.

  9. Oral 2-oleyl glyceryl ether improves glucose tolerance in mice through the GPR119 receptor

    DEFF Research Database (Denmark)

    Hassing, H A; Engelstoft, M S; Sichlau, R M

    2016-01-01

    The intestinal G protein-coupled receptor GPR119 is a novel metabolic target involving glucagon-like peptide-1 (GLP-1)-derived insulin-regulated glucose homeostasis. Endogenous and diet-derived lipids, including N-acylethanolamines and 2-monoacylglycerols (2-MAG) activate GPR119. The purpose...... of this work is to evaluate whether 2-oleoyl glycerol (2-OG) improves glucose tolerance through GPR119, using wild type (WT) and GPR 119 knock out (KO) mice. We here show that GPR119 is essential for 2-OG-mediated release of GLP-1 and CCK from GLUTag cells, since a GPR119 specific antagonist completely...... abolished the hormone release. Similarly, in isolated primary colonic crypt cultures from WT mice, GPR119 was required for 2-OG-stimulated GLP-1 release while there was no response in crypts from KO mice. In vivo, gavage with 2-oleyl glyceryl ether ((2-OG ether), a stable 2-OG analog with a potency of 5.3 µ...

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

    Science.gov (United States)

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

    2012-10-01

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

  11. Anti-cancer activity of bromelain nanoparticles by oral administration.

    Science.gov (United States)

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.

  12. Therapeutic effects on murine oral candidiasis by oral administration of cassia (Cinnamomum cassia) preparation.

    Science.gov (United States)

    Taguchi, Yuuki; Takizawa, Toshio; Ishibashi, Hiroko; Sagawa, Takehito; Arai, Ryo; Inoue, Shigeharu; Yamaguchi, Hideyo; Abe, Shigeru

    2010-01-01

    We examined the effects of spices and herbs on Candida albicans growth using in vitro assay and therapeutic activity of some selected herbal preparations against murine oral candidiasis. All tested samples: lemongrass (Cymbopogon citratus), lemon balm (Melissa officinalis), thyme (Thymus vulgaris), rosemary (Rosmarinus officinalis), roselle (Hibiscus sabdariffa), green tea (Camellia sinensis), and cassia (Cinnamomum cassia) inhibited Candida mycelial growth in vitro. The results of this assay showed that the anti-Candida activity of lemongrass, green tea, and cassia is stronger than that of the other tested herbs. Oral administration of lemongrass or green tea did not result in significant improvement in the murine oral candidiasis, while the administration of cassia improved the symptoms and reduced the number of viable Candida cells in the oral cavity. The results of in vitro Candida growth assay including GC/MS analysis suggested that cinnamaldehyde in the cassia preparation was the principal component responsible for the inhibitory activity of Candida mycelial growth. These findings suggest that oral intake of a cassia preparation is a clinical candidate for a prophylactic or therapeutic tool against oral Candida infection.

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

    Science.gov (United States)

    Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik

    2017-01-01

    Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa. We concluded that treatment with lappa, which was within the safety range, resulted in body weight decrease and blood glucose suppression. PMID:29046701

  14. Multifunctional Nanotube-Mucoadhesive Poly(methyl vinyl ether-co-maleic acid)@Hydroxypropyl Methylcellulose Acetate Succinate Composite for Site-Specific Oral Drug Delivery.

    Science.gov (United States)

    Kerdsakundee, Nattha; Li, Wei; Martins, João Pedro; Liu, Zehua; Zhang, Feng; Kemell, Marianna; Correia, Alexandra; Ding, Yaping; Airavaara, Mikko; Hirvonen, Jouni; Wiwattanapatapee, Ruedeekorn; Santos, Hélder A

    2017-10-01

    An advanced oral drug delivery system that can effectively deliver drugs with poor oral bioavailability is strongly desirable. Herein, a multifunctional nano-in-micro structured composite is developed by encapsulation of the mucoadhesive poly(methyl vinyl ether-co-maleic acid) modified halloysite nanotubes (HNTs) with the pH-responsive hydroxypropyl methylcellulose acetate succinate by the microfluidics to control the drug release, increase cell-particle interaction, and improve drug absorption. The microparticles show spherical shape, homogeneous particle size distribution (58 ± 1 µm), and pH-responsive dissolution behavior at pH > 6, and they prevent the premature release of curcumin in simulated pH conditions of the stomach and immediately release the curcumin in simulated pH conditions of the small intestine. The surface modification of HNT with mucoadhesive poly(methyl vinyl ether-co-maleic acid) significantly enhances its interactions with the intestinal Caco-2/HT29-MTX cells and the mouse small intestines, and increases the permeability of curcumin across the co-cultured Caco-2/HT29-MTX cell monolayers by about 13 times compared to the free curcumin. Therefore, the developed multifunctional nanotube-mucoadhesive poly(methyl vinyl ether-co-maleic acid)@hydroxypropyl methylcellulose acetate succinate composite is a promising oral drug delivery system for drugs with poor oral bioavailability. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis.

    Science.gov (United States)

    Machin, Daniel R; Clifton, Heather L; Richardson, Russell S; Wray, D Walter; Donato, Anthony J; Frech, Tracy M

    2017-01-01

    Systemic sclerosis (SSc) is a rare, autoimmune disease characterised by endothelial dysfunction, which is associated with peripheral vasculopathy, such as digital ulcers (DU). We sought to determine if acute oral administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase, would augment endothelial function in patients with SSc. Twelve SSc patients, of whom a majority had a history of DU, were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design. There were no differences in blood markers of oxidative stress and brachial artery blood pressure, diameter, blood velocity, shear rate, or blood flow at rest between placebo and BH4 (p>0.05). Whereas, after a 5 minute suprasystolic forearm cuff occlusion, brachial artery peak reactive hyperemia (placebo: 313±30 vs. BH4: 347±37 ml/min, pacute BH4 administration, indicating an improvement in endothelial function. To determine if the vasodilatory effects of BH4 were specific to the vascular endothelium, brachial artery blood flow and vasodilation in response to sublingual nitroglycerin were assessed, and were found to be unaffected by BH4 (p>0.05). These findings indicate that acute BH4 administration ameliorates endothelial dysfunction in patients with SSc. Given that endothelial dysfunction is known to be associated with DU in SSc patients, this study provides a proof-of-concept for the potential therapeutic benefits of BH4 in the prevention or treatment of DU in this population.

  16. Thermal antinociception following oral administration of tapentadol in conscious cats.

    Science.gov (United States)

    Doodnaught, Graeme M; Evangelista, Marina C; Steagall, Paulo V M

    2017-03-01

    To evaluate the onset, magnitude and duration of thermal antinociception after oral administration of two doses of tapentadol in cats. Prospective, randomized, blinded, experimental study. Six healthy adult cats weighing 4.4 ± 0.4 kg. Skin temperature (ST) and thermal threshold (TT) were evaluated using a wireless TT device up to 12 hours after treatment. Treatments included placebo (PBO, 50 mg dextrose anhydrase orally), buprenorphine (BUP, 0.02 mg kg(-1)) administered intramuscularly, low-dose tapentadol (LowTAP, 25 mg orally; mean 5.7 mg kg(-)(1)) and high-dose tapentadol (HighTAP, 50 mg orally; mean 11.4 mg kg(-)(1)) in a blinded crossover design with 7 day intervals. Statistical analysis was performed using anova with appropriate post hoc test (p ≤ 0.05). Salivation was observed immediately following 11 out of 12 treatments with tapentadol. The ST was significantly increased at various time points in the opioid treatments. Hyperthermia (≥ 39.5 °C) was not observed. Baseline TT was 45.4 ± 1.4 °C for all treatments. Maximum TT values were 48.8 ± 4.8 °C at 1 hour in LowTAP, 48.5 ± 3.0 °C at 2 hours in HighTAP and 50.2 ± 5.3 °C at 1 hour in BUP. TT significantly increased after LowTAP at 1 hour, after HighTAP at 1-2 hours, and after BUP at 1-2 hours compared with baseline values. TTs were significantly increased in BUP at 1-2 hours compared with PBO. Oral administration of tapentadol increased ST and TT in cats. The durations of thermal antinociception were similar between HighTAP and BUP, both of which were twice as long as that in LowTAP. Studies of different formulations may be necessary before tapentadol can be accepted into feline practice. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  17. Residue depletion of valnemulin in swine tissues after oral administration.

    Science.gov (United States)

    Huang, Qiushi; Li, Jiancheng; Xia, Lijun; Xia, Xi; Duan, Peng; Shen, Jianzhong; Ding, Shuangyang

    2010-04-01

    The depletion profile of valnemulin (VLM) was studied in healthy piglets after oral administration of a premix. Thirty pigs were given doses of 7.5 mg/kg body weight/day in the feed for 21 days. One control and five medicated piglets were randomly selected for sacrifice at 0.25, 0.5, 1, 2 and 3 days post-treatment. The residue concentrations of VLM in swine muscle, liver and kidney were detected using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The highest residue concentrations of VLM were attained in 0.25 day, and all of the samples were below the maximum residue limit (MRL) recommended by the European Medical Evaluation Agency (EMEA) at 0.5 day post-treatment. The residue concentrations of swine liver were significantly higher than those of kidney and muscle, which indicated liver to be the target tissue for VLM. The withdrawal period of VLM with oral administration was 24 hours. 2010. Published by Elsevier B.V.

  18. Pharmacokinetics of bisphenol S in humans after single oral administration.

    Science.gov (United States)

    Oh, Jiwon; Choi, Jeong Weon; Ahn, Young-Ah; Kim, Sungkyoon

    2017-12-19

    Bisphenol S (BPS) has been introduced as a substitute for bisphenol A (BPA), and widely used in the manufacture of polycarbonate plastics, epoxy resins and thermal papers. Despite its adverse health outcomes and widespread exposure, pharmacokinetic data of BPS are not available for either animals or humans. The objective of the study is to describe pharmacokinetic characteristics of BPS in human body after a single oral administration with a compartmental pharmacokinetic model. Seven healthy young adults were orally exposed to 8.75μg/bw of d4-BPS, and serum and urine samples were collected for 48h. The concentrations of total and unconjugated d4-BPS in samples were measured using HPLC-MS/MS. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment model was constructed and validated. As a result of non-compartmental analysis, total d4-BPS was rapidly absorbed within 1h (0.7±0.3h) after oral administration, and excreted in urine with terminal half-life of BPS for 48h was 92±17% (67-104%) for men and 70±36% (59-77%) for women. The two-compartment model well described pharmacokinetic properties of BPS, and its parameter estimates were consistent with those from non-compartmental analysis. This study provides information on absorption, distribution, metabolism and elimination of BPS in human body, and the pharmacokinetic model can be utilized for estimating exposure dose of BPS, contributing to more realistic exposure assessment. Copyright © 2017. Published by Elsevier Ltd.

  19. Treatment of melasma with oral administration of tranexamic acid.

    Science.gov (United States)

    Wu, Sufan; Shi, Hangyan; Wu, Hua; Yan, Sheng; Guo, Jincai; Sun, Yi; Pan, Lei

    2012-08-01

    Melasma is a common pigmentary disorder among Asian women. The available therapies such as bleaching agents, chemical peeling, laser, and intense pulsed light are not satisfactory or safe. In the search to find a new treatment therapy for melasma, oral administration of tranexamic acid (TA) was studied clinically in Chinese patients. The study enrolled 74 patients. Tranexamic acid tablets were prescribed at a dosage of 250 mg twice daily for a therapeutic period of 6 months. All the patients were followed up for more than 6 months after the treatment. The effects of treatment were evaluated by two physicians independently and by the patient based on improvement of pigmentation and reduction in melasma size. These were graded into four levels: excellent, good, fair, and poor. After 6 months of treatment, the effects were graded as follows: excellent (10.8%, 8/74), good (54%, 40/74), fair (31.1%, 23/74), and poor (4.1%, 3/74). Side effects of TA such as gastrointestinal discomfort (5.4%) and hypomenorrhea (8.1%) were observed, but no severe complications were found. The recurrence of melasma was observed in seven cases (9.5%). Oral administration of TA is an effective and safe therapy for the treatment of melasma. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

  20. Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms

    Directory of Open Access Journals (Sweden)

    Kazuo Azuma

    2015-09-01

    Full Text Available The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs and surface-deacetylated (SDA CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old were fed a normal diet and administered tap water with 0.1% (v/v CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP, adenosine diphosphate (ADP, and serotonin (5-hydroxytryptamine, 5-HT. Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.

  1. Oral administration of GZ-793A, a VMAT2 inhibitor, decreases methamphetamine self-administration in rats.

    Science.gov (United States)

    Wilmouth, Carrie E; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P; Bardo, Michael T

    2013-11-01

    Despite the high prevalence of use of methamphetamine (METH), there is no FDA-approved pharmacological treatment available currently for METH addiction. The vesicular monoamine transporter (VMAT2) has been proposed as a novel target to treat METH abuse. GZ-793A, a lobelane analog and selective VMAT2 inhibitor, has been shown previously to decrease METH self-administration specifically when administered via the subcutaneous route in rats. Since oral administration is the preferred clinical route, the present experiments determined if oral administration of GZ-793A would decrease specifically METH self-administration. Experiments 1 and 2 assessed the dose-effect functions of oral administration of GZ-793A (30-240 mg/kg) on intravenous METH self-administration and food-maintained responding, respectively. Experiments 3 and 4 assessed the time-course (20-180 min pretreatment) of oral administration of GZ-793A on METH self-administration and food-maintained responding, respectively. Oral administration of GZ-793A dose-dependently decreased METH self-administration, with the highest dose (240 mg/kg) producing an 85% decrease compared to control baseline. The decrease in METH self-administration produced by GZ-793A (120 mg/kg) lasted at least 180 min. In contrast, GZ-793A failed to alter food-maintained responding at any of the doses or pretreatment intervals tested. The oral effectiveness and the specificity of GZ-793A to decrease methamphetamine self-administration support the feasibility of developing VMAT2 inhibitors as treatments for METH abuse. © 2013.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Oral alcohol administration disturbs tear film and ocular surface.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Jung Ha; Nam, Woo Ho; Yi, Kayoung; Choi, Dong Gyu; Hyon, Joon Young; Wee, Won Ryang; Shin, Young Joo

    2012-05-01

    To investigate whether ethanol administration disturbs the tear film and ocular surface. Case-control study. Twenty healthy male subjects were recruited. Ethanol was administered to 10 subjects and another 10 subjects served as controls. Twenty healthy male subjects with no ocular disease were recruited. Ethanol (0.75 g/kg) was administered orally at 8 pm for 2 hours to 10 subjects. The tear film and ocular surface were evaluated at 6 pm before drinking, at midnight, and immediately (6 am) and 2 hours (8 am) after waking the next morning. Tear osmolarity, ethanol concentration in tears and serum, Schirmer's test results, tear film break-up time (TBUT), corneal punctuate erosion, and corneal sensitivity were measured. Ethanol was detected in tears and serum at midnight, but it was not detected the next morning. The mean tear osmolarity level increased in the alcohol group at midnight compared with that in the control group (Ptears. Ethanol in tears induced tear hyperosmolarity and shortened TBUT and triggered the development of ocular surface diseases. Similar changes could exacerbate signs and symptoms in patients with ocular surface disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  5. [What are the reasons for patient preference? A comparison between oral and subcutaneous administration].

    Science.gov (United States)

    Quante, M; Thate-Waschke, I; Schofer, M

    2012-09-01

    Today there are different subcutaneous and three oral applicable medications for prevention of venous thromboembolism after knee and hip replacement. It is a general opinion that patients will prefer oral administration. However, until today there has been no study that analysed patient preferences and motives for deciding on the kind of administration. These data would be of interest since the consideration of patient preferences could improve adherence. The present study analysed patient preferences regarding oral or subcutaneous administration of medication after elective hip or knee replacement surgery. The results will have implications for clinical practice and for decision-making concerning the kind of administration. This prospective, multi-centric, observational study was conducted in six emergency hospitals and six rehabilitation hospitals. 178 current hip and knee replacement patients undergoing thromboprophylaxis and at least one further oral medication were interviewed. Subjective assessment data of patients were collected on study-specific questionnaires (epidemiological data, amount and background of general oral medication, details on subcutaneous thromboprophylaxis, preference of administration, causes for preference). 71.91 % of the interviewed patients preferred the daily intake of a tablet, whereas only 14.61 % favoured the daily subcutaneous injection. Main causes for the preference of oral administration were easier (86.6 % of nominations) and less complex (73.1 % of nominations) handling. 70.9 % reported that one more oral application would be unproblematic. Painlessness of oral administration was relevant for 65.7 %. Causes for preferring subcutaneous administration were "safety" (55.3 % of nominations) and an assumption of a generally better effectivity of subcutaneous (47.4 % of nominations) administration. Subjective discomfort induced by subcutaneus administration increased with the time interval since surgery. Less than 5 % of patients

  6. Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration : relation to efficacy in kidney allografting

    NARCIS (Netherlands)

    Schuurman, HJ; Slingerland, W; Mennninger, K; Ossevoort, M; Hengy, JC; Dorobek, B; Vouderscher, J; Ringers, J; Odeh, M; Jonker, Margreet

    In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values (+/- SD) of C-max, 24-h area-under-the curve (AUC) and 24-h trough

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

    OpenAIRE

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

    2017-01-01

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care...

  8. Therapeutic effects of orally administrated antioxidant drugs on acute noise-induced hearing loss.

    Science.gov (United States)

    Choi, C-H; Du, X; Floyd, R A; Kopke, R D

    2014-03-01

    The objective of this study was to investigate the dose-dependent therapeutic effect of the orally administrated antioxidant drugs [4-hydroxy alpha-phenyl-tert-butylnitrone (4-OHPBN) and N-acetyl-L-cysteine (NAC)] on acute noise-induced hearing loss because oral administration is the most commonly used method of drug administration due to its convenience, safety, and economical efficiency. Thirty chinchilla were exposed to a 105 dB octave band noise centered at 4 kHz for 6 h and randomly assigned to a control group (saline only) and three experimental groups [4-OHPBN (10 mg/kg) plus NAC (20 mg/kg), 4-OHPBN (20 mg/kg) plus NAC (50 mg/kg), and 4-OHPBN (50 mg/kg) plus NAC (100 mg/kg)]. The drugs were orally administrated beginning 4 h after noise exposure and then administered twice daily for the next 2 days. Permanent auditory brainstem response threshold shifts, distortion product otoacoustic emission threshold shifts, and the percentage of missing outer hair cell were determined. The oral administration significantly reduced permanent hearing threshold shift, distortion product otoacoustic emission threshold shift, and the percentage of missing outer hair cell in a dose-dependent manner. This result demonstrates that orally administered drugs can treat acute noise-induced hearing loss in a dose-dependent manner. This suggests that oral administration was effective in treating acute noise-induced hearing loss as in intraperitoneal administration.

  9. Coronary Spastic Angina Induced after Oral Desmopressin (DDAVP) Administration.

    Science.gov (United States)

    Adachi, Yusuke; Sakakura, Kenichi; Akashi, Naoyuki; Wada, Hiroshi; Momomura, Shin-Ichi; Fujita, Hideo

    A 60-year-old man was prescribed oral desmopressin (1-deamino-8-D-arginine vasopressin acetate trihydrate; DDAVP) for nocturnal polyuria. One week after starting to take desmopressin, he frequently felt chest pain while resting. Coronary angiography revealed no organic stenosis; however, an acetylcholine provocation test showed severe coronary spasm with ST elevation. He was diagnosed with coronary spastic angina, and we stopped the oral desmopressin and added diltiazem. While DDAVP should dilate the coronary vessels in healthy subjects, it may provoke coronary vasospasm in patients with endothelial dysfunction. We should be careful to avoid triggering coronary spasm when administering DDAVP to patients that may have potential endothelial dysfunction.

  10. Gastrostomy tube placement for long-term oral drug administration in non-human primates.

    Science.gov (United States)

    Kim, Jong-Min; Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jung-Sik; Yoon, Il-Hee; Jeong, Won-Young; Lee, Ga-Eul; Kim, Min-Sun; Kim, Ju-Eun; Park, Chung-Gyu

    2017-03-01

    Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long-term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary. The aim of this study was to compare the efficacy of between oral drug administration in restraint and administration using gastrostomy tube and to report complications and solutions to overcome the problems related to gastrostomy tube for long-term oral drug dosing in rhesus monkeys. Fifteen of 4- to 5-year-old male and female healthy rhesus monkeys weighing 5.0-6.8 kg were used as recipients for porcine pancreatic islet transplantation. Oral drug administration in restraint was used for four monkeys, and gastrostomy tube was placed to other 11 monkeys (8-French Feeding tube, n=6; Tri-Funnel Replacement Gastrostomy tube, n=5). Oral immunosuppressive drugs such as sirolimus and tacrolimus were administered through the tube. The efficacy and the extent of ease for administration and related complications were compared between two groups. The complication of gastrostomy included a transient inflammation in the skin and peritonitis caused by a leakage around implantation site (one case), which could be overcome by changing suture method and tube type to interlocking box suture and Tri-Funnel Replacement Gastrostomy tube, respectively. Despite these complications, oral drug administration using gastrostomy tube allowed us to perform accurate dosage of drug administration and to reduce the stress that both the monkey and the researcher may experience. Taken together, this study showed that

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Gastrointestinal Absorption of Hesperidin and Hesperetin after Oral Administration of Immature Citrus Unshiu Extract to Rats

    OpenAIRE

    藤田, 忠; 川瀬, 篤史; 西島, 七恵; 増田, めぐみ; 松田, 秀秋; 岩城, 正宏; Tadashi, Fujita; Atsushi, Kawase; Nanae, Nishijima; Megumi, Masuda; Hideaki, Matsuda; Masahiro, Iwaki; 近畿大学薬学部; 近畿大学薬学部; 近畿大学薬学部

    2008-01-01

    Hesperidin and hesperetin having an antiallergic effect are contained abundantly in immature fruit of Citrus unshiu. However, the gastrointestinal absorption of hesperidin and hesperetin as an aglycone of hesperidin after oral administration of Citrus unshiu extract (CU-ext) has not been clarified. We developed a simultaneous HPLC analysis for hesperidin and hesperetin in plasma and investigated the pharmacokinetics of hesperidin and hesperetin after oral administration of CU-ext compared wit...

  14. The pharmacokinetics of diclofenac sodium following intravenous and oral administration.

    Science.gov (United States)

    Willis, J V; Kendall, M J; Flinn, R M; Thornhill, D P; Welling, P G

    1979-01-01

    The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 microgram . ml-1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.

  15. Early effects of oral administration of esomeprazole and omeprazole on the intragastric pH.

    Science.gov (United States)

    Iida, Hiroshi; Inamori, Masahiko; Okuno, Kotone; Sekino, Yusuke; Sakai, Eiji; Okubo, Hidenori; Higurashi, Takuma; Endo, Hiroki; Hosono, Kunihiro; Yoneda, Masato; Koide, Tomoko; Takahashi, Hirokazu; Goto, Ayumu; Kubota, Kensuke; Saito, Satoru; Maeda, Shin; Nakajima, Atsushi; Gotoh, Eiji

    2015-01-01

    The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral dose of a proton pump inhibitor, esomeprazole 20 mg and omeprazole 20 mg. A total of 14 Helicobacter pylori-negative male subjects participated in this study. Intragastric pH was monitored continuously for 6 hours after a single oral dose of omeprazole 20 mg and a single oral dose of esomeprazole 20 mg. Each administration was separated by a 7-day washout period. During the 6-hour study period, the average pH after administration of esomeprazole was higher than that after the administration of omeprazole. Also during the 6-hour study period, each of pH > 2, 3, 3.5, 4, and 5 was maintained for a longer duration after administration of esomeprazole 20 mg than after administration of omeprazole 20 mg (median: 75.4% vs. 53.8%, p = 0.0138; 52.1% vs. 33.4%, p = 0.0188; 45.8% vs. 28.2%, p = 0.0262; 42.5% vs. 20.7%, p = 0.0414; 35.8% vs. 11.6%, p = 0.0262; respectively). In Helicobacter pylori-negative healthy male subjects, single oral administration of esomeprazole 20 mg increased the intragastric pH more rapidly than single oral administration of omeprazole 20 mg.

  16. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration.

    Science.gov (United States)

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-07

    Fluralaner is a novel systemic insecticide and acaricide. The purpose of these studies was to investigate the pharmacokinetic properties of fluralaner in Beagle dogs following single oral or intravenous (i.v.) administration. Following the oral administration of 12.5, 25 or 50 mg fluralaner/kg body weight (BW), formulated as chewable tablets or i.v. administration of 12.5 mg fluralaner/kg BW, formulated as i.v. solution to 24 Beagles, plasma samples were collected until 112 days after treatment. Plasma concentrations of fluralaner were measured using HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods. After oral administration, maximum plasma concentrations (C(max)) were reached within 1 day on average. Fluralaner was quantifiable in plasma for up to 112 days after single oral and i.v. treatment. The apparent half-life of fluralaner was 12-15 days and the mean residence time was 15-20 days. The apparent volume of distribution of fluralaner was 3.1 L/kg, and clearance was 0.14 L/kg/day. Fluralaner is readily absorbed after single-dose oral administration, and has a long elimination half-life, long mean residence time, relatively high apparent volume of distribution, and low clearance. These pharmacokinetic characteristics help to explain the prolonged activity of fluralaner against fleas and ticks on dogs after a single oral dose.

  17. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration

    OpenAIRE

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer KA; Nuernberger, Martin C

    2014-01-01

    Background Fluralaner is a novel systemic insecticide and acaricide. The purpose of these studies was to investigate the pharmacokinetic properties of fluralaner in Beagle dogs following single oral or intravenous (i.v.) administration. Methods Following the oral administration of 12.5, 25 or 50 mg fluralaner/kg body weight (BW), formulated as chewable tablets or i.v. administration of 12.5 mg fluralaner/kg BW, formulated as i.v. solution to 24 Beagles, plasma samples were collected until 112...

  18. 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.

  19. Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

    Science.gov (United States)

    Kato, Karin; Nagao, Miki; Yamamoto, Masaki; Matsumura, Yasufumi; Takakura, Shunji; Fukuda, Kazuhiko; Ichiyama, Satoshi

    2016-01-01

    Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole. Copyright © 2015. Published by Elsevier Ltd.

  20. 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...... of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief....

  1. Labor Induction with Orally Administrated Misoprostol: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Tove Wallstrom

    2017-01-01

    Full Text Available Introduction. One great challenge in obstetric care is labor inductions. Misoprostol has advantages in being cheap and stable at room temperature and available in resource-poor settings. Material and Methods. Retrospective cohort study of 4002 singleton pregnancies with a gestational age ≥34 w at Sodersjukhuset, Stockholm, during 2009-2010 and 2012-2013. Previously used methods of labor induction were compared with misoprostol given as a solution to drink, every second hour. Main outcome is as follows: Cesarean Section (CS rate, acid-base status in cord blood, Apgar score 1500 ml (PPH. Results. The proportion of CS decreased from 26% to 17% when orally given solution of misoprostol was introduced at the clinic (p<0.001. No significant difference in the frequency of low Apgar score (p=0.3, low aPh in cord blood (p=0.1, or PPH (p=0.4 between the different methods of induction was studied. After adjustment for different risk factor for CS the only method of induction which was associated with CS was dinoproston⁎⁎ (Propess® (aor = 2.9 (1.6–5.2. Conclusion. Induction of labor with misoprostol, given as an oral solution to drink every second hour, gives a low rate of CS, without affecting maternal or fetal outcome.

  2. 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.

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

    African Journals Online (AJOL)

    Objectives: The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. Methods: In the present study, ameliorating effect of 200 mg/kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and ...

  4. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    Science.gov (United States)

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    Silvia Carloni

    2017-12-01

    Full Text Available Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24–72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg−1 melatonin, or 3 boluses of 1 or 5 mg·kg−1 of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC from 10.48 to 118.17 µg·mL−1·h−1. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h.

  6. Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous, oral and intravenous administration.

    Science.gov (United States)

    Karademir, U; Erdogan, H; Boyacioglu, M; Kum, C; Sekkin, S; Bilgen, M

    2016-05-01

    To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5 mg/kg bodyweight. Five healthy Saanen goats, aged 12-14 months and weighing 35-40 kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5 mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group. Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (pmeloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.

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

    Science.gov (United States)

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

    2013-06-01

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

  8. Sick Sinus Syndrome After a Single Oral Administration of Garenoxacin

    Directory of Open Access Journals (Sweden)

    Chiyo Sugiyama, MD

    2010-01-01

    Full Text Available This report presents the case of a 60-year-old female who demonstrated sick sinus syndrome after a single administration of Garenoxacin (GRNX. She was administered GRNX for an upper respiratory infection and 10 minutes thereafter, she suddenly felt palpitation and numbness of both arms. She was transferred to the hospital 2 hours after taking GRNX. An electrocardiogram showed bradycardia with junctional escape beats and the longest sinus arrest was 4 seconds. She was treated with a temporary pacemaker and 21 hours after the administration of GRNX her sinus node function was observed to have completely improved. GRNX-induced sick sinus syndrome was suspected because her clinical course was compatible with the concentration of GRNX and her other cardiological assessments, including an electrophysiologic study (EPS which were conducted on the 9th day of the admission, were normal. GRNX has less effect on the QT interval than other quinolone agents. However, physicians should be aware of the risk of sick sinus syndrome because GRNX is frequently prescribed in outpatient clinics.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... and colon from pigs killed at 2, 3 and 6 h after dosing. Intramuscular administration resulted in significantly higher concentrations in plasma, intestinal tissue and lymph nodes at 2 h but not at 3 or 6 h compared with p.o. administration. The absorption and distribution phase was longer after oral....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

  10. Oral fluid and plasma cannabinoid ratios after around-the-clock controlled oral Δ(9)-tetrahydrocannabinol administration.

    Science.gov (United States)

    Milman, Garry; Schwope, David M; Schwilke, Eugene W; Darwin, William D; Kelly, Deanna L; Goodwin, Robert S; Gorelick, David A; Huestis, Marilyn A

    2011-11-01

    Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ(9)-tetrahydrocannabinol (THC, dronabinol) doses (40-120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = -0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high interindividual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations.

  11. Oral Fluid and Plasma Cannabinoid Ratios after Around-the-Clock Controlled Oral Δ9-Tetrahydrocannabinol Administration

    Science.gov (United States)

    Milman, Garry; Schwope, David M.; Schwilke, Eugene W.; Darwin, William D.; Kelly, Deanna L.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. METHODS Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ9-tetrahydrocannabinol (THC, dronabinol) doses (40–120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. RESULTS Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = −0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. CONCLUSIONS OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high inter-individual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations. PMID:21875944

  12. Disposition of eslicarbazepine acetate in the mouse after oral administration.

    Science.gov (United States)

    Alves, Gilberto; Figueiredo, Isabel; Castel-Branco, Margarida; Lourenço, Nulita; Falcão, Amílcar; Caramona, Margarida; Soares-da-Silva, Patrício

    2008-10-01

    Eslicarbazepine acetate is a promising antiepileptic drug structurally related to carbamazepine and oxcarbazepine, which is in the final phase of clinical development. The metabolism of eslicarbazepine acetate is clearly species dependent and, in this case, among small laboratory animals, the mouse seems to be the most relevant species to humans. Hence, the aim of this study was to investigate the plasma, brain and liver disposition of eslicarbazepine acetate in mice to better understand its disposition in humans. Adult male CD-1 mice were treated orally with a single dose of eslicarbazepine acetate 350 mg/kg. Blood samples, brain and liver tissues were taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 10, 16 and 24 h post-dose. Plasma and tissue levels of eslicarbazepine acetate and its metabolites (S-licarbazepine, R-licarbazepine and oxcarbazepine) were assessed by using high-performance liquid chromatography-ultraviolet detection. Both eslicarbazepine acetate and R-licarbazepine concentrations were below the limit of quantification of the assay in all matrices. Eslicarbazepine acetate was rapidly and extensively metabolized to S-licarbazepine (major metabolite), which was oxidized to oxcarbazepine to a small extent. The brain/plasma ratios suggest that the brain exposure to S-licarbazepine and oxcarbazepine was approximately 30% of their total systemic exposure. However, S-licarbazepine crossed the blood-brain barrier (BBB) less efficiently than oxcarbazepine. On the other hand, the liver/plasma ratios support the notion that S-licarbazepine undergoes hepatic accumulation, whereas oxcarbazepine appears to leave this compartment twice as fast as S-licarbazepine. Thus, the diffusion through the BBB is favourable to oxcarbazepine and the liver acts like a deposit of the pharmacologically active metabolite of eslicarbazepine acetate (S-licarbazepine).

  13. 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......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  14. Bioequivalence assessment of ambroxol orally-disintegrating tablet after a single oral-dose administration to healthy volunteers.

    Science.gov (United States)

    Ni, Yaojun; Hou, Lili; Chen, Liang; Fan, Jiang

    2016-05-01

    In this study, a modified LC-MS/MS method was used to determine plasma ambroxol concentration and thereby examine the bioequivalence of two ambroxol medications among healthy Chinese male volunteers. The study used a single-dose, randomized, open-label design principle and calculated pharmacokinetic parameters for the comparison of the two formulations. Administration of a single oral dose of either the test drug or reference drug was found to be safe in healthy subjects. No severe, serious, or life-threatening clinical or drug-related side effects were reported during the study. The majority of clinical laboratory test results were within the normal range or not clinically significant. The pharmacokinetic parameters for ambroxol oral tablets and ambroxol orally disintegrating tablets were comparable. For the comparison of the two formulations, the 90% confidence intervals for the log-transformed pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf) fell within the bioequivalenceambroxol oral tablets were bioequivalent to ambroxol orally-disintegrating tablets in healthy human adult male volunteers, under fasting conditions.

  15. Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats.

    Science.gov (United States)

    Vishkautsan, Polina; Papich, Mark G; Thompson, George R; Sykes, Jane E

    2016-09-01

    OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range. ANIMALS 6 healthy cats. PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15. RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation. CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects.

  16. Recent Advances of Poly(ether-ether) and Poly(ether-ester) Block Copolymers in Biomedical Applications.

    Science.gov (United States)

    He, Zhi-Yao; Shi, Kun; Wei, Yu-Quan; Qian, Zhi-Yong

    2016-01-01

    Poly(ether-ether) and poly(ether-ester) block copolymers have been widely applied in biomedical fields over two decades due to their good safety and biocompatibility. Poly(ethylene glycol), poly(ethylene glycol)-poly(propylene glycol) and poly(lactic-co-glycolic acid) have been approved as excipients by Food and Drug Administration. Because of the broad perspective in biomedical fields, many novel poly(etherether) and poly(ether-ester) block copolymers have been developed for drug delivery, gene therapy and tissue engineering in recent years. This review focuses on active targeting theranostic systems, gene delivery systems and tissue engineering based on poly(ether-ether) and poly(ether-ester) block copolymers. We perform a structured search of bibliographic databases for peer-reviewed scientific reports using a focused review question and inclusion/exclusion criteria. The literatures related to the topics of this review are cataloged according to the developed copolymers or their applications such as active targeting theranostic systems, gene delivery systems and tissue engineering. Some important advances and new trends are summarized in this review. Some commercial poly(ether-ether) copolymers have been used as excipients for drug research and development. Amphiphilic and biodegradable poly(ether-ester) diblock copolymers are capable of formulating biomedical nanoparticulate theranostic systems, and targeting moiety-functionalized poly(ether-ester) diblock copolymers will be further developed and applied in biomedical nanotechnology fields in the near future. Meanwhile, triblock or multiblock poly(ether-ether) and poly(ether-ester) copolymers with environmentsensitive properties are suitable for gene delivery and tissue engineering. Poly(ether-ether) and poly(ether-ester) copolymers are being extensively applied in active targeting theranostic systems, gene delivery systems and tissue engineering. Biodegradable, environment-sensitive and targeting moiety

  17. 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.

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

    Science.gov (United States)

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

    2015-12-03

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

  19. Pharmacokinetics of the triazole antifungal agent genaconazole in healthy men after oral and intravenous administration.

    Science.gov (United States)

    Mojaverian, P; Radwanski, E; Affrime, M B; Cayen, M N; Lin, C C

    1994-01-01

    The pharmacokinetics of genaconazole, a potent new difluorophenyl-triazole antifungal agent, was studied in 12 healthy male volunteers following a single oral or intravenous administration of the drug. In a randomized two-way crossover design, each volunteer received either two 50-mg genaconazole tablets orally or a parenteral preparation containing 100 mg of genaconazole given as a 30-min intravenous infusion. Both dosage regimens were well tolerated. Blood and urine samples were collected up to 10 days after drug administration. Concentrations of genaconazole in plasma and urine were determined by a specific high-performance liquid chromatography assay with a limit of quantitation of 0.1 microgram/ml. Pharmacokinetic evaluation following oral and intravenous doses indicated that mean values for the area under the concentration-time curve from 0 h to infinity (137 and 136 micrograms.h/ml), half-life (50 and 49 h), volume of distribution (52 and 52 liters), and clearance (12 and 12 ml/min) were independent of the route of drug administration. The oral and intravenous administrations of genaconazole yielded virtually superimposable plasma concentration-time curves, resulting in an absolute bioavailability of 100%. Amounts of unchanged genaconazole found in urine samples from 0 to 240 h after oral and intravenous doses were comparable, and urinary excretion accounted for 76 and 78% of the administered dose, respectively. Renal clearances for the two routes of administration were also similar, and renal clearance accounted for over 80% of the total body clearance. The 100% absolute bioavailability of genaconazole regardless of the route of administration provides greater dosing flexibility in various clinical settings than currently exists. PMID:7695258

  20. 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.

  1. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration.

    Science.gov (United States)

    Walther, Feli M; Paul, Allan J; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-06

    Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration.

  2. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  4. Effect of oral fructose administration on alchohol-induced increase in ...

    African Journals Online (AJOL)

    Effect of oral fructose administration on alchohol-induced increase in plasma urate. ... The stimulation of alcohol oxidative metabolism by fructose may not be accompanied by a threatening increase in serum urate, the aetiologic risk factor of gout, renal calculi and hypertension. Albeit, similar study designed for humans is ...

  5. Evaluation of oral administration of cortisol as a model for prenatal stress in pregnant sows

    NARCIS (Netherlands)

    Kranendonk, G.; Hopster, H.; Eerdenburg, van F.; Reenen, van C.G.; Wolthuis-Fillerup, M.; Groot, de J.; Korte, S.M.; Taverne, M.

    2005-01-01

    Objective - To design a treatment that increases plasma corticosteroid concentrations to mimic prenatal stress in pregnant sows. Animals - 24 pregnant sows. Procedure - Sows were assigned to 1 of 4 treatment groups; treatment consisted of twice-daily oral administration of a placebo or 20, 60, or

  6. Oral administration of nimodipine accelerates functional recovery following peripheral nerve damage in the rat

    NARCIS (Netherlands)

    Gispen, W.H.; Zee, C.E.E.M. van der; Schuurman, T.; Traber, J.

    1987-01-01

    Oral administration of the Ca2+-entry blocker nimodipine accelerates in a dose-dependent manner the recovery of sensorimotor function following a crush lesion of the rat sciatic nerve. The beneficial effect of nimodipine was apparent in both a foot shock withdrawal test and in a test analyzing the

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

    OpenAIRE

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

    2010-01-01

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

  8. Errors of oral medication administration in a patient with enteral feeding tube.

    Science.gov (United States)

    Emami, Shahram; Hamishehkar, Hadi; Mahmoodpoor, Ata; Mashayekhi, Simin; Asgharian, Parina

    2012-07-01

    Enteral feeding tube is employed for feeding of critically ill patients who are unable to eat. In the cases of oral medication administration to enterally fed patients, some potential errors could happen. We report a 53-year-old man who was admitted to intensive care unit (ICU) of a teaching hospital due to the post-CPR hypoxemic encephalopathy. The patient was intubated and underwent mechanical ventilation. A nasogastric (NG) tube was used as the enteral route for nutrition and administration of oral medications. Oral medications were crushed then dissolved in tap water and were given to the patient through NG tube. In present article we report several medication errors occurred during enterally drug administration, including errors in dosage form selection, methods of oral medication administration and drug interactions and incompatibility with nutrition formula. These errors could reduce the effects of drugs and lead to unsuccessful treatment of patient and also could increase the risk of potential adverse drug reactions. Potential leading causes of these errors include lack of drug knowledge among physicians, inadequate training of nurses and lack of pharmacists participation in medical settings.

  9. Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available of surface coating with various concentrations of polymeric surfactants (PEG and Pluronics F127) on the in vitro protein binding as well as the tissue biodistribution, post oral administration, of PLGA nanoparticles. The in vitro protein binding varied...

  10. Use of hydrophobins in formulation of water insoluble drugs for oral administration

    NARCIS (Netherlands)

    Haas Jimoh Akanbi, Marijke; Post, Eduard; Meter-Arkema, Anita; Rink, Rick; Robillard, George T; Wang, Xiaoqin; Wösten, Han A B; Scholtmeijer, Karin

    2010-01-01

    The poor water solubility of many drugs requires a specific formulation to achieve a sufficient bioavailability after oral administration. Suspensions of small drug particles can be used to improve the bioavailability. We here show that the fungal hydrophobin SC3 can be used to make suspensions of

  11. Oral Administration of Vitamin C and Vitamin E amelioratesLead ...

    African Journals Online (AJOL)

    Background: Lead toxicity is a public health concern. Lead is one of the dispensable and non-biodegradable heavy metals and is toxic even at low concentrations. Objective: This study was to investigate the effect of oral administration of Vitamin C and Vitamin E on lead-induced hepatotoxicity and oxidative stress in the ...

  12. 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.

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

    Science.gov (United States)

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

    2010-04-01

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

  14. Effects of Oral Administration of Aloe Vera Plus on the Heart and ...

    African Journals Online (AJOL)

    Alasia Datonye

    Effects of Oral Administration of Aloe Vera Plus on the Heart and Kidney: A Subacute Toxicity Study in Rat Models. O.C. Koroye* I.M. Siminialayi ** E.N. Etebu *. *Federal Medical Center, Yenagoa, Bayelsa State and **Department of Pharmacology, College of Health Sciences, University of Port Harcourt. ABSTRACT.

  15. 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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration.

    Science.gov (United States)

    Sundlof, S F; Whitlock, T W

    1992-09-01

    Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one-compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats.

  18. 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.

  19. Toxicity of Bromkal 70-5DE, a technical mixture of polybrominated diphenyl ethers, following 28 d of oral exposure in rats and impact of analysed impurities.

    Science.gov (United States)

    Oberg, Mattias; Westerholm, Emma; Fattore, Elena; Stern, Natalia; Hanberg, Annika; Haglund, Peter; Wiberg, Karin; Bergendorff, Anders; Håkansson, Helen

    2010-06-01

    The subacute toxicity of a commercial polybrominated diphenyl ether (PBDE) preparation, Bromkal 70-5DE, was investigated. In addition to a vehicle control, the mixture was given orally to male and female Sprague-Dawley rats for 28 d at three dose levels; 2.5, 25 and 250 mg kg(-1) b.w.d(-1). The observed effects include increased hepatic EROD activity (from 2.5 mg kg(-1)d(-1)); increased liver weight (males), increased PROD activity and depletion of hepatic retinoids (from 25 mg kg(-1)d(-1)); and increased liver weight (females), marked histological changes in the liver and lungs, as well as increased serum parameters such as total protein, cholesterol and albumin (from 250 mg kg(-1)d(-1)). Chemical analysis of the PBDE mixture with gas chromatography/mass spectrometry (GS/MS) showed impurities of polybrominated dibenzofurans and to a lesser extent dibenzodioxins, in total levels of about 7.0 microg g(-1) of Bromkal technical mixture. The animals were thereby exposed to an estimated dose of dioxin-like equivalents corresponding to 1.3-131 ng TEQ kg(-1) b.w.d(-1). It cannot be ruled out that this level of impurities can explain the hepatic EROD induction and hepatic retinoid depletion, which are considered typical markers of toxicity mediated via the aryl hydrocarbon receptor (AhR). Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-09-01

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

  1. Quality improvement of oral medication administration in patients with enteral feeding tubes.

    Science.gov (United States)

    van den Bemt, P M L A; Cusell, M B I; Overbeeke, P W; Trommelen, M; van Dooren, D; Ophorst, W R; Egberts, A C G

    2006-02-01

    The correct administration of oral drugs to patients on enteral tube feeding presents a special challenge. As patients are usually unable to swallow oral drugs and many drugs should not be crushed, ways have to be found to administer them through the feeding tube. Measures to improve the quality of oral drug administration in patients with enteral feeding tubes may consist of introducing guidelines, training nurses, or giving patient-tailored advice by the pharmacy. An integrated program comprising all these measures is likely to result in the greatest improvements. A study was undertaken in two Dutch hospitals to investigate the effect of such an integrated program. The integrated program in hospital I resulted in a decrease in the number of tube obstructions (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.047 to 1.05). There was a significant decrease in the number of administration errors per nurse in hospital II (OR 0.003, 95% CI 0.0005 to 0.02). This multidisciplinary program comprising several interventions to promote the correct administration of drugs through an enteral feeding tube results in substantial improvements. As errors concerning administration of drugs to patients with enteral feeding tubes may lead to adverse drug events and loss of effect, these improvements are likely to contribute to a decrease in patient morbidity.

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

    Science.gov (United States)

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

    2011-08-01

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

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

    Science.gov (United States)

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

    2012-08-01

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

  4. 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

  5. Effect of oral methyl-t-butyl ether (MTBE) on the male mouse reproductive tract and oxidative stress in liver

    Science.gov (United States)

    de Peyster, Ann; Rodriguez, Yvonne; Shuto, Rika; Goldberg, Beck; Gonzales, Frank; Pu, Xinzhu; Klaunig, James E.

    2015-01-01

    MTBE is found in water supplies used for drinking and other purposes. These experiments follow up on earlier reports of reproductive tract alterations in male mice exposed orally to MTBE and explored oxidative stress as a mode of action. CD-1 mice were gavaged with 400–2000 mg/kg MTBE on days 1, 3, and 5, injected ip with hCG (2.5 IU/g) on day 6, and necropsied on day 7. No effect was seen in testis histology or testosterone levels. Using a similar dosing protocol, others had initially reported disruption of seminiferous tubules in MTBE–gavaged mice, although later conclusions published were consistent with our findings. Another group had also reported testicular and other reproductive system abnormalities in male BALB/c mice exposed for 28 days to 80–8000 ug/ml MTBE in drinking water. We gave these MTBE concentrations to adult mice for 28 days and juvenile mice for 51 days through PND 77. Evidence of oxidative stress was examined in liver homogenates from the juvenile study using MDA, TEAC and 8OH2hG as endpoints. MTBE exposures at the levels examined indicated no significant changes in the male mouse reproductive tract and no signs of hepatic oxidative stress. This appears to be the first oral MTBE exposure of juvenile animals, and also the first to examine potential for MTBE to cause oxidative stress in vivo using a typical route of human exposure. PMID:18824092

  6. 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.

  7. Oral anticoagulant dosing, administration, and storage: a cross-sectional survey of Canadian health care providers.

    Science.gov (United States)

    Piran, Siavash; Schulman, Sam; Panju, Mohamed; Pai, Menaka

    2017-11-23

    Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) offer patients accurate information and counselling around DOACs, to optimize safe and effective use. To assess knowledge around oral anticoagulant indication, dosing, storage, and administration, an electronic survey was distributed to HCPs across Canada from June to August 2017, with 18 questions on the practical use of oral anticoagulants. A total of 191 responses were received: 100 from nurse practitioners, 42 from pharmacists, 27 from Hematologists, 5 from Thrombosis specialists, 4 from internists, 9 from residents and fellows, and 2 each from family physicians and registered nurses. Only 51 (26.7%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs. Only 101 (52.9%) correctly identified that DOACs are not approved for treatment of heparin-induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. 112 (58.6%) felt comfortable or very comfortable prescribing oral anticoagulants. Half of the respondents knew that dabigatran should not be crushed, however only 85 (44.5%) knew that it should not be exposed to moisture. 94 (49%) knew that higher dose rivaroxaban should be taken with food. The results of our study demonstrate that there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants. Future research should focus on educational interventions to improve HCPs' knowledge around indications, dosing, storage, and administration, with the goal of enhancing patient safety.

  8. Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation.

    Science.gov (United States)

    Torrado, J J; Illum, L; Cadorniga, R; Davis, S S

    1990-01-01

    Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed.

  9. Pharmacokinetics of meloxicam after intramuscular and oral administration of a single dose to American flamingos (Phoenicopertus ruber).

    Science.gov (United States)

    Boonstra, Jennifer L; Cox, Sherry K; Martin-Jimenez, Tomas

    2017-03-01

    OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber). ANIMALS 14 adult flamingos. PROCEDURES Flamingos were allocated to 2 groups. Each group received a dose of meloxicam (1 mg/kg) by the IM or oral route. After a 4-week washout period, groups received meloxicam via the other route of administration. Plasma meloxicam concentrations were measured with high-performance liquid chromatography. Data for each bird were analyzed. Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA. Pooled concentration-time profiles for each route of administration were analyzed to examine the influence of body weight on pharmacokinetics. RESULTS Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration. This was approximately 15% of the mean maximum plasma concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean time to maximum plasma concentration was 1.33 ± 1.32 hours after oral administration and 0.28 ± 0.17 hours after IM administration. Mean half-life of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent and rate of meloxicam absorption were less after oral administration than after IM administration. Intramuscular administration resulted in a short period during which mean plasma concentrations met or exceeded reported efficacious analgesic concentrations in other species, whereas oral administration did not. These results suggested that higher doses may be required for oral administration.

  10. Dynamic observation of 18F-FDG uptake after oral administration in a healthy subject.

    Science.gov (United States)

    Zhang, Kaixiu; Wang, Xuemei; Hao, Linjun; Zhao, Zhenfeng; Han, Chunlei

    2013-06-01

    PET with (18)F-FDG is a widely used imaging modality in cancer patients. Traditionally, (18)F-FDG is administrated intravenously. However, patients with difficult venous access are not rare in clinical practice. The purpose of the current study was to investigate the dynamic process of (18)F-FDG distribution after oral administration in order to determine the optimal imaging acquisition time in human subjects. On the basis of tissue time-activity curves, we determined the time that was required to reach 90% of the maximal uptake in target organs. In a 50-y-old healthy subject with oral (18)F-FDG administration, we found that (18)F-FDG uptake maximized at 60 min for most organs except for the gray matter of the brain, which continued to accumulate (18)F-FDG after 60 min. Time to 90% was 22 min for liver, 36 min for kidneys, 48 min for myocardium, 50 min for bladder, 56 min for sigmoid colon, and greater than 61 min for gray matter of the brain. We suggest that PET images be acquired at around 60 min after oral (18)F-FDG administration for most organs. For the brain, a longer interval is required before acquisition.

  11. Enhanced learning of normal adult rodents by repeated oral administration of soybean transphosphatidylated phosphatidylserine.

    Science.gov (United States)

    Kataoka-Kato, Akito; Ukai, Makoto; Sakai, Masashi; Kudo, Satoshi; Kameyama, Tsutomu

    2005-07-01

    Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) is already known to improve the learning ability of aged or drug-induced amnesic rodents. In this study, its effect on normal adult rodents was evaluated using several learning tasks. Firstly, three behavioral tests (open-field, Y-maze, and active avoidance test) were consecutively carried out after the daily oral administration of SB-tPS (50 mg/kg per day, for 34 days). Repeated oral administration of SB-tPS did not affect either exploratory behavior in the open-field test or spontaneous alternation behavior in the Y-maze test, while mice pretreated with SB-tPS showed significant enhancement of conditioned avoidance response. Secondly, the brightness discrimination test was used to evaluate the effect of SB-tPS on learning ability. The daily oral administration of SB-tPS (50 mg/kg per day, for 27 days) to normal rats significantly increased the correct response ratio in the brightness discrimination test. Finally, to elucidate the necessity of SB-tPS pretreatment, another active avoidance test was carried out, and no enhancement of conditioned avoidance response was observed in non-pretreated mice. These results suggest that repeated administration of SB-tPS could enhance the learning ability of normal adult rodents as those of aged ones.

  12. Oral administration of stavudine induces hyperalgesia without affecting activity in rats.

    Science.gov (United States)

    Weber, Juliane; Mitchell, Duncan; Kamerman, Peter R

    2007-12-05

    We have investigated whether long-term oral administration of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine affects nociception in Sprague-Dawley rats, and whether any changes of nociception are accompanied by deterioration in activity and appetite. Stavudine (50 mg kg(-1)) was administered to rats orally once daily for six weeks in gelatine cubes. Mechanical hyperalgesia of the tail was assessed using a bar algometer, and thermal hyperalgesia by tail immersion in 49 degrees C water. Withdrawal latencies were compared to those of rats receiving placebo gelatine cubes. Withdrawal latencies to the noxious thermal challenge were not affected by stavudine, but those to the mechanical challenge were significantly decreased in rats receiving stavudine, compared to rats receiving placebo, from week three to week six of drug administration (Prats was assessed by recording daily voluntary wheel running distance and maximum running speed, food intake and body mass. Daily stavudine administration did not adversely affect voluntary running activity, appetite or growth. We have shown that long-term daily oral administration of the NRTI stavudine results in mechanical hyperalgesia in rats within three weeks without affecting appetite, growth and physical activity.

  13. Oral administration of Lactobacillus brevis KB290 to mice alleviates clinical symptoms following influenza virus infection.

    Science.gov (United States)

    Waki, N; Yajima, N; Suganuma, H; Buddle, B M; Luo, D; Heiser, A; Zheng, T

    2014-01-01

    Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle 'Suguki', has been reported to have immunomodulatory effects. We investigated whether oral administration of KB290 has protective effects against influenza virus (IFV) infection in mice. After 14 days of administration of lyophilized KB290 suspended in phosphate-buffered saline by oral gavage, BALB/c mice were intranasally infected with 2 × MLD50 (50% mouse lethal dose) of IFV A/PR/8/34 (H1N1). Prophylactically administered KB290 significantly alleviated the loss of body weight and the deterioration in observational physical conditions induced by the infection. In addition, 7 days after infection, the levels of IFV-specific immunoglobulin (Ig)A in bronchoalveolar lavage fluid were significantly increased in mice fed KB290 compared with controls. Moreover, there was a significant elevation of serum interferon (IFN)-α in KB290 group mice, even at three and 7 days after infection, despite the administration of KB290 being stopped before IFV infection. Our results demonstrated that oral administration of KB290 before infection could alleviate IFV-induced clinical symptoms. Alleviation of clinical symptoms by KB290 consumption may have been induced by long-lasting enhancement of IFN-α production and the augmentation of IFV-specific IgA production. This study demonstrated that oral administration of Lactobacillus brevis KB290 (KB290), a probiotic strain derived from a Japanese traditional pickle, could protect against influenza virus (IFV) infection in mice. Our results demonstrated that continual intake of KB290 for 14 days prior to IFV infection alleviated clinical symptoms such as loss of body weight and deterioration in observational physical conditions induced by the infection. The beneficial effects of KB290 consumption may have been elicited by the long-lasting enhancement of interferon-α production and the augmentation of IFV-specific immunoglobulin A production. © 2013 The

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

    DEFF Research Database (Denmark)

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5 mg, 10 mg, 25 mg and 50mg bupivacaine, respectively, was administered...... as single dose to 10 healthy invididuals and lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to 5 HNC patients. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the HNC patients, respectively......-compartment distribution model with absorption transit compartments. All observed plasma concentrations were well below bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was 2-fold higher in HNC patients with oral mucositis grade 1-2, and 3...

  15. Pharmacokinetic, pharmacodynamic and biodistribution following oral administration of nanocarriers containing peptide and protein drugs.

    Science.gov (United States)

    Griffin, Brendan T; Guo, Jianfeng; Presas, Elena; Donovan, Maria D; Alonso, María J; O'Driscoll, Caitriona M

    2016-11-15

    The influence of nanoparticle (NP) formulations on the pharmacokinetic, pharmacodynamic and biodistribution profiles of peptide- and protein-like drugs following oral administration is critically reviewed. The possible mechanisms of absorption enhancement and the effects of the physicochemical properties of the NP are examined. The potential advantages and challenges of physiologically-based pharmacokinetic (PBPK) modelling to help predict efficacy in man are discussed. The importance of developing and expanding the regulatory framework to help translate the technology into the clinic and accelerate the availability of oral nanoparticulate formulations is emphasized. In conclusion, opportunities for future work to improve the state of the art of oral nanomedicines are identified. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Detection of urine and blood clenbuterol following short-term oral administration in the horse.

    Science.gov (United States)

    Chuang, M S; Huang, H H; Dixon, K M; Chen, K S; Mao, C L; Chen, C L

    2010-03-01

    The pharmacokinetics of clenbuterol in equine urine and blood was investigated. Urine and blood samples were collected following 3-day multiple oral administrations. The samples were examined using enzyme-linked immunosorbent assay and further confirmed by solid phase extraction and capillary electrophoresis. Urinary clenbuterol was detectable until day 14 after the last dose. The urinary excretion of clenbuterol was characterized by a biphasic pattern. The half-lives of the bi-exponential elimination (t(1/2alpha) and t(1/2beta)) for urinary clenbuterol were about 12.1 and 48 hours. After a single oral administration (4 microg/kg) of clenbuterol, the half-life of serum clenbuterol was approximately 11.4 hours.

  17. 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.

  18. AmbiOnp: solid lipid nanoparticles of amphotericin B for oral administration.

    Science.gov (United States)

    Patel, Pratikkumar A; Patravale, Vandana B

    2011-10-01

    Amphotericin B is the most effective gold standard drug against various fungal infections, especially in second line treatment of leishmaniasis. However, its usefulness is limited due to severe nephrotoxicity, which may lead to kidney failure. Due to its poor oral bioavailability, it is often administered parenterally to patients suffering from systemic fungal infection or visceral leishmaniasis (kala azar). In this investigation, solid lipid nanoparticles were formulated for oral administration of Amphotericin B. For this purpose, novel microemulsion based nanoprecipitation technique was employed. The influence of process variables such as sonication and dialysis time was studied. The optimized formulation was characterized for parameters such as particle size, polydispersity index, zeta potential, drug content and entrapment efficiency. The pH stability of the developed Amphotericin B solid lipid nanoparticles (AmbiOnp) at pH 1.2, 4, 6.8 values demonstrated enhanced protection of entrapped Amphotericin B. Further, single dose acute toxicity study established the safety of AmbiOnp for oral administration. In vivo pharmacokinetic studies revealed increase in % relative bioavailability of AmbiOnp in comparison to the plain drug. Additionally, the t1/2 of encapsulated Amphotericin B was significantly greater than that of plain drug, indicating the controlled release of Amphotericin B from AmbiOnp. Overall, the developed formulation; AmbiOnp was found to be successful in oral delivery of Amphotericin B.

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

    Science.gov (United States)

    Yuan, Yue; Chen, Xiao-yan; Li, San-ming; Wei, Xiu-yan; Yao, Hui-min; Zhong, Da-fang

    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 AUC0–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. PMID:19543299

  20. Errors of oral medication administration in a patient with enteral feeding tube

    OpenAIRE

    Emami, Shahram; Hamishehkar, Hadi; Mahmoodpoor, Ata; Mashayekhi, Simin; Asgharian, Parina

    2012-01-01

    Enteral feeding tube is employed for feeding of critically ill patients who are unable to eat. In the cases of oral medication administration to enterally fed patients, some potential errors could happen. We report a 53-year-old man who was admitted to intensive care unit (ICU) of a teaching hospital due to the post-CPR hypoxemic encephalopathy. The patient was intubated and underwent mechanical ventilation. A nasogastric (NG) tube was used as the enteral route for nutrition and administratio...

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

    African Journals Online (AJOL)

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

  2. Effect of Oral Administration of Butyrivibrio fibrisolvens MDT-1 on Experimental Enterocolitis in Mice▿

    OpenAIRE

    Ohkawara, Sou; Furuya, Hideki; Nagashima, Kousuke; Asanuma, Narito; Hino, Tsuneo

    2006-01-01

    Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (109 CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mit...

  3. 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. Copyright © 2015. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2011-09-01

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

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

    Science.gov (United States)

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

    2016-04-30

    Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500  mg/m 2 /day 2500  mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10  ppb 40±10  ppb (2±0.5  pM 2±0.5  pM ) before capecitabine administration to 27.7±11.8  ppm 27.7±11.8  ppm (14.6±6.5  nM 14.6±6.5  nM ) after application, p<0.001 p<0.001 . The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.

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

    Science.gov (United States)

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

    2016-04-01

    Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, p<0.001. The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.

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

    Science.gov (United States)

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

    2015-12-01

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

  8. Prevention of adiposity by the oral administration of β-cryptoxanthin

    Directory of Open Access Journals (Sweden)

    Katsuhiko eTakayanagi

    2011-11-01

    Full Text Available β-Cryptoxanthin (β-CRX is a carotenoid found in human blood. It is specifically rich in Satsuma mandarin (Citrus unshiu Marc. but very little in other fruits or vegetables. Several reports indicate the health promoting benefits of β-CRX. As we had reported visceral fat reduction on mildly obese male by the oral administration of β-CRX, a detailed mechanism has not been identified. To identify the mechanism, obese model mouse, TSOD was used in the present study. Oral administration of β-CRX repressed body weight, abdominal adipose tissue weight and serum lipid concentrations on TSOD mice. The outstanding observation is the significant repression of adipocyte hypertrophy. DNA micro array analysis strongly indicates that the oral administration of β-CRX represses the inflammatory cytokine secretion and improves the lipid metabolism and the energy consumption. It also suggests these effects are partly mediated by PPAR-α, not only lipid metabolism and adipocyte differentiation control but possibly internal circadian clock modulation.

  9. Prevention of Adiposity by the Oral Administration of β-Cryptoxanthin.

    Science.gov (United States)

    Takayanagi, Katsuhiko

    2011-01-01

    β-Cryptoxanthin (β-CRX) is a carotenoid found in human blood. It is specifically rich in Satsuma mandarin (Citrus unshiu Marc.) but very little in other fruits or vegetables. Several reports indicate the health promoting benefits of β-CRX. As we had reported visceral fat reduction on mildly obese male by the oral administration of β-CRX, a detailed mechanism has not been identified. To identify the mechanism, obese model mouse, TSOD was used in the present study. Oral administration of β-CRX repressed body weight, abdominal adipose tissue weight, and serum lipid concentrations on TSOD mice. The outstanding observation is the significant repression of adipocyte hypertrophy. DNA microarray analysis strongly indicates that the oral administration of β-CRX represses the inflammatory cytokine secretion and improves the lipid metabolism and the energy consumption. It also suggests these effects are partly mediated by PPAR-α, not only lipid metabolism and adipocyte differentiation control but possibly internal circadian clock modulation.

  10. 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.

  11. 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

  12. Lipid Nanoparticles as Potential Gene Therapeutic Delivery Systems for Oral Administration.

    Science.gov (United States)

    Dorraj, Golnar; Carreras, Juan Jose; Nunez, Hugo; Abushammala, Issam; Melero, Ana

    2017-01-01

    Gene therapy has experimented an increasing attention in the last decades, due to its enormous potential applications in the medical field. It can be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides) to treat or prevent a disease state, generally a geneticbased one. Other applications, like treating viral, bacterial or parasite infections or development of vaccines are gaining also interest. Efficient gene therapy is mainly dependent on the ability of the highly labile genetic material to reach the therapeutic target. For this purpose, different delivery systems have been designed and extensively investigated. Nanoparticles offer a broad range of possibilities in design, being prepared using biocompatible and biodegradable excipients, being therefore generally considered as safe. Oral delivery of the genetic material is also a great challenge, due to the complexity of this specific biological barrier. Special attention to all the intrinsic hazards for gene delivery due to the barrier must be taken into account during the particle design process. Particle design will also allow targeting to specific sites of the gastrointestinal tract. Solid lipid nanoparticles have been extensively studied in the oral drug delivery field, and also in gene delivery through other administration routes, but still not explored in oral gene delivery. In this manuscript, design considerations and particle-cell interaction mechanisms will be extensively reviewed, focusing on the oral route to encourage the scientific community to explore these valuable carriers for oral gene delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. 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.

  14. Pharmacokinetics of valnemulin after intravenous, intramuscular, and oral administration in layer chickens.

    Science.gov (United States)

    Sun, F; Fan, R; Wang, J; Xiong, L; Shen, J; Zhang, S; Cao, X

    2017-08-01

    The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS). The concentration-time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half-life (T1/2λz), total body clearance (Cl), and area under the plasma concentration-time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (Cmax , 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple-peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2-4 h, respectively, while the tertiary peak appeared during 5-15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  18. Pharmacokinetics of the novel atypical opioid tapentadol following oral and intravenous administration in dogs.

    Science.gov (United States)

    Giorgi, Mario; Meizler, Alon; Mills, Paul C

    2012-12-01

    Tapentadol (TAP) is a novel opioid pain reliever drug with a dual mechanism of action (mu opioid receptor agonist and noradrenaline reuptake inhibitor). It is used as an analgesic in humans, but could be of interest for veterinary species if it has a suitable pharmacokinetic profile. Six dogs were randomly assigned to two treatment groups, using an open, single-dose, two-treatment, two-period, and randomised cross-over design. Each subject received TAP at 50 and 200mg by intravenous (IV) and oral route, respectively, with a 1-week wash-out period between administrations. Blood was collected at regular intervals and the plasma concentration of TAP in each sample was measured using a validated HPLC-FL method. After IV administration, concentrations of TAP were detectable in plasma for up to 6h with a half-life in the range 38-68 min. After oral administration, drug absorption was rapid (T(max), time required to reach the maximum concentration of 47.5 min), but its bioavailability was low (4.4%). Some dose-related adverse effects, including salivation and sedation, were observed, particularly following IV administration. In summary, this study showed that TAP may be useful as an analgesic in the dog, but further studies, including in dogs requiring analgesia, are required to confirm efficacy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. [Efficacy of contrast chromoendoscopy of the colon after oral administration of indigo carmine dye].

    Science.gov (United States)

    Araujo, Sergio Eduardo Alonso; Costa, Adriana Furtado; Caravatto, Pedro Paulo de Paris; Dumarco, Rodrigo Blanco; Genzini, Tércio; de Miranda, Marcelo Perosa

    2002-01-01

    Indigo carmine dye is usually spread directly over the colon in many chromoscopic techniques aiming better visualization of a lesion already detected by conventional colonoscopy. Examination of the colon already stained by oral administration of indigo carmine dye may increase detection of small lesions resulting in higher sensibility of the colonoscopy in diagnosing diminutive lesions. Analyze the results regarding the quality of chromoscopic technique and the indigo carmine dye distribution over the colon after oral administration. Fifty patients undergoing colonoscopy were evaluated. A capsule containing 100 mg of indigo carmine dye was offered to these patients 30 min before oral mannitol prep routinely used. The indigo carmine dye contrast effect was graded as bad, regular or good according to preestablished criteria in three segments of the colon: right and left colon and the rectum. In the right colon, good indigo carmine dye contrast effect was observed in only 9 (18.8%) patients, while it was considered regular and bad in 32 (66.6%) and in 7 (14.6%) patients, respectively. A good indigo carmine dye contrast effect was never observed in this series for the left colon or in the rectum. As a matter of fact, no indigo carmine dye was observed in the left colon in 80.9% and in the rectum in 92% of patients in this series. Although it may be simple and desirable, oral administration of indigo carmine dye seems ineffective for enhancing detection of diminutive lesions by chromoscopy as result of poor colonic distribution of indigo carmine dye mainly at distal colonic sites.

  20. Final report on the safety assessment of PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate.

    Science.gov (United States)

    Robinson, Valerie; Bergfeld, Wilma F; Belsito, Donald V; Klaassen, Curtis D; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2009-01-01

    PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate are used in cosmetics as fragrance ingredients and/or solvents at concentrations of 0.4% to 2%. Propylene glycol ethers are rapidly absorbed and distributed throughout the body when introduced by inhalation or oral exposure, but the inhalation toxicity of PPG-2 methyl ether vapor, for example, is low. Aerosols, such as found with hair sprays, produce particle sizes that are not respirable. Because these ingredients are highly water-soluble, they are likely to be absorbed through the human skin only at slow rates, resulting in low blood concentrations and rapid removal by the kidney. These ingredients are not genotoxic and are not reproductive or developmental toxicants. Overall the data are sufficient to conclude that PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate are safe as used in cosmetics.

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

    Directory of Open Access Journals (Sweden)

    Federica Di Cesare

    2017-05-01

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

  2. Ethyleneglycol ethers (ethyleneglycol monomethyl ether, ethyleneglycol monomethyl ether acetate, diethyleneglycol monomethyl ether, diethyleneglycol monoethyl ether and diethyleneglycol monobutyl ether).

    NARCIS (Netherlands)

    Maclaine Pont, M.A.

    1996-01-01

    The committee recommends the following exposure limits as concentrations in air averaged over 8 hours (8 h TWA): - ethyleneglycol monomethyl ether: 1 mg/m3 (0.3 ppm) - ethyleneglycol monomethyl ether acetate: 1.5 mg/3 (0.3 ppm) - diethyleneglycol monomethyl ether: 45 mg/m3 (9 ppm) - diethyleneglycol

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

    Science.gov (United States)

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

    2015-04-01

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

  4. Oral administration of insulin in solid form to nondiabetic and diabetic dogs.

    Science.gov (United States)

    Ziv, E; Kidron, M; Raz, I; Krausz, M; Blatt, Y; Rotman, A; Bar-On, H

    1994-06-01

    It was previously demonstrated that a biologically active insulin could cross the mucosal membrane in the gut by using surface active substances. In this report we describe studies in which insulin administered orally, in a solid formulation, was effectively absorbed in the canine model. The insulin was mixed with cholate and soybean trypsin inhibitor. It was delivered orally, as enterocoated microtablets, to nondiabetic and diabetic (pancreatectomized) dogs in a fasting state. The time interval between the administration of the drug and the beginning of a decrease in the plasma glucose levels was 60-140 min. This decrease reached a minimum level of 20-40 % of the initial values and lasted for more than 90 min following administration of the drug. In this model a pronounced increment in plasma insulin levels was shown prior to the drop of plasma glucose concentrations. It is concluded that with this novel oral insulin formulation a beneficial biological effect can be achieved in the treatment of diabetes.

  5. Fate of ethion in goats after intravenous, oral and dermal administration.

    Science.gov (United States)

    Mosha, R D; Gyrd-Hansen, N; Nielsen, P

    1990-09-01

    Toxicokinetic parameters and cumulative excretion were studied in goats after intravenous, oral and dermal administration of unlabelled and 14C-ethion. Plasma concentration-time data was subjected to non-compartmental analysis. IV injection studies showed an effective half-life (t1/2) of 2 hr, a total body clearance (ClT) of 3.21.kg-1.hr-1 and a volume of distribution (Vd(ss) of 9.4 1.kg-1. Plasma levels of 14C-ethion (ethion + metabolites) were much higher and more persistent than those of unchanged ethion. Cumulative excretion of 14C-ethion was 78% of the dose with 66% in urine, 8% in faeces and 4% in milk. Oral administration resulted in low plasma levels of unchanged ethion, an absorption half-life (t1/2 abs) of 10 hr and a bioavailability of less than 5%. Cumulative excretion was 80% of the dose with 64% in urine, 14% in faeces and 1.7% in milk. Dermal application showed a t1/2 abs of 85 hr and a bioavailability of 20%. Only 0.05% of the dose was excreted unchanged in milk. It is concluded that (1) orally administered ethion is extensively metabolized in the GIT, (2) dermal application results in prolonged and limited absorption and (3) absorbed ethion is rapidly eliminated through metabolism.

  6. Fate of ethion in goats after intravenous, oral and dermal administration

    Energy Technology Data Exchange (ETDEWEB)

    Mosha, R.D.; Gyrd-Hansen, N.; Nielsen, P. (Department of Pharmacology and Toxicology, Royal Veterinary and Agricultural University, Frederiksberg C (Denmark))

    1990-01-01

    Toxicokinetic parameters and cumulative excretion were studied in goats after intravenous, oral and dermal administration of unlabelled and {sup 14}C-ethion. Plasma concentration-time data was subjected to non-compartmental analysis. IV injection studies showed an effective half-life (t{sub 1/2}) of 2 hr, a total body clearance (Cl{sub T}) of 3.2 lxkg{sup -1}xhr{sup -1} and a volume of distribution (Vd{sub (ss)}) of 9.4 lxkg{sup -1}. Plasma levels of {sup 14}C-ethion (ethion+metabolites) were much higher and more persistent than those of unchanged ethion. Cumulative excretion of {sup 14}C-ethion was 78% of the dose with 66% in urine, 8% in faeces and 4% in milk. Oral administration resulted in low plasma levels of unchanged ethion, an absorption half-life (t{sub 1/2abs}) of 10 hr and a bioavailability of less than 5%. Cumulative excretion was 80% of the dose with 64% in urine, 14% in faeces and 1.7% in milk. Dermal application showed a t{sub 1/2abs} of 85 hr and a bioavailability of 20%. Only 0.05% of the dose was excreted unchanged in milk. It is concluded that (1) orally administered ethion is extensively metabolized in the GIT, (2) dermal application results in prolonged and limited absorption and (3) absorbed ethion is rapidly eliminated through metabolism. (author).

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

    Science.gov (United States)

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

    2016-03-01

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

  8. 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.

  9. Administration of Non-Torsadogenic human Ether-à-go-go-Related Gene Inhibitors Is Associated with Better Survival for High hERG-Expressing Glioblastoma Patients.

    Science.gov (United States)

    Pointer, Kelli B; Clark, Paul A; Eliceiri, Kevin W; Salamat, M Shahriar; Robertson, Gail A; Kuo, John S

    2017-01-01

    Glioblastoma is the most malignant primary brain tumor, with a median survival of less than 2 years. More effective therapeutic approaches are needed to improve clinical outcomes. Glioblastoma patient-derived cells (GPDC) were isolated from patient glioblastomas and implanted in mice to form xenografts. IHC was performed for human Ether-à-go-go-Related Gene (hERG) expression and tumor proliferation. Sphere-forming assays with the hERG blocker E-4031 were performed on a high and low hERG-expressing lines. A glioblastoma tissue microarray (TMA; 115 patients) was used to correlate hERG expression with patient survival. Clinical data were analyzed to determine whether patient survival was affected by incidental administration of hERG inhibitory drugs and the correlative effect of patient glioblastoma hERG expression levels. hERG expression was upregulated in glioblastoma xenografts with higher proliferative indices. High hERG-expressing GPDCs showed a reduction in sphere formation when treated with hERG inhibitors compared with low hERG-expressing GPDCs. Glioblastoma TMA analysis showed worse survival for glioblastoma patients with high hERG expression versus low expression-43.5 weeks versus 60.9 weeks, respectively (P = 0.022). Furthermore, patients who received at least one hERG blocker had a better survival rate compared with patients who did not (P = 0.0015). Subgroup analysis showed that glioblastoma patients with high hERG expression who received hERG blockers had improved survival (P = 0.0458). There was no difference in survival for low hERG-expressing glioblastoma patients who received hERG blockers (P = 0.4136). Our findings suggest that hERG is a potential glioblastoma survival marker, and that already approved drugs with non-torsadogenic hERG inhibitory activity may potentially be repurposed as adjuvant glioblastoma therapy in high hERG-expressing glioblastoma patients. Clin Cancer Res; 23(1); 73-80. ©2016 AACRSee related commentary by Arcangeli and

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

    OpenAIRE

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

    2015-01-01

    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 concentr...

  11. 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...

  12. Safety of 8-weeks oral administration ofArctium lappaL.

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

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

    1990-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Eva María Guerra-Alia

    2017-11-01

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

  15. Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration.

    Science.gov (United States)

    Pairis-Garcia, Monique D; Karriker, Locke A; Johnson, Anna K; Kukanich, Butch; Wulf, Larry; Sander, Suzanne; Millman, Suzanne T; Stalder, Kenneth J; Coetzee, Johann F

    2013-08-13

    The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121-168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749-6004 ng/ml) and 946 ng/ml (range: 554-1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

  16. Enhanced bioavailability of L-carnitine after painless intradermal delivery vs. oral administration in rats.

    Science.gov (United States)

    Zhang, Suohui; Qin, Guangjiong; Wu, Yan; Gao, Yunhua; Qiu, Yuqin; Li, Fang; Xu, Bai

    2011-01-01

    In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system. In vitro study was designed to assess the effects of various skins, donor concentration and hydrogels from different carbomer derivatives on the release of LC in a Franz-type diffusion cell. The LC gel patches with carbomer 980 P were prepared and successfully applied to pharmacokinetic study of SD rats with and without FMA. Intravenous injection and oral administration were performed to support pharmacokinetic calculations and comparison of bioavailability. Enhanced delivery of LC using FMA was achieved in skin of different species in vitro studies. The 750 mg LC gel patches were applied to rats over 6 h, and approximately 27% of loaded dose was transported into rat. A 2.8-fold enhancement of absolute bioavailability for LC with FMA intradermal delivery system was observed compared with oral LC administration in vivo study. Both in vitro and in vivo studies demonstrated that the FMA intradermal delivery system can enhance the delivery and bioavailability of LC.

  17. Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes.

    Science.gov (United States)

    Loftsson, Thorsteinn; Moya-Ortega, Maria D; Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2016-05-01

    The objective of the present study was to shed some light on pharmacokinetics of cyclodextrins (CDs) and drugs after oral and parenteral administration of inclusion complexes. The complex binding constant in water can predict pharmacokinetics after parenteral administration, but it has to be considered in the context of the physiological environment, where plasma proteins compete with CDs for drug binding. Neither drug/CD nor drug/protein complexes can extravasate, but differently from proteins, CDs are readily cleared through glomerular filtration. In such intricate interrelationships, for complexes with low-to-mid binding constant, binding of drug to plasma proteins will mainly dictate the pharmacokinetics. Oppositely, for drugs showing large CD complex binding constant and low protein binding, significant decrease in distribution volume and enhanced excretion of unmetabolized drug are observed; thus, relevant changes in bioavailability can be predicted. In the case of oral administration, volume for dilution/dissolution of the complexes is relatively low and hence excess CD can hamper drug absorption from the gastrointestinal (GI) tract. CDs are well-established multipurpose excipients for overcoming organoleptic and biopharmaceutical deficiencies of a variety of drugs. Balances between free and complexed drug in the GI tract and between drug-CD binding and drug-protein binding in plasma seem to play a relevant role in drug pharmacokinetics. © 2015 Royal Pharmaceutical Society.

  18. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    Science.gov (United States)

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

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

    Science.gov (United States)

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

    2015-09-01

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

  20. Radiation protection and mitigation potential of phenylbutyrate: delivered via oral administration.

    Science.gov (United States)

    Miller, Alexandra C; Rivas, Rafael; McMahon, Robert; Miller, Karvelisse; Tesoro, Leonard; Villa, Vilmar; Yanushkevich, Daminik; Lison, Paul

    2017-09-01

    Phenylbutyrate (PB), a histone deacetylase inhibitor (HDACi) has demonstrated radiation protection in both in vitro and in vivo models. Studies previously demonstrated that PB and other HDAC inhibitors could inhibit radiation lethality in vivo by subcutaneous (s.c) injection. The objective of this study was to test the ability of oral PB treatment to protect against or to mitigate acute gamma radiation-induced lethality in vivo. Human osteoblasts cells were used to evaluate radiation survival when PB was delivered pre- or post-radiation. A 30-day radiation lethality study was used to assess the radioprotective (pre-radiation) and radiomitigative (post-radiation) capability of PB. Possible mechanisms evaluated were antioxidant activity effects, HDAC inhibition, DNA damage, and hematological recovery. Treatment of HOS cells with PB 50 μM either before or after radiation increased radiation resistance as assessed by clonogenic survival. Western blot studies showed that PB treatment acetylated histones in vivo and ameliorated the radiation-induced reduction in acetylated histone-4 (H4). Pre-radiation oral administration of PB (10 mg/kg) provided radioprotection against gamma radiation (7-11.5 Gy) with a dose reduction factor of 1.25 (p = 0.001). PB oral administration post-radiation provided moderate radiation mitigation against gamma radiation (7-11.5 Gy) and demonstrated a dose reduction factor of 1.18 (p = 0.05). PB pre-radiation and post-radiation treatment was associated with significant elevations in neutrophils and platelets and attenuation of DNA damage. These results indicate that oral PB has potential as a radiation protector and a radiation mitigator and that potential mechanisms of action include attenuation of DNA damage, antioxidant activity, and bone marrow protection.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Königsson, K; Törneke, K; Engeland, IV; Odensvik, K; Kindahl, H

    2003-01-01

    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. PMID:15074628

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if ...

  5. Safety of fluralaner chewable tablets (Bravecto), a novel systemic antiparasitic drug, in dogs after oral administration.

    Science.gov (United States)

    Walther, Feli M; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-07

    Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls.During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg.

  6. The effect of fluorination of zinc oxide nanoparticles on evaluation of their biodistribution after oral administration

    Science.gov (United States)

    Lee, Chang-Moon; Jeong, Hwan-Jeong; Kim, Dong Wook; Sohn, Myung-Hee; Lim, Seok Tae

    2012-05-01

    Monitoring of the behavior of metal nanoparticles in the body following exposure is very important for investigation of the physiological fates and safety of these nanoparticles. In this study, we investigated the behavior and accumulation of nano-scaled ZnO (20 nm) and submicro-scaled ZnO (100 nm) particles in organic tissues after oral administration using PET imaging. Both types of ZnO nanoparticle (20 or 100 nm) were labeled with the radionuclide 18F in high yield via ‘click reaction’. 18F labeling on the ZnO nanoparticles was maintained stably in simulated gastric fluid (pH 1.2) for 7 h. PET images indicated that 18F and 18F-ethoxy azide showed radioactivity in the bone and bladder 3 h after oral administration, whereas radioactivity for 18F-labeled ZnO nanoparticles was seen only in the gastrointestinal (GI) tract. At 5 h post-administration, biodistribution studies demonstrate that 18F accumulated in the bone (10.19 ± 1.1%ID g-1) and 18F-ethoxy azide showed radioactivity in the bone (7.55 ± 0.6%ID g-1), liver, and brain (0.94 ± 0.3%ID g-1). Unlike 18F and 18F-ethoxy azide, 18F-labeled ZnO nanoparticles showed radioactivity in the lung, liver and kidney including the GI tract. Submicro-scaled 18F-labeled ZnO nanoparticles (100 nm) showed stronger radioactivity in the liver and kidney compared to nano-scaled 18F-labeled ZnO nanoparticles (20 nm). In conclusion, PET imaging has the potential to monitor and evaluate the behavior of ZnO nanoparticles absorbed in organic tissues following oral exposures.

  7. [Development of semisolid dosage form of clonazepam for oral cavity administration].

    Science.gov (United States)

    Sakata, Osamu; Onishi, Hiraku; Machida, Yoshiharu

    2010-01-01

    A semisolid dosage form of clonazepam (CZP), administered to the oral cavity between the lower gum and bottom lip with small volume of saline, was developed to obtain the stable dosage which can replace the injection dosage form. Semisolid dosage forms were prepared using a mixture of CZP/(polyethylene glycol 1500 (PEG))/(oleic acid (OA)) at the ratios of 1/39/0, 1/37/2 and 2/36/2 (w/w), named CZP1-PEG, CZP1-PEG-OA and CZP2-PEG-OA, respectively, and were evaluated in vitro and in vivo. No crystal of CZP was observed in CZP1-PEG-OA for at least 8 days, while CZP crystal appeared before administration for CZP2-PEG-OA. When a small volume of saline was added to CZP1-PEG-OA just before the oral cavity administration, more than 80% (w/w) was found to exist in the soluble form. Each semisolid dosage form (40 mg) was administered to the oral cavity in rats, and CZP 1 mg suspension in 0.5% (w/v) sodium carboxymethylcellulose aqueous solution was administered into rat stomach as a control. CZP1-PEG-OA gave the plasma concentrations of more than 5 ng/ml and 12 ng/ml at 30 min and 1 h after administration, respectively, which might be near the plasma levels effective for the suppression of epileptic seizures in human, while the plasma concentration was less than 5 ng/ml at 30 min or did not reach 10 ng/ml at 1 h for the other formulations. It is proposed that the semisolid dosage form CZP1-PEG-OA should be a possibly useful preparation for the antiepileptic or sedative medication.

  8. 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.

  9. Hematological and biochemical changes due to short-term oral administration of imidacloprid

    OpenAIRE

    Balani, Tarun; Agrawal, Seema; A M Thaker

    2011-01-01

    Subacute toxicity of repeated (28 day) oral administration of imidacloprid in male White Leghorn (WLH) chicks was assessed. One hundred and twenty-five birds were divided into five groups, with each group containing 25 birds. The birds of group C1 were given no treatment and served as control. Group C2 was administered groundnut oil (1 ml/kg) and served as control (vehicle). Group I1 was given 1/40th of apparent LD50 (ALD50) (1.25 mg/kg), and group I2 was put on 1/30th of ALD50 (1.67 mg/kg), ...

  10. Scintigraphic localization of lymphatic leakage site after oral administration of iodine-123-IPPA.

    Science.gov (United States)

    Kettner, B I; Aurisch, R; Rückert, J C; Sandrock, D; Munz, D L

    1998-12-01

    Chylothorax can occur secondary to traumatic lesions of the thoracic duct caused by chest injuries, surgical procedures involving the pleural space, neoplasms or malformations of the lymphatics. Lymphatic leakage sites were localized by scintigraphy after oral administration of the 123I-labeled long-chain fatty acid derivative iodophenyl pentadecanoic acid (IPPA). We report on three patients with different lymphatic leakage sites and on one normal control subject. IPPA scintigraphy localized the lymphatic leakage site correctly in all three patients. In two of them, the method even guided the successful surgical treatment of the leakage. This approach is suitable for detecting lymphatic leakages of intestinal origin.

  11. Adrenal insufficiency secondary to inappropriate oral administration of topical exogenous steroids presenting with hypercalcaemia.

    Science.gov (United States)

    Bhatti, Rahila Sarwar; Flynn, Michael D

    2012-06-21

    A 59-year-old Caucasian gentleman presented with malaise, fatigue and proximal muscle weakness. He had history of long-standing roseate psoriasis treated with topical clobetasol propionate (dermovate). On admission, he had significant postural hypotension, and hypercalcaemia. Endocrinological investigation revealed hypercalcaemia, a serum cortisol of <30 nmol/l, a flat short synacthen test and undetectable adrenocorticotropic hormone. He was treated with hydrocortisone. The abrupt withdrawal of the topical steroids by the patient precipitated the addisonian crisis. Further enquiry documented inappropriate oral administration of clobetasol for more than 10 years in addition to prescribed topical usage.

  12. 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

  13. Effects of Repeated Oral Administration of Pazufloxacin Mesylate and Meloxicam on the Antioxidant Status in Rabbits

    Science.gov (United States)

    Khan, Adil Mehraj; Rampal, Satyavan

    2014-01-01

    Prolonged antibiotic and antiinflammatory therapy for complicated infections exposes the body to xenobiotics that can produce several adverse effects for which oxidative damage is the proposed underlying mechanism. In this context, we evaluated the effect of pazufloxacin, a fluoroquinolone antimicrobial, and meloxicam, a nonsteroidal antiinflammatory drug, on antioxidant parameters and lipid peroxidation in rabbits after oral administration for 21 d. Reduced glutathione levels were significantly decreased in rabbits (n = 4 per group) given pazufloxacin, meloxicam, or their combination. In addition, glutathione peroxidase activity was induced in the rabbits treated with pazufloxacin only. Administration of pazufloxacin and meloxicam, as single agents as well as in combination, produced significant lipid peroxidation compared with levels in untreated controls. In conclusion, both pazufloxacin and meloxicam potentially can induce oxidative damage in rabbits. PMID:25199097

  14. 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...

  15. Protection of oral or intestinal candidiasis in mice by oral or intragastric administration of herbal food, clove (Syzygium aromaticum).

    Science.gov (United States)

    Taguchi, Yuuki; Ishibashi, Hiroko; Takizawa, Toshio; Inoue, Shigeharu; Yamaguchi, Hideyo; Abe, Shigeru

    2005-01-01

    We examined the effect of a clove (Syzygium aromaticum) administered by two different routes on Candida albicans growth, using a murine oral candidiasis model. When the clove preparation was administered into the oral cavity of Candida-infected mice, their oral symptoms were improved and the number of viable Candida cells in the cavity was reduced. In contrast, when the clove preparation was administered intragastrically, oral symptoms were not improved, but viable cell numbers of Candida in the stomach and feces were decreased. These findings demonstrate that oral intake of an herbal food, clove, may suppress the overgrowth of C. albicans in the alimentary tract including the oral cavity.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Effects of continuous oral administration of phenylbutazone on biomarkers of cartilage and bone metabolism in horses.

    Science.gov (United States)

    Fradette, Marie-Eve; Céleste, Christophe; Richard, Hèléne; Beauchamp, Guy; Laverty, Sheila

    2007-02-01

    To evaluate the effects of continuous oral administration of phenylbutazone on serum and synovial fluid biomarkers of skeletal matrix metabolism in horses. 11 adult female horses without clinical or radiographic evidence of joint disease. Horses were randomly assigned to control or treatment groups. Phenylbutazone was administered orally twice daily at a dose of 4.4 mg/kg for 3 days to the treatment group and subsequently at a dose of 2.2 mg/kg for 7 days. Serum and radiocarpal synovial fluid samples were obtained at baseline and thereafter at regular intervals for 4 weeks. Biomarkers of cartilage aggrecan synthesis (chondroitin sulfate 846) and type II collagen synthesis (procollagen type II C-propeptide) and degradation (collagen type II cleavage) were assayed. Biomarkers of bone synthesis (osteocalcin) and resorption (C-terminal telopeptide of type I collagen) were also measured. No significant differences were found between control and treatment groups or temporally for the biomarkers chondroitin sulfate 846, procollagen type II C-propeptide, collagen type II cleavage, and C-terminal telopeptide of type I collagen in serum or synovial fluid. A significant increase in osteocalcin concentration occurred in synovial fluid during treatment in the treated group. No treatment effect was detected for serum osteocalcin concentration. Results suggested that continuous phenylbutazone administration at recommended doses altered some biomarkers in healthy equine joints after short periods of administration. Increased osteocalcin concentration may indicate an undetermined anabolic effect of phenylbutazone administration on periarticular bone or transient induction of osteogenesis in articular chondrocytes or a mesenchymal subpopulation of synoviocytes.

  18. 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...

  19. The interpersonal needs questionnaire with a shortened response scale for oral administration with older adults.

    Science.gov (United States)

    Parkhurst, Kimberly A; Conwell, Yeates; Van Orden, Kimberly A

    2016-01-01

    The purpose of this paper is to examine the psychometric properties and construct validity of the interpersonal needs questionnaire (INQ) using a modified three-point response scale for oral administration with older adults. In-home interviews were conducted with 269 participants aged 60 and older who were completing an eligibility interview for a randomized control trial. The INQ was administered orally, as were measures of social support, death and suicide ideation, and meaning in life. A confirmatory factor analysis demonstrated acceptable fit, with all of the items loading significantly onto the associated latent variable of thwarted belongingness or perceived burdensomeness. Construct validity of the measure was supported through an examination of discriminant validity using constructs hypothesized by the interpersonal theory of suicide to be related to the measured constructs, including social support and social integration for thwarted belongingness, social worth and death ideation for perceived burdensomeness, and meaning in life and suicide ideation for both. The INQ yields reliable and valid scores of thwarted belongingness and burdensomeness when administered orally using a shortened response scale with older adults. These results help establish the measure as a valuable and practical tool for use in the field of late-life suicide prevention.

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

    Science.gov (United States)

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

    2016-08-01

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

  1. Influence of Particle Geometry on Gastrointestinal Transit and Absorption following Oral Administration.

    Science.gov (United States)

    Li, Dong; Zhuang, Jie; He, Haisheng; Jiang, Sifan; Banerjee, Amrita; Lu, Yi; Wu, Wei; Mitragotri, Samir; Gan, Li; Qi, Jianping

    2017-12-13

    Geometry has been considered as one of the important parameters in nanoparticle design because it affects cellular uptake, transport across the physiological barriers, and in vivo distribution. However, only a few studies have been conducted to elucidate the influence of nanoparticle geometry in their in vivo fate after oral administration. This article discloses the effect of nanoparticle shape on transport and absorption in gastrointestinal (GI) tract. Nanorods and nanospheres were prepared and labeled using fluorescence resonance energy transfer molecules to track the in vivo fate of intact nanoparticles accurately. Results demonstrated that nanorods had significantly longer retention time in GI tract compared with nanospheres. Furthermore, nanorods exhibited stronger ability of penetration into space of villi than nanospheres, which is the main reason of longer retention time. In addition, mesenteric lymph transported 1.75% nanorods within 10 h, which was more than that with nanospheres (0.98%). Fluorescent signals arising from nanoparticles were found in the kidney but not in the liver, lung, spleen, or blood, which could be ascribed to low absorption of intact nanoparticles. In conclusion, nanoparticle geometry influences in vivo fate after oral delivery and nanorods should be further investigated for designing oral delivery systems for therapeutic drugs, vaccines, or diagnostic materials.

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

    Directory of Open Access Journals (Sweden)

    Victoria A. Meliopoulos

    2016-11-01

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

  3. ANTI DIABETIC EFFECT OF ORAL ADMINISTRATION OF CINNAMON IN WISTAR ALBINO RATS

    Directory of Open Access Journals (Sweden)

    S Kumar

    2013-09-01

    Full Text Available Background: The present study was undertaken with an objective to observe effectiveness of oral administration of cinnamon extract to hyperglycemic induced rats using alloxan. Male and female Wistar Rats were injected with alloxan to induce hyperglycemia.Methods: This is an experimental study to determine whether cinnamon has an ability to combat hyperglycemic rats. Blood glucose was estimated by GOD-PAP method using diagnostic kit supplied by Agappe diagnostics, Maharashtra.Results: The present experimental study provides further evidence that oral administration of Cinnamon extract for 21 days produced a significant decrease in the blood glucose level in the model of alloxan induced diabetes rats.Conclusion: From this study, we can conclude that the oraladministration of Cinnamon extracts have beneficial effect on blood glucose levels. However further pharmacological and biochemical investigations will clearly elucidate the mechanism of action and helpful in projecting these plant extracts as a therapeutic target in diabetes research.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Oral administration of antioxidants improves skin wound healing in diabetic mice.

    Science.gov (United States)

    Pessoa, Ana Flávia Marçal; Florim, Juliana Costa; Rodrigues, Hosana Gomes; Andrade-Oliveira, Vinicius; Teixeira, Simone A; Vitzel, Kaio Fernando; Curi, Rui; Saraiva Câmara, Niels Olsen; Muscará, Marcelo N; Lamers, Marcelo Lazzaron; Santos, Marinilce Fagundes

    2016-11-01

    Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b + and Ly6G + cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG + /CD206 - macrophages whereas CD206 + /MIG - macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia. © 2016 by the Wound Healing Society.

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

    Science.gov (United States)

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

    2014-01-01

    To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  7. Oral administration of submerged cultivated Grifola frondosa enhances phagocytic activity in normal mice.

    Science.gov (United States)

    Wang, Lisu; Ha, Choi-Lan; Cheng, Tso-Lin; Cheng, Su-Yun; Lian, Tzi-Wei; Wu, Ming-Jiuan

    2008-02-01

    Grifola frondosa fruiting body (Maitake) has been used as a dietary supplement due to its antitumour and immunomodulatory properties. The aim of this study was to evaluate the immunomodulatory effects of orally administered submerged cultivated G. frondosa mixture, including both mycelium and culture broth, in a healthy murine model. Composition analyses showed that submerged cultivated G. frondosa mixture contained only 32.48% carbohydrate, which was less than half of fruiting bodies. The content of adenosine, a potential immunomodulatory agent in medicinal mushrooms, was 2.8 mg g(-1). After feeding 8-week-old female BALB/cByJ mice with AIN-93G diet containing 0% (C), 1% (G1), 3% (G3) or 5% (G5) (wt/wt) G. frondosa mixture for 31 days, neither body weight nor the outward appearance of organs showed any significant difference among different diet groups. Splenocyte subpopulation, mitogen-activated cytokine release and splenic NK activity were not affected by G. frondosa administration, either. On the other hand, the phagocytic activity was enhanced in leucocytes of groups G3 and G5, without exerting detectable levels of serum proinflammatory cytokines. These results suggested that oral administration of submerged cultivated G. frondosa mixture may enhance host innate immunity against foreign pathogens without eliciting adverse inflammatory response.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism.

    Science.gov (United States)

    Beluche, L A; Bertone, A L; Anderson, D E; Rohde, C

    2001-12-01

    To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1beta in articular cartilage explants of horses. 11 healthy 1- to 2-year-old horses. Horses were randomly assigned to the control (n = 5) or treated group (4.4 mg of phenylbutazone/kg of body weight, p.o., q 12 h; n = 6). Articular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment (day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with recombinant human interleukin-1beta (IL-1beta; 0.1 ng/ml). On day 0, proteoglycan synthesis was significantly less in cartilage explants cultured in IL-1beta, compared with medium alone. Mean proteoglycan synthesis in explants collected on days 14 and 30 was significantly less in treated horses, compared with controls. However, incubation of explants from treated horses with IL-1beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentration were not detected between or within groups. Oral administration of phenylbutazone for 14 days significantly decreased proteoglycan synthesis in articular culture explants from healthy horses to a degree similar to that induced by in vitro exposure to IL-1beta. Phenylbutazone should be used judiciously in athletic horses with osteoarthritis, because chronic administration may suppress proteoglycan synthesis and potentiate cartilage damage.

  10. 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

  11. Oral administration of Lactobacillus gasseri SBT2055 is effective for preventing influenza in mice.

    Science.gov (United States)

    Nakayama, Yosuke; Moriya, Tomohiro; Sakai, Fumihiko; Ikeda, Noriko; Shiozaki, Takuya; Hosoya, Tomohiro; Nakagawa, Hisako; Miyazaki, Tadaaki

    2014-04-10

    The Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with properties such as bile tolerance and ability to improve the intestinal environment. In this study, we established that the oral administration of LG2055 exhibits efficacy to protect mice infected with the influenza virus A/PR8. The body weight losses were lower with the LG2055 administration after the PR8 virus infection. At 5 days after the infection, the virus titer was significantly decreased as was the amount of produced IL-6 in the lung tissue, the number of total cells in the bronchoalveolar lavage fluid was reduced by the LG2055 administration. The expression of the Mx1 and Oas1a genes, critical for the viral clearance in the lung tissues was increased by the pre-treatment with LG2055. These findings suggest that the LG2055 administration is effective for the protection against influenza A virus infection by the down-regulation of viral replication through the induction of antiviral genes expression.

  12. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  14. Administration of adjuvant oral tegafur/uracil chemotherapy post hepatocellular carcinoma resection: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mitsuru Ishizuka

    2016-07-01

    Conclusion: Peroral UFT administration fails to prolong the recurrence-free rates and overall survival rates, in comparison with surgery alone. However, oral administration of UFT may improve the survival of HCC patients when the levels of TS and DPD mRNA are low in the tumor tissue.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Xinhuan Wan

    2014-12-01

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

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

  18. 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. © 2015 John Wiley & Sons Ltd.

  19. Tablets based on compressed zein microspheres for sustained oral administration: design, pharmacokinetics, and clinical study.

    Science.gov (United States)

    Gong, Sheng-Ju; Sun, Shi-Xuan; Sun, Qing-Shen; Wang, Jin-Ye; Liu, Xin-Ming; Liu, Guo-Yan

    2011-08-01

    In our previous study, we reported a novel tablet based on compressed zein microspheres as a universal drug delivery system using the hydrophobic protein zein, which shows zero-order release in the presence of pepsin. However, this formulation had difficulty with disintegration under physiological conditions within 48 h, and thus could not be used directly for oral administration. In the present study, a formulation of ivermectin (IVM) tablets based on compressed zein microspheres was improved as a new dosage form. The plasma disposition pharmacokinetics of IVM tablets based on compressed zein microspheres after oral administration was studied over a 7-day period with six dogs (Canis familiaris), using a commercial IVM tablet (5 mg/piece, Yilijia(®) ) as a control. Clinical efficacy was tested using 270 dogs presented as veterinary patients for the treatment of demodicidosis. A formulation with disintegration time within 15 min could be obtained. The acquired C( max), T(max), and AUC were 9.89 ± 0.34 ng/mL, 11.33 ± 2.63 h, and 883.87 ng h/mL for IVM tablets based on compressed zein microspheres and 9.64 ± 1.05 ng/mL, 7.26 ± 2.09 h, and 666.30 ng h/mL for Yilijia(®), respectively. The bioavailability of the tablets based on compressed zein microspheres was 132.65% that of Yilijia( ®). Efficacy for the dogs in all the IVM tablets based on compressed zein microspheres-treated groups reached 100% at 7, 14, and 21 days post administration.

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

    Directory of Open Access Journals (Sweden)

    Xiang-Shan Tan

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

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

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Moloy Kumar Bhar

    2010-12-01

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

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

    Science.gov (United States)

    Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina

    2009-11-03

    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 empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84-day regimen that

  4. Methotrexate efficacy and tolerability after switching from oral to subcutaneous route of administration in juvenile idiopathic arthritis.

    Science.gov (United States)

    Żuber, Zbigniew; Turowska-Heydel, Dorota; Sobczyk, Małgorzata; Banach-Górnicka, Marta; Rusnak, Katarzyna; Piszczek, Anna; Mężyk, Elżbieta

    2016-01-01

    Methotrexate (MTX) is one of the most frequently used, highly effective disease-modifying drugs in juvenile idiopathic arthritis (JIA) therapy. The drug can be administered orally or subcutaneously, but the efficacy and tolerance of these two routes of administration raise doubts in JIA patients. The aim of the study was to evaluate MTX efficacy and tolerability after switching from the oral to the subcutaneous route of administration in children with JIA. A single-centre, questionnaire-based assessment of MTX efficacy and tolerance in 126 unselected JIA patients with longer than 6 months of follow-up was performed. In all patients, MTX was initially administered orally. The response to MTX treatment was analysed according to American College of Rheumatology (ACR) paediatric criteria. Six-month MTX therapy was effective (ACR score ≥ 30) in 83 children (65.9%). The oral route of MTX administration was changed to subcutaneous in 32 patients after a mean period of 14 months due to intolerance (n = 20) or reluctance to take the oral formulation (n = 12). This group of children was significantly younger (p = 0.02) but did not differ from the group of children that continued oral treatment in other aspects, including MTX dose. Six months after switching from oral to subcutaneous MTX the ACR score remained unchanged. Three children (9.4%) still reported symptoms of drug intolerance. The switch from oral to subcutaneous MTX may increase the response rate in JIA patients with intolerance of its oral formulation. The reluctance to take oral MTX can be anticipated in early childhood, and should be considered in the individualization of therapy, having also in mind the lower risk of severe gastrointestinal adverse drug reactions.

  5. 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.

  6. Anabolic and androgenic activity of 19-norandrostenedione after oral and subcutaneous administration--analysis of side effects and metabolism.

    Science.gov (United States)

    Parr, M K; Laudenbach-Leschowsky, U; Höfer, Nicola; Schänzer, W; Diel, P

    2009-07-24

    One of the most frequently misused steroid precursors (prohormones) is 19-norandrostenedione (estr-4-ene-3,17-dione, NOR). Recently we have show that NOR stimulates skeletal muscle growth after s.c. administration in a highly selective manner but exhibits only weak androgenic activity in rats. Because most abusers take NOR orally, the aim of this study was to compare the anabolic and androgenic potency of NOR between s.c. and oral application. Orchiectomised rats were treated with NOR either s.c. (1 mg/kg BW/day) or orally (0.1, 1 and 10 mg/kg BW/day). The tissue weights of the levator ani, the seminal vesicle and the prostate were analysed to determine the anabolic and androgenic activity. Heart and liver wet weights were examined to identify side effects. Serum concentrations of NOR and its metabolite nandrolone (NT) were determined. GCMC analysis revealed that free and glucuronidated NOR and NT were detectable in the serum after oral and s.c. administration and that NOR was converted to NT in comparable amounts independent of the route of administration. In agreement to our previous study s.c. application of NOR stimulates skeletal muscle growth but has only weak androgenic effects. In contrast, after oral administration of NOR neither stimulation of the prostate nor the levator ani could be observed in the doses administered in this study. Interestingly, and in contrast to s.c. treatment, oral administration of NOR resulted in a dose-dependent decrease of body weight. In summary, oral administration of NOR, at least in the rat, seems to be a very ineffective strategy for stimulating skeletal muscle mass increases but may be associated with side effects.

  7. Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Sadakane, Kaori; Ichinose, Takamichi; Takano, Hirohisa; Yanagisawa, Rie; Koike, Eiko

    2014-02-01

    Subcutaneous injection of low dose of phthalates causes adjuvant effects on immunoglobulin production. Moreover, intraperitoneal injection of di-(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) at doses lower than the no-observed-adverse-effect level (NOAEL) causes aggravation of atopic dermatitis-like skin lesions (ADSLs) in mouse models. However, the effects of oral exposure to these phthalates, including their effect on atopic dermatitis (AD) symptoms, remain unclear. To investigate the effects of oral administration of DEHP and DINP at doses lower than the NOAEL on AD in an NC/Nga mouse model. NC/Nga mice were subcutaneously injected with mite-allergen (Dermatophagoides pteronyssinus) to induce ADSLs and orally administered varying doses of DEHP (0, 8.3, 166.3 or 3325 µg/animal) or DINP (0, 6.6, 131.3 or 2625 µg/animal) once a week for four weeks. Skin disease symptomatology was subsequently evaluated and immunoglobulin production levels in serum and inflammatory cytokine levels in lesion sites were measured. Oral administration of low doses of both DEHP and DINP tended to increase infiltration of eosinophils; degranulation of mast cells and local expression of inflammatory cytokines, interleukin-13 and macrophage inflammatory protein-1 alpha in subcutaneous tissue, whereas DINP administration tended to aggravate allergen-induced ADSL production. Oral administration of both DEHP and DINP at doses lower than the NOAEL tends to increase the allergic response in animal AD models, but only DINP administration slightly aggravates allergen-induced ADSL production.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Daniela Gioeni

    2017-05-01

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

  10. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

  12. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

    Directory of Open Access Journals (Sweden)

    Michelle Dang

    2016-07-01

    Full Text Available Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1 and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases.

  13. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies.

    Science.gov (United States)

    Dang, Michelle; Henderson, Rachel E; Garraway, Levi A; Zon, Leonard I

    2016-07-01

    Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAF(V600E) inhibitor, Vemurafenib, in adult zebrafish harboring BRAF(V600E) melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. © 2016. Published by The Company of Biologists Ltd.

  14. Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration.

    Science.gov (United States)

    Cho, Wan-Seob; Kang, Byeong-Cheol; Lee, Jong Kwon; Jeong, Jayoung; Che, Jeong-Hwan; Seok, Seung Hyeok

    2013-03-26

    The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. TiO₂ nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO₂ nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. Compared with TiO₂ nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO₂ nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.

  15. 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). Copyright © 2013 John Wiley & Sons, Ltd.

  16. Influence of acute and subchronic oral administration of dehydroepiandrosterone (DHEA) on nociceptive threshold in rats.

    Science.gov (United States)

    Gąsińska, Emilia; Bujalska-Zadrożny, Magdalena; Sar, Monika; Makulska-Nowak, Helena

    2012-01-01

    Dehydroepiandrosterone (DHEA), a neurosteroid, is known to be the most abundant hormone in the human body. Its role in the central nervous system has not been well defined. Previous studies indicate that DHEA is synthesized in the spinal cord and plays an important role in pain modulation. In the present study, we investigated the effect of DHEA on pain threshold in rats after both acute and subchronic treatment. Rats were orally administered with DHEA at a dose of 10 mg/kg once daily and the pain threshold was measured with mechanical and thermal stimuli. After acute treatment, DHEA exhibited pronociceptive effects which lasted up to 150 min. After subchronic administration, DHEA showed an opposite effect by elevating the pain threshold. The results suggest that DHEA could be indicated as a drug to improve treatment of chronic pain disorders.

  17. Egg albumin microspheres containing paracetamol for oral administration. I. In vitro characterization.

    Science.gov (United States)

    Torrado, J J; Illum, L; Cadorniga, R; Davis, S S

    1990-01-01

    Different egg albumin microsphere systems for oral administration of paracetamol were prepared by the emulsion and capillary extrusion methods. The size of the microspheres depended on the method used to produce the microcapsules and also the size of the crystals of paracetamol. The effect of the following factors on in vitro dissolution were studied: different denaturation processes, variation in the ratio of paracetamol to albumin, size of microspheres, remnant oil in the microspheres, and the coating of the microspheres with membranes of polymethacrylates (Eudragit). The most important factors to control the release of paracetamol from the microspheres were the denaturation process and the use of waxes and membranes to delay the release of paracetamol from the microspheres. The egg albumin microspheres were very porous and permeable to water and thus the release of the paracetamol from the matrix was usually fast unless the microspheres were suitably coated, with, for example, Eudragit RL or RS.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV) inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream. This class has yet to be investigated...... 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......AMP-response element binding protein (CREB) system was significantly more pronounced (~1.5-fold, p Conversely, apoptotic tone (alpha-spectrin fragmentation, Bcl-2...

  19. 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. © 2015 John Wiley & Sons Ltd.

  20. Oral administration of Saccharomyces cerevisiae UFMG A-905 prevents allergic asthma in mice.

    Science.gov (United States)

    Fonseca, Vanessa M B; Milani, Thamires M S; Prado, Rafael; Bonato, Vania L D; Ramos, Simone G; Martins, Flaviano S; Vianna, Elcio O; Borges, Marcos de C

    2017-07-01

    The prevalence of asthma has increased in communities that adopt a Western lifestyle and become more urbanized. Probiotics may be effective in the prevention of allergic diseases, such as asthma. The aim of the current study was to examine the effects of Saccharomyces cerevisiae UFMG A-905 in an allergic model of asthma. Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally, 1 week apart and challenged with OVA intranasally for 3 days. Mice were daily treated with S. cerevisiae UFMG A-905 via gavaging needle 10 days before OVA sensitization and during challenges. After challenge, in vivo lung function was measured, and bronchoalveolar lavage (BAL) and lung inflammation were assessed. Oral treatment with S. cerevisiae UFMG A-905 significantly decreased airway hyperresponsiveness, total cell number and the influx of eosinophils to the airway, inflammatory cell in the lung, mucus expression in epithelial cells and the levels of IL-4, IL-5 and IL-13. Additionally, S. cerevisiae UFMG A-905 restored the levels of IL-10 and interferon (IFN)-gamma, and increased the levels of IL-17A. Oral administration of S. cerevisiae UFMG A-905 prevented the development of major asthma-like characteristics in a mouse model. © 2017 Asian Pacific Society of Respirology.

  1. Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses.

    Science.gov (United States)

    Buntenkötter, Kathrin; Osmers, Maren; Schenk, Ina; Schänzer, Wilhelm; Machnik, Marc; Düe, Michael; Kietzmann, Manfred

    2017-01-19

    Although acetylsalicylic acid (ASA) is not frequently used as a therapeutic agent in horses, its metabolite SA is of special interest in equestrianism since it is a natural component of many plants used as horse feed. This led to the establishment of thresholds by horse sport organizations for SA in urine and plasma. The aim of this study was to investigate plasma and urine concentrations of salicylic acid (SA) after oral administration of three different single dosages (12.5 mg/kg, 25 mg/kg and 50 mg/kg) of acetylsalicylic acid (ASA) to eight horses in a cross-over designed study. In the 12.5 mg/kg group, SA concentrations in urine peaked 2 h after oral administration (2675 μg/mL); plasma concentrations peaked at 1.5 h (17 μg/mL). In the 25 mg/kg group, maximum concentrations were detected after 2 h (urine, 2785 μg/mL) and 1.5 h (plasma, 23 μg/mL). In the 50 mg/kg group, maximum concentrations were observed after 5 h (urine, 3915 μg/mL) and 1.5 h (plasma, 45 μg/mL). The plasma half-life calculated for SA varied between 5.0 and 5.7 h. The urine concentration of SA fell below the threshold of 750 μg/mL (set by the International Equestrian Federation FEI and most of the horseracing authorities) between 7 and 26 h after administration of 12.5 and 25 mg/kg ASA and between 24 and 36 h after administration of 50 mg/kg ASA. For ASA, IC50 were 0.50 μg/mL (COX-1) and 5.14 μg/mL (COX-2). For salicylic acid, it was not possible to calculate an IC50 for either COX due to insufficient inhibition of both cyclooxygenases. The established SA thresholds of 750 μg//mL urine and 6.5 μg/mL plasma appear too generous and are leaving space for misuse of the anti-inflammatory and analgetic compound ASA in horses.

  2. Edible Camphor-induced Histopathological Changes in Hippocampus and Cerebral Cortex Following Oral Administration into Rats

    Directory of Open Access Journals (Sweden)

    Oluwatobi T Somade

    2017-03-01

    Full Text Available Introduction: Raw edible camphor (EC, and as component of herbal infusions are widely used to treat pile, back pain, erectile dysfunction, and as an aphrodisiac especially in preparation for sexual intercourse by men. It has been traced in umbilical cord, blood, fetal, adipose, and other tissues including brain, where it bioaccumulates. Methods: The study, therefore, investigated the possible histopathological changes in brain, heart, and spleen that may result following EC administration in rats. Thirty animals were used for the study and were divided into six groups of five rats each. Group I animals served as normal control, Group II animals served as vehicle control and were orally administered 6 mL/kg corn oil daily for 7 days, while Groups III-VI animals were orally administered 1, 2, 4, and 6 g/kg EC for 7 days daily. Results and Conclusions: Following the administrations of various doses of EC, the histopathological changes seen in the cerebral cortex of the brain include mild submeningeal spongiosis, mild diffuse spongiosis of the parenchyma, a very mild diffuse gliosis, and presences of gitter cells, while in hippocampus, there were mild diffuse gliosis and disruption of the progression of the hippocampal horns, as well as foci of spongiosis around the hippocampal horns, and neuronal cells have open faced nuclei. No effect was seen in heart and spleen except 4 g/kg of EC that revealed moderate diffuse congestion in spleen only. In conclusion, EC may not have any toxic effects on the cardiac and splenic cells, but had toxic effects on the brain hippocampus and cerebral cortex, and may lead to brain cell damage. [J Interdiscipl Histopathol 2017; 5(1.000: 7-11

  3. Effects of oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs.

    Science.gov (United States)

    Asadi, Faezeh; Rajaei, Seyed Mehdi; Golabdar, Salar

    2016-09-01

    To determine the effects of short-term oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs. Thirty-two healthy adult Abyssinian guinea pigs were used in this study. One day before the start of the trial, the pretreatment baseline phenol red thread test (PRTT) values were recorded. Sixteen guinea pigs in the treated group received 25 mg/kg trimethoprim-sulfamethoxazole orally twice a day for 14 days. The other sixteen guinea pigs were used as untreated controls and received a placebo during the study. All the ophthalmic tests were performed without chemical restraint. PRTT values were evaluated in both eyes of all the guinea pigs using a commercial PRTT strip of a single lot number on days 0 (baseline), 15, and 21 after starting the trial. The pretreatment baseline mean ± SD PRTT values for the treatment and control groups were 11.12 ± 3.82 mm/15 s and 11.93 ± 2.73 mm/15 s, respectively. After 14 days of drug administration, the mean ± SD PRTT values for the treatment and control groups were 10.87 ± 3.11 mm/15 s and 13.00 ± 2.47 mm/15 s, respectively. On Day 21, the mean ± SD PRTT values for the treatment and control groups were 12.62 ± 4.05 mm/15 s and 12.87 ± 2.99 mm/15 s, respectively. Significant decreases in the PRTT values, compared with the pretreatment baseline values, were not observed in the treatment group on Day 15 (P = 0.14) and Day 21 (P = 0.31). Trimethoprim-sulfamethoxazole did not decrease tear production in the guinea pigs in this study. © 2015 American College of Veterinary Ophthalmologists.

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

    Science.gov (United States)

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

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  5. Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.

    Directory of Open Access Journals (Sweden)

    Norio Sasaoka

    Full Text Available Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein, by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.

  6. Oral Administration of Lipopolysaccharide of Acetic Acid Bacteria Protects Pollen Allergy in a Murine Model.

    Science.gov (United States)

    Amano, Satoko; Inagawa, Hiroyuki; Nakata, Yoko; Ohmori, Masaki; Kohchi, Chie; Soma, Gen-Ichiro

    2015-08-01

    Lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, is known to possess strong immune-regulatory activity. We have found and reported the existence of biologically-active LPS in acetic acid bacteria. The LPS shows Limulus-positive activity and activation of macrophages to produce nitric oxide and tumor necrosis factor. In this study, we investigated the anti-allergic effect of an orally-administrated acetic acid bacteria extract containing LPS; the cedar pollinosis model was used. Acetic acid bacteria were isolated from various fruits by Nodai kaihen medium. Then, the anti-allergic effect of acetic acid bacteria extracts was investigated. BALB/c mice were immunized with a mixture of cedar pollen and alum into their peritoneal cavity; they also received additional immunizations of pollen to nasal cavity. After immunizing the mice with pollen into their nasal cavity to trigger an allergic reaction, the frequency of nose scratching was counted for 5 min. The bacteria were cultured and prepared and the water-extract contained about 1-10 mg/ml of Limulus positive substances. The extract of acetic acid bacteria induced higher levels of interleukin (IL)-10 and FOXP3 mRNA expression in macrophages (RAW246.7 cell), as assessed by DNA microarray analysis. Oral administration of the acetic acid bacteria extract demonstrated significantly less scratching numbers than control water group with pollen immunization. These results showed that LPS in acetic acid bacteria has the potential to protect from an allergic reaction, especially from cedar pollinosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Science.gov (United States)

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

    2013-07-01

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

  8. Induced diarrhoea in horses. Part 2: Response to administration of an oral rehydration solution.

    Science.gov (United States)

    Ecke, P; Hodgson, D R; Rose, R J

    1998-03-01

    Hydration status, electrolyte balance and acid-base balance were studied in four adult standardbred geldings with castor oil-induced diarrhoea. The horses received an oral rehydration solution (ORS) at a point when signs consistent with mild decreases in effective circulating fluid volume were first detected. Within 1.5 h of ORS administration, all horses exhibited a significant metabolic acidosis. At this time, mean values for venous blood pH, [HCO3], and standard base excess were 7.264 +/- 0.011, 17.7 +/- 0.3 mmol L-1, and -8.2 +/- 0.4 mmol L-1, respectively. Throughout the duration of the study, plasma volume did not change significantly, despite a decreasing trend, which tended to recover towards normal values 8 h after administration of the ORS. Signs of abdominal discomfort were observed in all horses following the last of three doses of ORS (8-10 L) administered at 30 min intervals. Faecal fluid sodium concentration increased significantly with diarrhoea, and reached values fourfold those in normal horses, while faecal dry matter sodium concentration increased exponentially following the onset of clinical signs. Despite this increase in sodium concentration, faecal fluid remained hypotonic at all stages. Our findings suggest that, while ORS can help restore systemic fluid balance, several factors influence their effectiveness. Two likely factors identified in this study were the ionic composition of the ORS as well as the rate of administration. We concluded that the electrolyte composition of current ORS may not be ideal to treat diarrhoea in horses and that administration of 8-10 of ORS every 30 min via nasogastric tube may result in too rapid small intestinal transit to allow sufficient time for absorption.

  9. Collecting psychosocial self-report data in oral health research: impact of literacy level and computerised administration.

    Science.gov (United States)

    Randall, Cameron L; McNeil, Daniel W; Crout, Richard J; Weyant, Robert J; Marazita, Mary L

    2013-09-01

    In oral and other health research, participant literacy levels may impact the quality of data obtained through self-report (e.g., degree of data missingness). This study addressed whether computerized administration of a battery of psychosocial instruments used in an oral health disparities research protocol yielded more complete data than paper-and-pencil administration and aimed to determine the role of general literacy in differences in data missingness between administration types. Oral health data were obtained from 1,652 adolescent and adult participants who were administered a large questionnaire battery via either paper-and-pencil or tablet personal computer. Number of unanswered items for each participant was compared across administration mode. For a subset of 171 participants who were randomized to one of the administration modes, general literacy and satisfaction with the questionnaire experience also were assessed. Participants assigned to complete the oral health questionnaire battery via tablet PC were significantly more likely than those assigned to the paper-and-pencil condition to have missing data for at least one item (p < .001); however, for participants who had at least one missing item, paper-and-pencil administration was associated with a greater number of items missed than was tablet PC administration (p < .001). Across administration modes, participants with higher literacy level completed the questionnaire battery more rapidly than their lower literacy counterparts (p < .001). Participant satisfaction was similar for both modes of questionnaire administration (p ≥ .29). These results suggest that a certain type of data missingness may be decreased through the use of a tablet computer for questionnaire administration.

  10. A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

    Science.gov (United States)

    Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

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

    Science.gov (United States)

    Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

    2017-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

  12. Ether: a forgotten addiction.

    Science.gov (United States)

    Krenz, Sonia; Zimmermann, Grégoire; Kolly, Stéphane; Zullino, Daniele Fabio

    2003-08-01

    Among abused inhalants, ether has recently received little attention. The case of a patient suffering from ether dependence is reported. Whereas several features of DSM-IV dependence were fulfilled, no physical withdrawal signs were observed.

  13. Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men.

    Science.gov (United States)

    Schilling, Brian K; Hammond, Kelley G; Bloomer, Richard J; Presley, Chaela S; Yates, Charles R

    2013-10-04

    1,3-dimethylamylamine (DMAA) has been a component of dietary supplements and is also used within "party pills," often in conjunction with alcohol and other drugs. Ingestion of higher than recommended doses results in untoward effects including cerebral hemorrhage. To our knowledge, no studies have been conducted to determine both the pharmacokinetic profile and physiologic responses of DMAA. Eight men reported to the lab in the morning following an overnight fast and received a single 25 mg oral dose of DMAA. Blood samples were collected before and through 24 hours post-DMAA ingestion and analyzed for plasma DMAA concentration using high-performance liquid chromatography-mass spectrometry. Resting heart rate, blood pressure, and body temperature was also measured. One subject was excluded from the data analysis due to abnormal DMAA levels. Analysis of the remaining seven participants showed DMAA had an oral clearance of 20.02 ± 5 L∙hr⁻¹, an oral volume of distribution of 236 ± 38 L, and terminal half-life of 8.45 ± 1.9 hr. Lag time, the delay in appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes (0.14 ± 0.13 hr). The peak DMAA concentration for all subjects was observed within 3-5 hours following ingestion and was very similar across subjects, with a mean of ~70 ng∙mL⁻¹. Heart rate, blood pressure, and body temperature were largely unaffected by DMAA treatment. These are the first data to characterize the oral pharmacokinetic profile of DMAA. These findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15-30 times lower than those reported in case studies linking DMAA intake with adverse events. Finally, a single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature. NCT01765933.

  14. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects.

    Science.gov (United States)

    Kanaze, F I; Bounartzi, M I; Georgarakis, M; Niopas, I

    2007-04-01

    Hesperetin and naringenin, the aglycones of the flavanone glycosides hesperidin and naringin, occur naturally in citrus fruits. They exert interesting pharmacological properties such as antioxidant, anti-inflammatory, blood lipid and cholesterol lowering and are considered to contribute to health benefits in humans. However, no information is available on the pharmacokinetics of the citrus flavanones hesperetin and naringenin after their oral administration to humans as pure aglycones. Therefore, the objective of the present investigation was the evaluation of the pharmacokinetic parameters of hesperetin and naringenin in plasma and urine, after their single oral administration in humans in the form of solid dispersion capsules, and also to improve the absorption rate of flavanones by using aglycones rather than the naturally occurring glycosides. Six healthy volunteers received orally 135 mg of each compound, hesperetin and naringenin, under fasting conditions. Blood samples were collected at 14 different time points over a 12 h period. Urine was collected over 24 h, in five sequential timed intervals. Plasma and urine hesperetin and naringenin concentrations, after enzymatic hydrolysis of their conjugated forms, were measured using validated high-pressure liquid chromatography methods. Pharmacokinetic parameters for hesperetin and naringenin, such as C(max), T(max), AUC(0-t), AUC(0-infinity), CL/F, V/F, t(1/2), MRT, A(e), A(e)((0-24)), and R(max) were calculated from their plasma or urine concentrations. Pharmacokinetic analysis showed that both hesperetin and naringenin were rapidly absorbed and their concentrations in plasma observed 20 min after dosing and reached a peak in 4.0 and 3.5 h, respectively. The mean peak plasma concentration (C(max)) for hesperetin and naringenin were 825.78+/-410.63 ng/ml (2731.8+/-1358.4 nmol/l) and 2009.51+/-770.82 ng/ml (7386.6+/-2833.4 nmol/l), respectively and the mean AUC(0-infinity) values were 4846.20+/-1675.99 ng h/ml and

  15. 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 in hepato......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...

  16. 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 blood pressure of normal rats showed no significant changes during long-term 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.

  17. Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Alvarado-Vásquez, Noé; Lascurain, Ricardo; Cerón, Eduarda; Vanda, Beatriz; Carvajal-Sandoval, Guillermo; Tapia, Aurora; Guevara, Jorge; Montaño, Luis Felipe; Zenteno, Edgar

    2006-06-13

    Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (Pdiabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (Pcorporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.

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

    Directory of Open Access Journals (Sweden)

    C. GAVAN

    2009-10-01

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

  19. Effect of Oral Administration of Butyrivibrio fibrisolvens MDT-1 on Experimental Enterocolitis in Mice▿

    Science.gov (United States)

    Ohkawara, Sou; Furuya, Hideki; Nagashima, Kousuke; Asanuma, Narito; Hino, Tsuneo

    2006-01-01

    Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (109 CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture supernatant inhibited the growth of nine clinical isolates of Campylobacter jejuni and Campylobacter coli that could potentially cause enterocolitis. Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in colonic tissue, increased numbers of C. coli in the cecum, and decreased body weight gain. However, administration of MDT-1 to mice, prior to and during C. coli infection, reduced these effects. These results suggest that Campylobacter-induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic. PMID:16988006

  20. Effect of oral administration of Butyrivibrio fibrisolvens MDT-1 on experimental enterocolitis in mice.

    Science.gov (United States)

    Ohkawara, Sou; Furuya, Hideki; Nagashima, Kousuke; Asanuma, Narito; Hino, Tsuneo

    2006-11-01

    Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (10(9) CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture supernatant inhibited the growth of nine clinical isolates of Campylobacter jejuni and Campylobacter coli that could potentially cause enterocolitis. Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in colonic tissue, increased numbers of C. coli in the cecum, and decreased body weight gain. However, administration of MDT-1 to mice, prior to and during C. coli infection, reduced these effects. These results suggest that Campylobacter-induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic.

  1. Oral administration of Grifola frondosa polysaccharides improves memory impairment in aged rats via antioxidant action.

    Science.gov (United States)

    Chen, Zhaoxia; Tang, Yanan; Liu, Along; Jin, Xiaobao; Zhu, Jiayong; Lu, Xuemei

    2017-11-01

    Grifola frondosa is an edible/medicinal mushroom with great nutritional value and bioactivity. The present study was performed to evaluate the beneficial effect of polysaccharides isolated from Grifola frondosa on memory impairment in aged rats. 20-month-old rats were gavaged with Grifola frondosa polysaccharides (GFP) for 8 weeks. Morris Water Maze test revealed that GFP administration significantly improved memory impairment in aged rats. GFP supply was also found to attenuate age-associated changes of brain histology and ultrastructure observed by light microscopy and transmission electron microscopy. Moreover, the increase of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, as well as the decreased nitric oxide (NO) and malondialdehyde (MDA) levels, were consistent with the behavioral results. These findings indicated that oral administration of GFP could improve memory impairment via antioxidant action, and dietary supplementation with GFP may provide potential benefits on brain aging. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2007-12-15

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

  3. Evaluation of the safety of a combination of oral administration of phenylbutazone and firocoxib in horses.

    Science.gov (United States)

    Kivett, L; Taintor, J; Wright, J

    2014-08-01

    Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10-day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine-specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co-administration of phenylbutazone and firocoxib may cause renal disease. © 2013 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Science.gov (United States)

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

    2004-01-01

    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 C II and AA model + meloxicam + nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund’s adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. 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 meloxicam group were significantly less than those in AA rats (P meloxicam group compared with normal control (P meloxicam model and the curative effects of nasal CII (20 μg/kg) were shown to be more efficient than that of oral CII (20 μg/kg) both in AA model and in AA + meloxicam model (P < 0.05). CONCLUSION: Oral administration of CII shows the limited efficacy on arthritis in AA rats with intestinal lesions, and nasal administration of CII is more efficient than oral administration of CII to induce mucosal tolerance in AA rats. PMID:15457565

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

    OpenAIRE

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

    2011-01-01

    Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n=360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ9-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography– mass spectrometry with electron-impact ionization for THC,...

  7. Oral Administration of 17α-Methyltestosterone Increased Male Percentage of Freshwater Crayfish Cherax quadricarinatus

    Directory of Open Access Journals (Sweden)

    O. Carman

    2008-01-01

    Full Text Available Cherax quadricarinatus is one of freshwater crayfish species that has enormous potential for expanding its farming in future.  Application of monosex male culture using steroid sex hormone administration method during the period of sex differentiation or early developmental stage might be increased efficiency in farming.  This study was aimed to increase male of C. quadricarinatus by oral administration of diet containing 17α-methyltestosterone (MT towards production efficiency.  Two-week-old of Cherax quadricarinatus were fed ad libitum on diets containing various dose of MT, i.e., 25, 50, 75, 100 and 150 mg/kg diet or diet containing no MT as control, 3 times daily for 30 days.  After MT-treatment, crayfish were fed frozen Chironomus sp.  and shrimp diet.  Sex ratio, survival and growth rate (by length and weight were observed at the end of experiment.  Sex was determined by visual observation; the male sex organ is located at the fifth walking leg while the female is at the third.  Data was analyzed by F and BNT tests.  The results of study show that administration of MT was significantly changed the male ratio of crayfish.  Treatment dose of 50 mg/kg diet was effective to increase male sex percentage from 24.93% (control to be 59.96%. Growth was also significantly being improved, while survival rate was insignificant.  Thus, oral administration of MT is an effective way to increase male sex percentage of crayfish, although other methods and the time of hormone administration are needed to be verified to obtain maximal results. Keywords: monosex, 17α-methyltestosterone, sex reversal, Cherax quadricarinatus   ABSTRAK Salah satu jenis lobster air tawar yang berpotensi tinggi untuk dikembangkan usaha budidayanya adalah Cherax quadricarinatus. Aplikasi teknik budidaya tunggal kelamin (monoseks dengan metode pemberian hormon seks steroid yang diberikan pada saat diferensiasi kelamin atau masa perkembangan awal ikan diduga dapat

  8. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy.

    Science.gov (United States)

    Neuss, Michael N; Polovich, Martha; McNiff, Kristen; Esper, Peg; Gilmore, Terry R; LeFebvre, Kristine B; Schulmeister, Lisa; Jacobson, Joseph O

    2013-05-01

    In 2009, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) published standards for the safe use of parenteral chemotherapy in the outpatient setting, including issues of practitioner orders, preparation, and administration of medication. In 2011, these were updated to include inpatient facilities. In December 2011, a multistakeholder workgroup met to address the issues associated with orally administered antineoplastics, under the leadership of ASCO and ONS. The workgroup participants developed recommended standards, which were presented for public comment. Public comments informed final edits, and the final standards were reviewed and approved by the ASCO and ONS Boards of Directors. Significant newly identified recommendations include those associated with drug prescription and the necessity of ascertaining that prescriptions are filled. In addition, the importance of patient and family education regarding administration schedules, exception procedures, disposal of unused oral medication, and aspects of continuity of care across settings were identified. This article presents the newly developed standards.

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

    Directory of Open Access Journals (Sweden)

    Wenli Liu

    2016-09-01

    Full Text Available 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 physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim as a model drug and investigated the effect of age difference (2- and 9-month old on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim, the AUC0–24 h in 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim, the AUC0–24 h in 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC0–24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Menéndez R.

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-11-01

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

  14. Multiple-dose pharmacokinetics of ceftibuten after oral administration to healthy volunteers.

    Science.gov (United States)

    Bressolle, F; Galtier, M; Kinowski, J M; Goncalves, F; Edno, L; Panis, R; Gomeni, R

    1994-09-01

    The pharmacokinetics of ceftibuten in plasma and urine were investigated after oral administration. Twelve healthy subjects were treated orally twice daily with 400 mg of the drug for 7 days; on day 8, the subjects received a last dose of 400 mg of ceftibuten. Ceftibuten and its metabolite, the trans isomer of ceftibuten, were assayed in plasma and urine by a specific HPLC method with UV detection. Ceftibuten was rapidly absorbed, as evidenced by the mean time to the maximum observed cis-ceftibuten concentration of 2.4 h. To describe the drug intake process, a Weibull model was used. For the metabolite, the mean time to maximum concentration in plasma was 3.25 h. Mean values for the terminal half-life in plasma were 2.17 h for cis-ceftibuten and 3.19 h for trans-ceftibuten. The overall elimination half-life, tmax, and total and renal clearances of cis-ceftibuten were invariant with respect to duration of dosing. The area under the plasma concentration versus time curve from 0 to infinity and the Cmax of this drug were significantly higher on day 8 than the values predicted from the elimination half-life computed on day 1 of treatment and the dosing interval. The pharmacokinetic parameters of trans-ceftibuten were invariant with respect to duration of dosing. Ceftibuten was well tolerated; there were no clinically significant adverse clinical events. The results from the present study indicate that the levels of cis-ceftibuten in plasma as well as in urine remain above the MICs for susceptible organisms over the dosing interval.

  15. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice.

    Directory of Open Access Journals (Sweden)

    M Ujue Latasa

    Full Text Available BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA in Mdr2(-/- mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/- mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/- mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts. PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-13

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

  17. 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...

  18. Inappropriate glucagon response after oral compared with isoglycemic intravenous glucose administration in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Hare, Kristine J; Vilsbøll, Tina; Holst, Jens Juul

    2010-01-01

    that the inappropriate glucagon response to glucose in patients with type 1 diabetes occurs as a consequence of the oral administration way, suggesting a role of the gastrointestinal tract, possibly via glucagonotropic signaling from gut hormones (e.g., glucose-dependent insulinotropic polypeptide), in type 1 diabetic...

  19. Pharmacokinetics of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, after a single oral administration to pigs

    National Research Council Canada - National Science Library

    Lim, Jong-Hwan; Kim, Myoung-Seok; Hwang, Youn-Hwan; Song, In-Bae; Park, Byung-Kwon; Yun, Hyo-In

    2010-01-01

    Toltrazuril (TZR) is a triazine-based antiprotozoal agent. Following a single oral administration of TZR at 10 and 20 mg/kg to male pigs, the mean TZR concentration in plasma peaked at 4.24 and 8.18 microg/ml at 15.0...

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

    Directory of Open Access Journals (Sweden)

    Maaike van Putten

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Toshihiro Sashihara

    2008-01-01

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

  2. 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.

  3. Effect of Oral Administration of Bromelain on Postoperative Discomfort After Third Molar Surgery.

    Science.gov (United States)

    Ghensi, Paolo; Cucchi, Alessandro; Creminelli, Luca; Tomasi, Cristiano; Zavan, Barbara; Maiorana, Carlo

    2017-03-01

    The purpose of this prospective randomized controlled clinical trial was to evaluate the effect of oral administration of bromelain on discomfort after mandibular third molar surgery. Eighty-four consecutive patients requiring surgical removal of a single mandibular impacted third molar under local anesthesia were randomly assigned to receiving no drug (control group, Group A), postoperative 40 mg bromelain every 6 hours for 6 days (Group B), preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection (Group C), and preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection plus postoperative 40 mg bromelain every 6 hours for 6 days (Group D). Standardized surgical and analgesic protocols were adopted. Maximum interincisal distance and facial contours were measured at baseline and on postoperative days 2 and 7. Pain was measured objectively by counting the number of analgesic tablets required. Patient perception of the severity of symptoms was assessed with a follow-up questionnaire (PoSSe scale). On postoperative day 2, there was a statistically significant reduction in facial edema in both Groups C and D compared with the control group, but no statistically significant differences were observed between Group B and the control group. At evaluation on postoperative day 7, Group D showed a statistically significant reduction in postoperative swelling compared with the control group. The combined use of bromelain and dexamethasone (Group D) induced a statistically significant reduction in the total number of analgesic tablets taken after surgery compared with the control group. The treatment groups had a limited, nonsignificant effect on trismus when compared with the control group. Bromelain used singly showed moderate anti-inflammatory efficacy, reducing postoperative swelling, albeit not to any significant extent compared with no drug administration. The combined use of bromelain and dexamethasone sodium phosphate yielded

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

    Directory of Open Access Journals (Sweden)

    Temitayo O. Iji

    2013-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Alvaro eGarcía-Aviles

    2015-03-01

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

  6. Fluorescence and inmunohistological detection of estrogen receptors in dog testis and epidydimis after oral coumestrol administration.

    Science.gov (United States)

    Serrano, Hector; Perez-Rivero, Juan Jose; Martinez-Maya, Jose Juan; Aguilar-Setien, Alvaro; Perez-Martinez, Mario; Garcia-Suarez, Maria-Dolores

    2008-12-01

    Estrogens are well recognized as important hormones in male reproduction and act as ligands to alpha and beta estrogen receptors. Both estrogen receptors could interact with estrogen-mimicking compounds such as the fluorescent phytoestrogen coumestrol, which acts both in an agonist or antagonist fashion. To investigate the presence of Coumestrol-Estrogen Receptor complexes by fluorescence in testis and epididymis, its effect in the ER expression by immunostain in the same tissues and the effect of this binding in the testis histological characteristics. Adult healthy and sexually active dogs were assigned to either the experimental or control group .Coumestrol impregnated dog biscuits were given to each animal from the experimental group once a week for a 4 week period. The control group received a biscuit with no Coumestrol, also once a week and for the same period. Testis morphology, ER immunodetection, and coumestrol-receptor binding were evaluated. The experiment was done in the facilities of the Mexico City canine shelter. Animals were caged individually with food and water ad libitum and having at least two daily hours for exercise. Morphological alterations in testis after oral administration of coumestrol were detected. The main alterations include decreased germinal epithelium in tubule, and the loss of a continuous proliferation and differentiation gamete layer. Fluorescence signals in testis interstitial Leydig cells and epididymus indicating ER-coumestrol complexes were detected at the same points to those Immunohystochemically detected ER. Coumestrol administration induces testis alterations and coumestrol-ER complexes can be co-localized by binding-enhanced fluorescence and immunoprecipitation.

  7. Pharmacokinetics and antitumor efficacy of paclitaxel-cyclodextrin complexes loaded in mucus-penetrating nanoparticles for oral administration.

    Science.gov (United States)

    Calleja, Patricia; Espuelas, Socorro; Corrales, Leticia; Pio, Ruben; Irache, Juan M

    2014-07-01

    The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol). Formulations were prepared using the solvent displacement method. Subsequently, pharmacokinetics and organ distribution assays were evaluated after oral administration into C57BL/6J mice. In addition, antitumor efficacy studies were performed in a subcutaneous tumor model of Lewis lung carcinoma. PTX-loaded NPs displayed sizes between 190-300 nm. Oral NPs achieved drug plasma levels for at least 24 h, with an oral bioavailability of 55-80%. Organ distribution studies revealed that PTX, orally administered in NPs, underwent a similar distribution to intravenous Taxol(®) (Bristol-Myers Squibb, NJ, USA). For in vivo antitumor assays, oral strategy maintained a slower tumor growth than intravenous Taxol. PTX orally administered in poly(anhydride) NPs, combined with cyclodextrins and poly(ethylene glycol), displayed sustained plasma levels and significant antitumor effect in a syngenic tumor model of carcinoma in mice.

  8. Toxico-kinetics, recovery, and metabolism of napropamide in goats following a single high-dose oral administration.

    Science.gov (United States)

    Pahari, A K; Majumdar, S; Mandal, T K; Chakraborty, A K; Bhattacharyya, A; Chowdhury, A

    2001-04-01

    Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were studied following a single high-dose oral administration of 2.5 g kg(-1) and continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat. Napropamide was detected in blood at 15 min and the maximum quantity was recovered at 3 h after administration. The absorption rate constant (Ka) value was low indicating poor absorption from the gastrointestinal tract. High elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled with higher transfer of compound from tissue to central compartment (K(21)) suggest that napropamide persisted in the blood for a long time, i.e., after 72 h of oral administration. The recovery percentage of napropamide, including metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent compound through feces varied from 18.86 to 21.59%, indicating that a major portion of the orally administered napropamide was absorbed from the gastrointestinal tract of goat. Napropamide significantly increased the Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7--11.6%, respectively, during a 4--7 day period. The material balance of napropamide (including metabolites) following a single high-dose oral administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in the range of 75--80%.

  9. 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...... of sublingual tablets, the residence time of the model substance in the oral cavity was significantly longer than following administration of chewing gum. The residence time following administration of lozenges was found to be the shortest....

  10. Pharmacokinetics and residue depletion of erythromycin in gilthead sea bream Sparus aurata L. after oral administration.

    Science.gov (United States)

    Di Salvo, A; Pellegrino, R M; Cagnardi, P; della Rocca, G

    2014-09-01

    Erythromycin (ERY) is an antibiotic effective against Streptococcus iniae, a microorganism responsible for significant losses in aquaculture. No data are available on the pharmacokinetics and residue depletion of ERY in sea bream. The aim of this study was thus to evaluate the pharmacokinetics of ERY in this species after a single oral administration at 75 mg kg(-1) b.w. and to assess its residue depletion from tissues after prolonged treatment for 10 days. ERY was rapidly absorbed in sea bream (Cmax  = 10.04 μg g(-1) and Tmax =1 h), with a half-life of 9.35 h and an AUC0-24 of 56.81 (h μg mL(-1) ). The data obtained and the evaluation of pharmacokinetic/pharmacodynamic parameters allowed us to hypothesize that dosage used in this study should be effective against S. iniae. A rapid reduction in erythromycin concentrations was observed in tissues, with the drug being detectable only during the first day post-treatment. In Europe, the use of ERY in aquaculture is allowed by off-label prescription with a withdrawal time of 500 °C day(-1) . The absence of ERY residues in tissues already at 24 h post-treatment suggests that ERY in sea bream should not pose human food safety issues. © 2013 John Wiley & Sons Ltd.

  11. Effects of Oral Administration of Silymarin in a Juvenile Murine Model of Non-alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Veronica Marin

    2017-09-01

    Full Text Available The increasing prevalence of non-alcoholic fatty liver disease (NAFLD in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid profile, transaminases, HOMA-IR, steatosis, inflammation, fibrosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic life style changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a significant improvement in glycemia, visceral fat, lipid profile, and liver fibrosis. Moreover, it reduced (both in vitro and in vivo ALT, hepatic inflammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the beneficial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH.

  12. Oral administration of vitamin C and histidine attenuate cyclophosphamide-induced hemorrhagic cystitis in rats.

    Science.gov (United States)

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Ranjbar, Sepideh

    2013-01-01

    Cyclophosphamide (CP), a widely used antineoplastic drug causes hemorrhagic cystitis (HC) mainly via induction of oxidative stress. Both vitamin C and histidine have antioxidant properties. The present study aimed to investigate the effects of oral (p.o.) administration of vitamin C and histidine on the CP-induced HC in rats. The animals were divided into two major groups I and II with four subgroups (a, b, c, and d) in each. Groups I and II were treated with intraperitoneal (i.p.) injections of normal saline and CP (200 mg/kg), respectively, thereafter, normal saline, vitamin C (200 mg/kg), histidine (200 mg/kg) and vitamin C plus histidine were p.o. administered in subgroups a, b, c, and d, respectively, three times (2, 6, and 24 h) after i.p. injections of normal saline and CP. Blood samples were assayed for total antioxidant capacity (TAC) and malondialdehyde (MDA) levels. Histopathological changes of bladder wall were investigated. The decreased TAC and increased MDA levels of plasma and the severity of hemorrhages, congestion, edema, and leukocyte infiltration of bladder induced by CP were recovered with vitamin C and histidine treatments. Combined treatment with vitamin C and histidine showed a potentiation effect. The results indicated that vitamin C and histidine attenuated the CP-induced HC by reducing of free radical-induced toxic effects.

  13. Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.

    Science.gov (United States)

    Burke, Susan J; Batdorf, Heidi M; Eder, Adrianna E; Karlstad, Michael D; Burk, David H; Noland, Robert C; Floyd, Z Elizabeth; Collier, J Jason

    2017-03-01

    Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. [Oral administration of oil bleomycin combined with sodium polyacrylate for the treatment of esophageal cancer].

    Science.gov (United States)

    Kamano, T; Kishino, H; Mizukami, K; Azuma, N; Kondo, K; Watanabe, Y; Kidokoro, T

    1982-08-01

    With anticipation of potentiation of the regional effect of bleomycin on the lesion of esophageal carcinoma, 12 patients with esophageal carcinoma were medicated orally with 5 ml of a paste-like mixture of 1 g of Sodium polyacrylate (PANA Kayaku) and 30 mg of oil bleomycin every day for 7 to 43 preoperative days. These 12 patients were further medicated with the mixture 1 hour before operation, and in 9 of them, bleomycin levels in the tumor and normal tissue of the resected portion of the esophagus and also in the regional lymph nodes were determined. The level in the normal tissue was on average concentration of 1.2 micrograms/g, while the level in tumor showed a tendency to higher level, being an average concentration of an being 4.4 micrograms/g. Bleomycin was found being efficiently transferred into the regional lymph nodes, where it was detected the average concentration of 1.7 micrograms/g. It may be anticipated that this mixture will be effective against preoperative and inoperable esophageal carcinoma and for ther studies on dosage and administration schedule is desirable.

  15. 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

    2002-09-05

    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.

  16. The effects of oral magnesium hydroxide administration on rumen fluid in cattle.

    Science.gov (United States)

    Smith, Geoffrey W; Correa, Maria T

    2004-01-01

    This study was conducted to determine the effects of oral magnesium hydroxide administration on rumen fluid in cattle. Six lactating Holstein cows (4-7 years of age) with rumen fistulas were studied. Cattle were randomly assigned to receive boluses of magnesium hydroxide (162 g) or a powdered form (450 g dissolved in 3.5 L of water) PO daily for 3 days. Analysis of rumen fluid, blood gas tensions, and pH and measurement of serum magnesium concentrations were conducted daily. The study was discontinued after 72 hours, or sooner if rumen pH exceeded 8.0. After at least 3 weeks, the study was repeated with each cow receiving the other form of magnesium hydroxide (powder or bolus). Compared with baseline rumen pH (mean +/- SD: 6.22 +/- 0.28), magnesium hydroxide boluses caused a significant increase (P magnesium hydroxide decreased rumen protozoal numbers and increased methylene blue reduction times compared with baseline values. There was no change in blood pH, bicarbonate, or base excess values. Serum magnesium concentrations were significantly increased (P magnesium hydroxide powder. The results of this study indicate that magnesium hydroxide has a potent alkalinizing effect on rumen pH and significantly decreases rumen microbial activity.

  17. Urinary excretion of arbutin metabolites after oral administration of bearberry leaf extracts.

    Science.gov (United States)

    Quintus, Joachim; Kovar, Karl-Artur; Link, Peter; Hamacher, Harald

    2005-02-01

    An HPLC assay with fluorimetric detection of the arbutin metabolites hydroquinone glucuronide (2) and hydroquinone sulphate (6) in urine was developed and validated. Methylarbutin (4) and 6 were synthesised as reference substances. Compound 2 was prepared enzymatically from hydroquinone and uridine 5'-diphosphoglucuronic acid using the glucosyltransferase system of rat liver microsomes and enriched by two liquid-liquid and an additional solid phase extraction. Compound 2 as the main component of this purified product was identified by UV and fluorescence spectroscopy, by HPLC-MS, and by enzymatic hydrolysis to hydroquinone (5). The assay yields precise and accurate urine levels of 2, 5 and 6 in the concentration range expected after oral administration of recommended therapeutic doses of bearberry leaf extract. In a preliminary pharmacokinetic study on 3 volunteers the time-dependent renal excretion of arbutin metabolites 2, 5 and 6 was investigated after ingestion of an aqueous bearberry leaf extract containing an arbutin dose recommended by the German Kommission E. More than half of the administered dose of arbutin was excreted within 4 hours mainly in form of the metabolites 2 and 6 and more than 75 % of the total applied arbutin was excreted within 24 h. The elimination of 5 was negligible in 2 out of 3 volunteers. The excretion of this metabolite in the third test person reached 5.6 % of the total administered arbutin dose. The preliminary pharmacokinetic results confirm that renal elimination of toxicologically critical concentrations of the metabolite 5 will not be expected.

  18. Early effects of oral administration of lafutidine with mosapride compared with lafutidine alone on intragastric pH values

    Directory of Open Access Journals (Sweden)

    Koide Tomoko

    2009-07-01

    Full Text Available Abstract Background The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis and resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after a single oral administrations of lafutidine, is a newly synthesized H2-receptor antagonist, with mosapride 5 mg or lafutidine alone. Methods Ten Helicobacter pylori negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after a single oral administration of lafutidine 10 mg or lafutidine 10 mg with mosapride 5 mg (the lafutidine being administrated one hour after the mosapride. Each administration was separated by a 7-day washout period. Results The average pH during the 4-hour period after administration of lafutidine 10 mg with mosapride 5 mg was higher than after lafutidine 10 mg alone (median: 5.25 versus 4.58, respectively; p = 0.0318. During the 3–4 hour study period, lafutidine 10 mg with mosapride 5 mg provided a higher pH, compared to lafutidine 10 mg alone (median: 7.28 versus 6.42; p = 0.0208. Conclusion In H. pylori negative healthy male subjects, an oral dose of lafutidine 10 mg with mosapride 5 mg more rapidly increased intragastric pH than lafutidine 10 mg alone.

  19. 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.

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

    Science.gov (United States)

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

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

  1. 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

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

    Science.gov (United States)

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

    2010-09-01

    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. A systematic search of the literature was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. In oral surgery, most clinical trials showed a significant decrease in edema (P or =25 mg was expected to result in a significant decrease in edema. Regarding the analgesic effect, several clinical trials showed a decrease in pain after CS (P or =85 mg administered intravenously seemed sufficient to produce a significant decrease in edema, and several trials pointed toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis, and adrenal suppression was seen. There were no reports of decreased healing. These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Intestinal microbiota and oral administration of Enterococcus faecium associated with the growth performance of new-born piglets.

    Science.gov (United States)

    Wang, Y B; Du, W; Fu, A K; Zhang, X P; Huang, Y; Lee, K H; Yu, K; Li, W F; Li, Y L

    2016-09-01

    The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×10(8) cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (Pfaecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.

  4. 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. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Safety evaluation of lotilaner in dogs after oral administration as flavoured chewable tablets (Credelio™

    Directory of Open Access Journals (Sweden)

    Emmanuelle A. Kuntz

    2017-11-01

    Full Text Available Abstract Background Lotilaner (Credelio™, Elanco is a novel isoxazoline that provides rapid speed of flea and tick knockdown which is sustained for at least 1 month following oral administration to dogs. The safety of lotilaner flavoured chewable tablets was investigated in a randomized, blinded, parallel-group design study in healthy Beagle puppies starting at 8 weeks of age. Lotilaner was administered orally once a month over 8 months at one, three and five times the upper level of the recommended dose range (of 20 to 43 mg/kg. Methods The objective of this study was to determine the safety of lotilaner flavoured chewable tablets in healthy dogs when administered monthly over an extended time period at the highest recommended dose rate, i.e. 1× and at elevated dose rates, i.e. 3× and 5×. Sixteen male and 16 female healthy 8-week-old puppies, weighing ~1.5 to 3.0 kg, were randomized among four groups to be untreated controls or to receive lotilaner at dose rates of 43 mg/kg (1×, 129 mg/kg (3×, or 215 mg/kg (5× on eight occasions - every 4 weeks over 8 months. The control group was sham-dosed. Study dogs were fed within 30 min prior to treatment. Assessment of safety was based on general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations and clinical pathology evaluations (haematology, clinical chemistry and urinalysis, food and water consumption, body weight, pharmacokinetic blood collections, macroscopic and microscopic examinations. Results Blood concentrations of lotilaner confirmed systemic exposure of all study dogs with the exception of the control group. Lotilaner did not induce any treatment-related effects on body weight, food consumption, opthalmoscopic, physical/neurological and electrocardiographic examinations. For clinical pathology, no changes related to treatment were noted. There were no treatment-related changes in gross

  6. Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations.

    Science.gov (United States)

    Göhler, Karin; Brett, Martin; Smit, Johan W; Rengelshausen, Jens; Terlinden, Rolf

    2013-04-01

    To evaluate the bioavailability and pharmacokinetics of orally administered tapentadol immediate release (IR) compared with tapentadol prolonged release (PR). Three randomized, open-label, crossover studies were conducted in subjects under fasted conditions. Studies 1 and 2 determined the absolute bioavailability and pharmacokinetics of oral tapentadol IR 86 mg and tapentadol PR 86 mg, respectively, relative to a 34-mg intravenous (IV) dose of tapentadol. Study 3 determined the relative bioavailability of tapentadol PR 86 mg vs. tapentadol IR 86 mg. Pharmacokinetic parameters were calculated using non-compartmental analysis and relative bioavailability using dose-adjusted, log-transformed analysis of variance models for maximum concentration (Cmax) and areas under the serum concentration-time curve (AUC0-t and AUC). Adverse events (AEs), vital signs, 12-lead electrocardiograms (ECGs), and laboratory parameters were assessed. Absolute bioavailability was estimated to be 32% (95% confidence interval (CI), 29.4 - 34.8%; n = 24) for tapentadol IR 86 mg and 32% (95% CI, 28.0 - 35.9%; n = 18) for tapentadol PR 86 mg. Based on AUC, the relative bioavailability of tapentadol PR vs. tapentadol IR was 96% (90% CI, 87.8 - 104.4%; n = 16). Following IV administration, tapentadol had an elimination half-life of about 4 hours; in Studies 1 and 2, respectively, mean tapentadol volumes of distribution were 540 and 471 l, and mean clearance was 1,531 and 1,603 ml/min. Compared to tapentadol IR 86 mg, the prolonged-release characteristics of tapentadol PR 86 mg were evident with a lower Cmax (22.5 ng/ml vs. 64.2 ng/ml), a longer time to Cmax (5.0 h vs. 1.5 h), a higher half-value duration (HVD: 12.5 h vs. 3.6 h), and a longer mean residence time (MRT: 10.6 h vs. 6.0 h). The most common AEs reported were dizziness, headache, fatigue, nausea, somnolence, and dry mouth; most AEs were mild. No clinically relevant changes in vital signs, ECG parameters, or laboratory values were observed

  7. Pharmacokinetics of esomeprazole following intravenous and oral administration in healthy dogs

    Directory of Open Access Journals (Sweden)

    Cook EK

    2016-08-01

    Full Text Available Emily K Cook, Nana Satake, Ben W Sykes, Emma L Bennett, Paul C Mills School of Veterinary Sciences, The University of Queensland, Gatton, Queensland, Australia Abstract: Investigation into the pharmacokinetic profile of esomeprazole was conducted using eight healthy dogs after intravenous (IV and oral (po administration in a two-part randomized crossover study. The dogs were fasted for a minimum of 12 hours and then received esomeprazole either intravenously (dose range 0.93–1.48 mg/kg or orally using an enteric-coated formulation (dose range 0.95–1.50 mg/kg. After a 1-week washout period, the dogs received an alternative treatment. Serial blood samples were collected at predetermined time points, and plasma esomeprazole concentrations were determined by using ultra-high-performance liquid chromatography–mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Then, the area under the plasma concentration/time curve (AUC and maximal plasma concentration (Cmax values were normalized to a 1.0 mg/kg dose of esomeprazole, that is, AUC/dose. Median (range dose-normalized peak plasma concentration (Cmax values for the IV and po formulations were 4.06 µg/mL (2.47–4.57 µg/mL and 1.04 µg/mL (0.31–1.91 µg/mL, respectively. The median (range time-to-peak concentration (Tmax for the po formulation was 105 minutes (45–360 minutes. Median (range plasma terminal half-life (t½ was 45.56 minutes (39.43–64.20 minutes for the IV formulation and 63.97 minutes (44.02–109.94 minutes for the enteric-coated po formulation. The median (range po bioavailability was 63.33% (32.26%–79.77%. Clinically, both po and IV formulations were well tolerated with minimal side effects observed. Keywords: proton pump inhibitors, gastric ulcers, and oesophagitis

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

    Science.gov (United States)

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

    2010-04-01

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

  9. Plasma disposition of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in rabbits after oral administration.

    Science.gov (United States)

    Kim, Myoung-Seok; Lim, Jong-Hwan; Hwang, Youn-Hwan; Park, Byung-Kwon; Song, In-Bae; Yun, Hyo-In

    2010-04-19

    The objective of this study was to evaluate the pharmacokinetic profiles of toltrazuril (TZR), and its major metabolites toltrazuril sulfoxide (TZR x SO) and toltrazuril sulfone (TZR x SO(2)) in rabbits after oral administrations. Rabbits were dosed once with 10 and 20mg/kg TZR via stomach tube with manual restraint. The plasma concentrations of TZR, TZR x SO and TZR x SO(2) were determined by liquid chromatography/mass spectrometry. Plasma concentration-time data after single oral administration were analyzed by a non-compartmental analysis. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 30.2+/-1.5microg/mL at 20.0+/-6.9h, 8.9+/-1.3microg/mL at 20.0+/-6.9h and 14.7+/-3.9microg/mL at 96.0+/-0.0h after oral administration of TZR with 10mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 10mg/kg were 52.7+/-3.6, 56.1+/-10.7 and 76.7+/-7.5h, respectively. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 39.4+/-1.2microg/mL at 28.0+/-6.9h, 12.5+/-3.9microg/mL at 20.0+/-6.9h and 24.9+/-8.74microg/mL at 112.0+/-6.9h after oral administration of TZR with 20mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 20mg/kg were 56.7+/-1.9, 68.8+/-12.5 and 82.3+/-12.6h, respectively. In conclusion, TZR was very well-absorbed through the gastrointestinal tract and rapidly metabolized to TZR x SO and TZR x SO(2) in rabbits after oral administration. TZR x SO(2) was actually more slowly eliminated than TZR and TZR x SO.

  10. Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs.

    Science.gov (United States)

    Niyom, Sirirat; Mama, Khursheed R; De Rezende, Marlis L

    2012-04-01

    To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. Six 7- to 8-month-old dogs (3 males and 3 females). In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

  11. Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial. Diabète Insuline Orale group.

    Science.gov (United States)

    Chaillous, L; Lefèvre, H; Thivolet, C; Boitard, C; Lahlou, N; Atlan-Gepner, C; Bouhanick, B; Mogenet, A; Nicolino, M; Carel, J C; Lecomte, P; Maréchaud, R; Bougnères, P; Charbonnel, B; Saï, P

    2000-08-12

    Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes. We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy. Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat. Baseline C-peptide and haemoglobin A1c concentrations were similar in the three groups. During follow-up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A1c concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2. At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function.

  12. Treatment of infectious mastitis during lactation: antibiotics versus oral administration of Lactobacilli isolated from breast milk.

    Science.gov (United States)

    Arroyo, Rebeca; Martín, Virginia; Maldonado, Antonio; Jiménez, Esther; Fernández, Leónides; Rodríguez, Juan Miguel

    2010-06-15

    Mastitis is a common infectious disease during lactation, and the main etiological agents are staphylococci, streptococci, and/or corynebacteria. The efficacy of oral administration of Lactobacillus fermentum CECT5716 or Lactobacillus salivarius CECT5713, two lactobacilli strains isolated from breast milk, to treat lactational mastitis was evaluated and was compared with the efficacy of antibiotic therapy. In this study, 352 women with infectious mastitis were randomly assigned to 3 groups. Women in groups A (n = 124) and B (n = 127]) ingested daily 9 log(10) colony-forming units (CFU) of L. fermentum CECT5716 or L. salivarius CECT5713, respectively, for 3 weeks, whereas those in group C (n =101) received the antibiotic therapy prescribed in their respective primary care centers. Results. On day 0, the mean bacterial counts in milk samples of the 3 groups were similar (4.35-4.47 log(10) CFU/mL), and lactobacilli could not be detected. On day 21, the mean bacterial counts in the probiotic groups (2.61 and 2.33 log(10) CFU/mL) were lower than that of the control group (3.28 log(10) CFU/mL). L. fermentum CECT5716 and L. salivarius CECT5713 were isolated from the milk samples of women in the probiotic groups A and B, respectively. Women assigned to the probiotic groups improved more and had lower recurrence of mastitis than those assigned to the antibiotic group. Conclusions. The use of L. fermentum CECT5716 or L. salivarius CECT5713 appears to be an efficient alternative to the use of commonly prescribed antibiotics for the treatment of infectious mastitis during lactation. ClinicalTrials.gov identifier. NCT00716183.

  13. 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

  14. 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.

  15. Efficient Brain Uptake of Piperine and Its Pharmacokinetics Characterization after Oral Administration.

    Science.gov (United States)

    Ren, Tianjing; Wang, Qianwen; Li, Chenrui; Yang, Mengbi; Zuo, Zhong

    2017-11-21

    1. Piperine, the major biological active component in black pepper has been associated with miscellaneous pharmacological effects, especially on central nervous system. To correlates with its neurological activity, a comprehensive pharmacokinetic profile of piperine in brain, plasma and cerebrospinal fluid after oral administration in rats was investigated in the current study. 2. It was noted that piperine could efficiently penetrate and homogeneously distribute into brain with similar pharmacokinetics profiles in each region. In addition, piperine concentrations in brain and plasma were found to be comparable with brain to plasma AUC0→∞ ratios of 0.95 and 1.10 for total concentration and unbound concentrations, respectively. Piperine also demonstrated high affinity towards brain tissue (98.4-98.5%) and plasma protein (96.2-97.8%) leading to a brain distribution volume of 36.32±1.40 ml/g brain. Moreover, its efficient membrane permeability (Papp values of 5.41±0.40 × 10(-5) cm/sec and 4.78±0.16 × 10(-5) cm/sec for basolateral to apical and apical to basolateral transport in Caco-2 monolayer model) and limited hepatic metabolism (Clint of 8.15 μl/min/mg) could also contribute to its quick and high extent brain exposure. 3. In summary, the present study for the first time demonstrated high brain penetration potency of piperine could be resulted from its high brain tissue affinity and membrane permeability together with its limited liver metabolism.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

  18. Distribution and elimination of palladium in rats after 90-day oral administration.

    Science.gov (United States)

    Iavicoli, Ivo; Bocca, Beatrice; Fontana, Luca; Caimi, Stefano; Bergamaschi, Antonio; Alimonti, Alessandro

    2010-04-01

    This study determined the distribution in internal organs and the elimination routes in rats after oral administration of potassium hexachloro-palladate. Forty male Wistar rats were exposed for 90 days to 0, 10, 100 and 250 ng/mL of the palladium (Pd) salt in drinking water. Samples of urine and feces were collected on days 1, 30, 60 and 90, while organs (kidney, liver, lung, spleen and bones) and blood were collected at the end of the experiment. Quantification method was based on the sector-field inductively coupled plasma mass spectrometry. Results indicated that Pd ions were rapidly eliminated from the body. The principal excretion was through the feces (650 +/- 72.7 ng/g dry weight, at the Pd dose of 250 ng/mL), but at the higher dosing Pd was also eliminated through the urine (6.16 +/- 1.91 ng/mL for the Pd intake of 250 ng/mL). A clear relationship between the Pd ingested dose and the Pd excretion amount was observed mainly in the feces. Absorbed Pd was mostly found in the kidney of rats (124.4 +/- 23.0 ng/g dry weight, following the highest dose), while liver, lung, spleen and bones did not accumulate the metal. At the higher dosing, Pd content in the kidney raised proportionally with the Pd dose. Our findings may be useful to help in the understanding of the health impact of Pd dispersed in the environment as well as in identifying appropriate biological indices of Pd exposure.

  19. 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...

  20. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study.

    Science.gov (United States)

    Niezgoda, Piotr; Sikora, Joanna; Barańska, Malwina; Sikora, Adam; Buszko, Katarzyna; Siemińska, Emilia; Marszałł, Michał Piotr; Siller-Matula, Jolanta M; Jilma, Bernd; Alexopoulos, Dimitrios; Fabiszak, Tomasz; Kubica, Jacek

    2017-04-03

    Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.

  1. 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...

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

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Auchenberg, Michael

    2016-01-01

    Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max : 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were...... benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports........ 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 

  3. Antihypertensive Effect of Long-Term Oral Administration of Jellyfish (Rhopilema esculentum Collagen Peptides on Renovascular Hypertension

    Directory of Open Access Journals (Sweden)

    Yufeng Zhang

    2012-02-01

    Full Text Available 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 < 0.05, compared with model control group. However, the arterial blood pressure of normal rats showed no significant changes during long-term 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. Oral administration of Lactobacillus gasseri TMC0356 stimulates peritoneal macrophages and attenuates general symptoms caused by enteropathogenic Escherichia coli infection.

    Science.gov (United States)

    Yoda, Kazutoyo; He, Fang; Kawase, Manabu; Miyazawa, Kenji; Hiramatsu, Masaru

    2014-04-01

    Enteropathogenic Escherichia coli (EPEC) is an important cause of diarrhea in human. This study was conducted to investigate the ability of orally administrated probiotic lactobacilli to protect hosts from EPEC infection via enhancement of immune responses. Lyophilized Lactobacillus gasseri TMC0356 (TMC0356) was orally administered to Institute of Cancer Research (ICR) mice and Sprague Dawley (SD) rats for 11 and 7 days, respectively. These tested mice and rats were intraperitoneally injected with EPEC. Body weight, general symptoms (piloerection, soft stool, diarrhea, and anal hyperemia), and mortality of the tested mice were observed. Peritoneal macrophages were extracted from peritoneal cavity of tested rats, and their phagocytosis and cytokine production were analyzed. Oral administration of TMC0356 accelerated the disappearance of general symptoms and reduced mortality of EPEC-infected mice in the early phase. Peritoneal macrophages from rats orally administered with TMC0356 showed significant increases in phagocytic activity (p < 0.05) and interleukin (IL)-6 production (p < 0.01) compared to those from control rats. Tumor necrosis factor-α and production of IL-1β, IL-10, and IL-12 slightly increased, although the changes were not statistically significant. These results suggest that some of selected probiotic lactobacilli may, at least partly, protect hosts from EPEC infection by the enhancement of innate immunity of host and attenuate symptoms caused by the infection. Copyright © 2012. Published by Elsevier B.V.

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

    OpenAIRE

    Hecq, Julien

    2017-01-01

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

  6. 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.

  7. Pharmacokinetics of famciclovir and penciclovir in tears following oral administration of famciclovir to cats: a pilot study.

    Science.gov (United States)

    Thomasy, Sara M; Covert, Jill C; Stanley, Scott D; Maggs, David J

    2012-09-01

    To validate a means of collecting tears from cats, develop an assay for quantifying famciclovir and penciclovir in tears, and to assess famciclovir and penciclovir concentrations and pharmacokinetics in the tears of cats being treated orally with famciclovir for suspected herpetic disease. Seven client-owned cats. Cats were treated orally with a median (range) dose of 40 (39-72) mg of famciclovir/kg three times daily for at least 24 h. At various time points following famciclovir administration, tear samples were collected using Schirmer tear test strips. Tear famciclovir and penciclovir concentrations were measured using liquid chromatography-mass spectrometry, and concentration-time profiles were analyzed noncompartmentally. The relationship between famciclovir dose and tear penciclovir concentration near its maximum was evaluated using least squares linear regression. Maximum tear famciclovir concentration of 0.305 μg/mL occurred at 2.64 h; elimination half-life was 2.28 h. Maximum tear penciclovir concentration (0.981 μg/mL) occurred 2.25 h following oral administration of famciclovir; elimination half-life was 2.77 h. A significant positive correlation was noted between famciclovir dose and tear penciclovir concentration at various time points between 0.5 and 3.75 h following drug administration (P = 0.025). Tear penciclovir concentration exceeded the concentration shown to have in vitro efficacy against feline herpesvirus (FHV-1) (0.304 μg/mL) in about half of samples collected. Oral administration of 40 mg of famciclovir/kg to cats resulted in a tear penciclovir concentration-time profile that approximated the plasma penciclovir concentration-time profile and frequently achieved a penciclovir concentration at the ocular surface likely to be effective against FHV-1. © 2012 American College of Veterinary Ophthalmologists.

  8. Design of Lipid-Based Formulations for Oral Administration of Poorly Water-Soluble Drug Fenofibrate: Effects of Digestion

    OpenAIRE

    Mohsin, Kazi

    2012-01-01

    Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV self-emulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, no...

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

    OpenAIRE

    Farhadi, Naser; Gharghani, Majid; Farhadi, Zahra

    2016-01-01

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

  10. Oral Administration of Herbal Mixture Extract Inhibits 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Soon Re Kim

    2014-01-01

    Full Text Available CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB- induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL- 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1. In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.

  11. Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice.

    Science.gov (United States)

    Kim, Soon Re; Choi, Han-Seok; Seo, Hye Sook; Ku, Jin Mo; Hong, Se Hyang; Yoo, Hye Hyun; Shin, Yong Cheol; Ko, Seong-Gyu

    2014-01-01

    CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.

  12. 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.

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

    Science.gov (United States)

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

    2010-02-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

    Directory of Open Access Journals (Sweden)

    Shu-Ting Chan

    2014-01-01

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

  16. Administration

    OpenAIRE

    2009-01-01

    Cet imposant volume constitue un registre des cours magistraux tenus par l’auteur à l’École supérieure allemande des sciences administratives de Spire, enrichis des résultats de travaux scientifiques menés principalement à l'Institut Allemand de Recherche en Administration Publique (Deutsches Forschungsinstitut für öffentliche Verwaltung Speyer, FÖV). Il s’agit donc d’une entreprise au long cours, destinée à apporter un nouvel éclairage (quasi ?) exhaustif sur l’administration publique : son ...

  17. Bioequivalence study between two formulations of ciclosporin A (Cyclavance® oral solution and Atopica® soft capsules) following a single oral administration to dogs.

    Science.gov (United States)

    Navarro, C; Séguy, L; Vila, M; Birckel, P

    2016-03-12

    Ciclosporin is a selective immunomodulator used for the treatment of atopic dermatitis in dogs. A new 100 mg/ml oral solution formulation (Cyclavance®, Virbac) was developed as a pharmaceutical equivalent to the marketed capsule formulations (Atopica®, Novartis Animal Health) containing 25, 50 mg, or 100 mg of ciclosporin A. The aim of this study was to assess and compare the pharmacokinetic profiles and bioequivalence of the two formulations following a single oral administration to dogs. This randomised, two-period, two-sequence, crossover bioequivalence study was conducted in 40 healthy dogs under fasting conditions. Each dog received either one 50 mg capsule of Atopica® or 0.5 ml of Cyclavance®. After dosing, blood samples were collected during a 48-h time period at 0, 0.5, 1, 2, 4, 6, 12, 24, 36 and 48 h. Blood ciclosporin A concentrations were measured by using an HPLC-MS/MS method. Cmax, Tmax, t1/2, AUC0-t, AUC0-∞ and Kel were determined for the two ciclosporin formulations. Bioequivalence was to be concluded if the 90% confidence intervals were within the range of 80% to 125% for Cmax and AUC0-t. Dogs were monitored once daily throughout the study period for adverse effects. The 90% confidence intervals for Cyclavance®/Atopica® mean ratios of the log-transformed pharmacokinetic variables Cmax and AUC0-t were within the conventional bioequivalence range of 80% to 125% (Point estimate: 101.2% and 101.4% respectively). Except for salivation reported after administration of both products, or vomiting and diarrhoea reported after Atopica® administration, both formulations were well tolerated in the 40 healthy dogs over the 48-h study period. The two ciclosporin oral formulations demonstrated similar pharmacokinetic profiles and were found to be bioequivalent, and therefore, interchangeable.

  18. 29 CFR 1915.1008 - bis-Chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false bis-Chloromethyl ether. 1915.1008 Section 1915.1008 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1008 bis-Chloromethyl ether. Note: The requirements applicable to shipyard employment under this...

  19. 29 CFR 1915.1006 - Methyl chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1915.1006 Section 1915.1006 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1006 Methyl chloromethyl ether. Note: The requirements applicable to shipyard...

  20. 29 CFR 1926.1108 - bis-Chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false bis-Chloromethyl ether. 1926.1108 Section 1926.1108 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...-Chloromethyl ether. Note: The requirements applicable to construction work under this section are identical to...

  1. 29 CFR 1910.1008 - bis-Chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 6 2010-07-01 2010-07-01 false bis-Chloromethyl ether. 1910.1008 Section 1910.1008 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... bis-Chloromethyl ether. See § 1910.1003, 13 carcinogens. ...

  2. 29 CFR 1910.1006 - Methyl chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 6 2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1910.1006 Section 1910.1006 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Substances § 1910.1006 Methyl chloromethyl ether. See § 1910.1003, 13 carcinogens. ...

  3. 29 CFR 1926.1106 - Methyl chloromethyl ether.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Methyl chloromethyl ether. 1926.1106 Section 1926.1106 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1106 Methyl chloromethyl ether. Note: The requirements applicable to construction work under this...

  4. 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.

  5. Developmental toxicity of N-methylaniline following prenatal oral administration in rats

    Directory of Open Access Journals (Sweden)

    Krystyna Sitarek

    2016-06-01

    Full Text Available Objectives: The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA administered by gavage to pregnant female rats. Material and Methods: Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w., 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating to the day prior to the scheduled caesarean section (the 20th day of pregnancy. General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results: All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3 and free triiodothyronine (FT4 thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions: Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL for the progeny.

  6. 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.

  7. Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations

    NARCIS (Netherlands)

    Gohler, K.; Brett, M.; Smit, J.W.A.; Rengelshausen, J.; Terlinden, R.

    2013-01-01

    OBJECTIVE: To evaluate the bioavailability and pharmacokinetics of orally administered tapentadol immediate release (IR) compared with tapentadol prolonged release (PR). METHODS: Three randomized, open-label, crossover studies were conducted in subjects under fasted conditions. Studies 1 and 2

  8. Tissue distribution of amiodarone and desethylamiodarone in rats after repeated oral administration of various amiodarone dosages

    NARCIS (Netherlands)

    Plomp, T. A.; Wiersinga, W. M.; Maes, R. A.

    1985-01-01

    Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was investigated after repeated oral application of various dosages of the drug. Serum and tissue concentrations ofBamiodarone and desethylamiodarone were assessed by high-performance liquid chromatography. The

  9. Pharmacokinetics, metabolism and excretion of [14C]-lenalidomide following oral administration in healthy male subjects

    OpenAIRE

    Chen, Nianhang; Wen, Lian; Lau, Henry; Surapaneni, Sekhar; Kumar, Gondi

    2011-01-01

    Purpose Assessment of the absorption, metabolism and excretion of [14C]-lenalidomide in healthy male subjects following a single oral dose. Methods Six healthy male subjects were administered a single 25 mg oral suspension dose of [14C]-lenalidomide. Blood (plasma), semen and excreta were collected. Mass balance assessments were done by radioactivity measurements. Metabolite profiling and quantitation were accomplished using liquid chromatography with mass spectrometric and radiochemical dete...

  10. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration

    OpenAIRE

    Hoffmann, Matthew; Kasserra, Claudia; Reyes, Josephine; Schafer, Peter; Kosek, Jolanta; Capone, Lori; Parton, Anastasia; Kim-Kang, Heasook; Surapaneni, Sekhar; Kumar, Gondi

    2012-01-01

    Purpose To investigate the pharmacokinetics and disposition of [14C]pomalidomide following a single oral dose to healthy male subjects. Methods Eight subjects were administered a single 2?mg oral suspension of [14C]pomalidomide. Blood (plasma), urine and feces were collected. Mass balance of radioactivity and the pharmacokinetics of radioactivity, pomalidomide and metabolites were determined. Metabolite profiling and characterization was performed. The enzymes involved in pomalidomide metabol...

  11. Comparison of the efficacy and adverse effects of sustained-release buprenorphine hydrochloride following subcutaneous administration and buprenorphine hydrochloride following oral transmucosal administration in cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Catbagan, Davina L; Quimby, Jessica M; Mama, Khursheed R; Rychel, Jessica K; Mich, Patrice M

    2011-04-01

    To compare the efficacy and adverse effects of sustained-release (SR) buprenorphine following SC administration and buprenorphine following oral transmucosal (OTM) administration in cats undergoing ovariohysterectomy. Animals-21 young healthy female cats. As part of anesthetic premedication (0 hours), 10 cats received buprenorphine (0.02 mg/kg) via OTM administration with additional doses at 12, 24, 36, 48, and 60 hours and 11 cats received an equivalent total dose as a single SC injection of SR buprenorphine (0.12 mg/kg). The SR product contained buprenorphine hydrochloride in a proprietary SR matrix. All other anesthetic drugs and a single postoperative dose of meloxicam were administered similarly to all cats. Behavioral and physiologic variables were recorded, and signs of pain were assessed by use of 2 pain assessment scales and von Frey filament testing in each cat prior to premedication administration (baseline), during recovery from anesthesia (RFA), and at 12, 24, 36, 48, 60, and 72 hours. Heart rate increased and temperature (determined via microchip transponder thermometry) decreased from baseline values during RFA in both groups. Compared with baseline values, pain scores were increased during RFA and at the 12- and 24-hour time points in both groups; von Frey scores were higher during RFA. Behavioral and physiologic variables did not differ significantly between groups at any time point. In cats undergoing ovariohysterectomy, SC administration of a preoperative dose of SR buprenorphine appeared to have comparable efficacy and adverse effect profile as that of twice-daily OTM administration of buprenorphine before and after surgery.

  12. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.

    Science.gov (United States)

    Choi, S-P; Oh, H-N; Choi, C-Y; Ahn, H; Yun, H S; Chung, Y M; Kim, B; Lee, S J; Chun, T

    2018-03-01

    In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model. © 2017 The Society for Applied Microbiology.

  13. 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.

  14. Preparation and Characterization of Sulfonated Poly (ether ether ...

    African Journals Online (AJOL)

    Proton-conducting membranes of organic–inorganic (sulfonated poly (ether ether ketone)/phosphated zirconia nanoparticles) composite were prepared by incorporating various ratios of phosphated zirconia nanoparticles (ZP) in sulfonated poly (ether ether ketone) (SPEEK). SPEEK/ZP showed an improvement of ...

  15. Ether formulations of relativity

    Energy Technology Data Exchange (ETDEWEB)

    Duffy, M.C.

    1980-12-01

    Contemporary ether theories are surveyed and criticized, especially those formally identical to orthodox Relativity. The historical development of Relativity, Special and General, in terms of an ether, is briefly indicated. Classical interpretations of Generalized Relativity using ether are compared to Euclidean formulations using a background space. The history of a sub-group of theories, formulating a 'new' Relativity involving modified transforms, is outlined. According to the theory with which they agree, recent supposed detections of drift are classified and criticized. Cosmological evidence suggesting an ether is mentioned. Only ether theories formally identical to Relativity have been published in depth. They stand criticized as being contrary to the positivist spirit. The history of mechanical analogues is traced, from Hartley's representing gravitating matter as spherical standing waves, to recent suggestions that vortex-sponge might model electromagnetic, quantum, uncertainty and faster-than-light phenomena. Contemporary theories are particular physical theories, themselves 'second interpretations' of a primary mathematical model. Mechanical analogues are auxiliary, not necessary, to other theory, disclosing relationships between classical and non-classical descriptions of assemblies charging state. The ether-relativity polemic, part of a broader dispute about relativity, is founded on mistaken conceptions of the roles of mathematical and physical models, mechanical analogues; and a distored view of history, which indicates that ether theories have become relativistic. 103 references.

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

    Directory of Open Access Journals (Sweden)

    Wenhui Wu

    2012-03-01

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

  17. 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.

  18. Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

    Directory of Open Access Journals (Sweden)

    Osamu Shido

    2013-05-01

    Full Text Available Natural killer (NK cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA and eicosapentaenoic (EPA acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day or DHA (240 mg/kg BW/day were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.

  19. Hypersensitivity Reaction Following Administration of Low-Dose Oral Vancomycin for the Treatment of Clostridium difficile in a Patient With Normal Renal Function.

    Science.gov (United States)

    Baumgartner, Laura J; Brown, Lauren; Geier, Curt

    2017-12-01

    Systemic absorption of oral vancomycin for the treatment of Clostridium difficile is thought to be trivial in patients without risk factors for increased systemic absorption and is often overlooked in clinical practice. A 51-year-old male elicits a suspected immunoglobulin E-mediated hypersensitivity following administration of low-dose oral vancomycin for the treatment of severe C difficile. The patient had normal renal function and was administered low doses of the medication, however, had a medical history significant for diverticulitis. Applying the Naranjo adverse drug reaction probability scale, a score of 5 was obtained, indicating a probable association between the administration of oral vancomycin and the hypersensitivity reaction. This case demonstrates that hypersensitivity reactions following low-dose oral vancomycin administration in patients with severe C difficile are possible, despite having normal renal function. Other risk factors for systemic absorption of oral vancomycin need to be evaluated in the literature, including severity of disease and underlying gastrointestinal processes.

  20. 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

  1. 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. British Veterinary Association.

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

    Directory of Open Access Journals (Sweden)

    Shigeru Nakamura

    2017-04-01

    Full Text Available Sea buckthorn (Hippophae rhamnoides–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1, a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

  3. Nanostructured lipid (NLCs) carriers as a bioavailability enhancement tool for oral administration.

    Science.gov (United States)

    Gaba, Bharti; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Sahni, Jasjeet K; Ali, Javed

    2015-01-01

    Nanostructured lipid carrier (NLCs) is the second generation solid lipid nanoparticles (NPs) made up of physiological, biocompatible, biodegradable, non-sensitizing and non-irritating lipids. The main objective of this review is to explore the role of NLCs system for delivering drugs by oral route and thus increasing the oral bioavailability. The present review article highlights the definition and types of NLCs and their importance as colloidal carriers including the production techniques and their formulation. This review article also deals with the fate of lipids used in the NLCs formulation and the NLCs toxicity. On the basis of the literature survey done, it was concluded that the NLCs enhances the oral bioavailability of the drug and may decrease the side effects and toxicity of the lipids used in other polymeric NPs as NLCs uses physiological and biodegradable lipids.

  4. Whole-Body Distribution of Donepezil as an Acetylcholinesterase Inhibitor after Oral Administration in Normal Human Subjects: A 11C-donepezil PET Study

    National Research Council Canada - National Science Library

    Ikuko Mochida; Eku Shimosegawa; Yasukazu Kanai; Sadahiro Naka; Jun Hatazawa; Keiko Matsunaga; Kayako Isohashi; Genki Horitsugi; Tadashi Watabe; Hiroki Kato

    2017-01-01

    .... Therefore, we aimed to examine the whole-body distribution of donepezil (DNP) as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP.Methods...

  5. 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.

  6. oral

    African Journals Online (AJOL)

    association between oral candidosis and. AIDS; the first documented patient with. AIDS had oral candidosis.3 A sub- stantial amount of data now emphasise its high prevalence in HIV-infected individuals. The manifestations of candidal infection in HIV-infected persons are restricted to superficial mucosal lesions of varying ...

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

    Science.gov (United States)

    Erbas, Mesut; Simsek, Tuncer; Kiraz, Hasan Ali; Sahin, Hasan; Toman, Huseyin

    2015-01-01

    Tenoxicam is widely used in osteoarthritis treatment and we aimed to compare the effectivity of oral and intra-articular administration of tenoxicam in osteoarthritis treatment. This study was performed between 2011 and 2012 by retrospectively analyzing and comparing the findings of 60 patients who were clinically and radiologically diagnosed with knee degenerative osteoarthritis in Bünyan state hospital pain policlinic. 60 patients included in the study were divided into two groups. The first group (tenoxicam IA, n=30) included patient findings of those subjected to intra-articular injection of 20mg tenoxicam to the knee once a week for three weeks and the second group (oral tenoxicam, n=30) included patients who were administered 20mg oral tenoxicam once a day for three weeks. All patients were clinically evaluated pre-treatment and in the 1st week, 1st month and 3rd month post-treatment according to specified criteria. Twenty two of 60 patients included in the study were male and 38 were female. In both groups significant improvements were detected in all of the observed parameters: visual analog scale, Western Ontario McMaster Osteoarthritis Index (pain, physical activity, 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 compliance to treatment and gastrointestinal system tolerability in tenoxicam IA group was also observed. Intra-articular tenoxicam administration could be thought as an alternative treatment method in patients with knee osteoarthritis who cannot use oral tenoxicam especially due to systemic gastrointestinal system side effects and those who have difficulties in adapting to treatment. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

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

    Science.gov (United States)

    Erbas, Mesut; Simsek, Tuncer; Kiraz, Hasan Ali; Sahin, Hasan; Toman, Huseyin

    2015-01-01

    Tenoxicam is widely used in osteoarthritis treatment and we aimed to compare the effectivity of oral and intra-articular administration of tenoxicam in osteoarthritis treatment. This study was performed between 2011 and 2012 by retrospectively analyzing and comparing the findings of 60 patients who were clinically and radiologically diagnosed with knee degenerative osteoarthritis in Bünyan state hospital pain policlinic. 60 patients included in the study were divided into two groups. The first group (tenoxicam IA, n=30) included patient findings of those subjected to intra-articular injection of 20mg tenoxicam to the knee once a week for three weeks and the second group (oral tenoxicam, n=30) included patients who were administered 20mg oral tenoxicam once a day for three weeks. All patients were clinically evaluated pre-treatment and in the 1st week, 1st month and 3rd month post-treatment according to specified criteria. 22 of 60 patients included in the study were male and 38 were female. In both groups significant improvements were detected in all of the observed parameters: visual analog scale, Western Ontario McMaster Osteoarthritis Index (pain, physical activity, 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 compliance to treatment and gastrointestinal system tolerability in tenoxicam IA group was also observed. Intra-articular tenoxicam administration could be thought as an alternative treatment method in patients with knee osteoarthritis who cannot use oral tenoxicam especially due to systemic gastrointestinal system side effects and those who have difficulties in adapting to treatment. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  9. 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.

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

    Science.gov (United States)

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

    1975-06-01

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

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

    OpenAIRE

    Juan Manuel Carballeda; Silvina Chimeno Zoth; Evangelina Gómez; María Soledad Lucero; María José Gravisaco; Analía Berinstein

    2015-01-01

    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.

  12. 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.

  13. Pharmacokinetics of pidotimod in broiler chickens by UHPLC-MS/MS after oral and intravenous administration.

    Science.gov (United States)

    Zhang, Ruili; Qiu, Mei; Zhao, Li; Cui, Liangliang; Wang, Chunyuan; Zhu, Jiajia; Hao, Zhihui

    2018-03-01

    Pidotimod is widely used in children as an immune promoter but it has not been fully evaluated in animals. The pharmacokinetics of pidotimod and its oral bioavailability have not been described in broiler chickens. We developed a simple and sensitive UHPLC-MS/MS assay for rapid determination of pidotimod levels in chicken blood. Recoveries were nearly 100% and the coefficients of accuracy and precision were minimal. Healthy broiler chickens were given 10 mg/kg pidotimod either orally or intravenously. The oral pidotimod was rapidly absorbed (time to reach maximum concentration, 1.25 h) and rapidly eliminated (the mean residence time was 3.2 h). A noncompartmental analysis of the intravenous route indicated a mean plasma clearance of 2.2 L (h kg) -1 with an estimated mean volume of distribution at steady state of 12.69 L/kg. The bioavailability of pidotimod after oral dosing was 27%. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Acute oral administration of lauric acid reduces energy intake in healthy male

    DEFF Research Database (Denmark)

    Feltrin, K. L.; Brennan, I.M.; Rades, Thomas

    2014-01-01

    Background and aims We have established that acute intraduodenal infusion of the fatty acid, lauric acid (“C12”), markedly reduces energy intake in healthy subjects in the absence of adverse effects. The aim of this study was to investigate the hypothesis that increasing doses of orally ingested C...

  15. Effects of Oral Administration of the Latex of Calotropis procera on ...

    African Journals Online (AJOL)

    Keyword: Blood chemistry, Calotropis procera, HB, PCV, rat, weight. The latex of Calotropis procera was obtained daily and administered to groups of rats through oral cannular in different sets of study. In one set of study, the latex was administered daily at varying doses and the packed cell volume (PCV), red blood cell ...

  16. Spatial trends of polybrominated diphenyl ether (PBDE) congeners

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Spatial trends of polybrominated diphenyl ether (PBDE) congeners were analyzed in young of the year bluefish collected along the U.S. Atlantic coastline from...

  17. Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats.

    Science.gov (United States)

    Zhang, Jun; Li, Chang-Yin; Xu, Mei-juan; Wu, Ting; Chu, Ji-Hong; Liu, Shi-Jia; Ju, Wen-Zheng

    2012-10-31

    Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and antitumor effects, celastrol has been considered as a promising candidate for drug development. To establish a sensitive LC-MS/MS method to investigate the pharmacokinetic properties of celastrol in rats. Key pharmacokinetic issues of celastrol including oral bioavailability, comparative pharmacokinetics between pure compound and tablet preparation, as well as gender-related pharmacokinetic difference are to be addressed for the first time. Sprague-Dawley rats were administrated an intravenous dose (100 μg kg(-1)) of pure celastrol and an oral dose (1000 μg kg(-1)) of pure celastrol and TGV tablets (corresponding to 534 μg kg(-1) of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC-MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration-time curve (AUC), maximal plasma concentration (Cmax), the time for maximal concentration (Tmax) and mean residence time (MRT) were estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese Pharmacological Association, Anhui, PR China). Statistical analysis was performed using two one-side t test with p-values less than 0.05 as the level of significance. The standard curve of celastrol showed good linearity in the concentration range of 0.11~54.3 ng mL(-1) in our current method, with acceptable selectivity, precision, recovery, and stability. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41) μg L(-1) and (379.49±118.19) μg h L(-1), which were significantly higher (pTGV tablets orally administered, and thereby

  18. Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration

    Science.gov (United States)

    2014-01-01

    Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

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

    Energy Technology Data Exchange (ETDEWEB)

    Kropp, J. [Dept. of Nuclear Medicine, Technical Univ. of Dresden (Germany); Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Lab., TN (United States); Weyenberg, A. [Dept. of Nuclear Medicine, Univ. of Bonn (Germany); McPherson, D.W. [Nuclear Medicine Group, Oak Ridge National Lab., TN (United States); Ambrose, K.R. [Nuclear Medicine Group, Oak Ridge National Lab., TN (United States); Callahan, A.P. [Nuclear Medicine Group, Oak Ridge National Lab., TN (United States); Bergmann, K. von [Dept. of Internal Medicine, Univ. of Bonn (Germany); Biersack, H.J. [Dept. of Nuclear Medicine, Univ. of Bonn (Germany)

    1994-11-01

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

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

    Science.gov (United States)

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

    2008-12-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  2. Changes in hepatic gene expression upon oral administration of taurine-conjugated ursodeoxycholic acid in ob/ob mice.

    Directory of Open Access Journals (Sweden)

    Jae-Seong Yang

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05, whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis.

  3. 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...

  4. 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.

  5. Androgens and oestrogens before and following oral testosterone administration in male patients with and without alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Dejgaard, A; Bennett, Patrick

    1987-01-01

    testosterone, serum concentrations of testosterone, dihydrotestosterone, androstenedione, and oestrone increased significantly (P less than 0.05) in both groups, cirrhotic patients reaching significantly (P less than 0.01) higher concentrations than controls. Further, in the cirrhotic group, the serum...... concentrations of oestrone sulphate, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol, and the urinary excretion of oestrogen increased significantly P less than 0.05). In conclusion, peroral testosterone administration decreases the serum oestradiol/testosterone ratio in patients...... than 0.05) lower concentrations of albumin and non-SHBG bound testosterone; no significant differences regarding concentrations of testosterone, dihydrotestosterone, non-protein bound testosterone, oestrone sulphate, and SHBG bound oestradiol. Following oral administration of 400 mg of micronized...

  6. Oral Administration of N-Acetyl-D Glucosamine Polymer Particles Down-Regulates Airway Allergic Responses

    National Research Council Canada - National Science Library

    Shibata, Yoshimi

    2006-01-01

    ... (IL-12, IL-18 and TNFo) that down-regulate allergic immune responses. We also found that administration of chitin particles resulted in less likely induce the production of IL-10 and prostaglandin E2 (PGE2...

  7. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review

    OpenAIRE

    Batchelor, Hannah K.

    2015-01-01

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulat...

  8. Bioelement status with oral administration of fish oil methyl ester and diesel fuel in male rats.

    Science.gov (United States)

    Aksoy, Laçine; Tütüncü, Hakan; Alper, Yasemin; Büyükben, Ahmet

    2012-10-01

    This paper is a study on the effects on the amounts of trace elements in case of possible repeat accidental or environmental exposure with fish oil biodiesel. For this purpose, 35 male Wistar albino rats were used in the study. Rats were divided into five groups. The first group was determined as the control group. The rats in this group were gavaged orally with 250 mg/kg sunflower oil. The rats in the second and third groups were administered by oral gavage of 250 mg/kg (D1) and 500 mg/kg (D2) diesel fuel mixed with equal amounts of sunflower oil, respectively. The rats in the fourth group were administered by oral gavage of 250 mg/kg fish oil biodiesel (F1) and the rats in the fifth group were administered by oral gavage of 500 mg/kg fish oil biodiesel (F2), both mixed with equal amounts of sunflower oil. At the end of the study, bioelement concentrations in the serum and the kidney, lung, and liver tissues were measured using inductively coupled plasma-optical emission spectroscopy. It was observed that serum Ca, Mg, and Sr concentrations were significantly (pbioelements concentrations were lower in diesel and biodiesel groups than in control group. Due to consumption for biochemical reaction of these elements, bioelements concentration could be low in diesel and biodiesel groups. Some trace elements concentrations in the kidney and liver were very high in the diesel groups. High concentration of these elements in the diesel groups might cause toxic effects. Fish oil biodiesel could be chosen as an alternative fuel instead of diesel fuel.

  9. Tolerance of, and metabolic effects of, preoperative oral carbohydrate administration in children - a preliminary report.

    Science.gov (United States)

    Gawecka, Agnieszka; Mierzewska-Schmidt, Magdalena

    2014-01-01

    The need for long preoperative fasting has been questioned. Recent data shows that intake of an oral carbohydrate-containing clear fluid prior to anaesthesia is safe and may have a positive impact on recovery and metabolic status and could improve glucose tolerance. Such solutions are routinely used in adults but not children. The aim of this study was to evaluate the safety, tolerance and influence of oral carbohydrate on selected metabolic parameters in children. With ethics committee approval and parental informed consent, 20 children, aged 4-17 years, ASA status I or II, scheduled for abdominal or thoracic surgery were randomised either to Group 1 - receiving a 12.6% carbohydrate-containing drink (10 mL kg(-1) the evening before surgery and two hours before anaesthesia), or the control Group 2 - fasting. Serum glucose and insulin concentration were measured four times: before and after anaesthesia, in the evening after surgery, and the following morning. IGF-1 concentration was measured once, before surgery. Insulin resistance was assessed by the HOMA-IR equation. Oral carbohydrate solution was well tolerated and no adverse events were noted. Glucose concentrations were within the normal range in both groups. Insulin concentration did not show significant differences between groups, however before surgery it tended to be lower in Group 1. Insulin resistance after surgery was significantly higher in Group 2 (2.0 vs. 0.62, P = 0.03), also the increase in insulin resistance after operation was significant only in the control group (P = 0.03). Oral carbohydrates are safe, well tolerated and do not cause any perioperative adverse events. They seem to improve postoperative metabolism by decreasing insulin resistance.

  10. Formulation, development and validation of insulin loaded particulate systems for their oral administration

    OpenAIRE

    Diop, Mouhamadou

    2015-01-01

    Insulinotherapy helps diabetics to regulate their glycaemia. This thesis is part of the ORAIL Bis project which aims to develop an oral insulin delivery system based on the double encapsulation of insulin. The developed vector is composed of a capsule containing insulin loaded particles (NPs) formulated with chitosan (CS) by complex coacervation or poly (lactic-co-glycolic) acid (PLGA) by double emulsion solvent evaporation. The objectives of the thesis are to stabilize chitosan NPs by crossl...

  11. Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration.

    Science.gov (United States)

    Freeman, Kate S; Thomasy, Sara M; Stanley, Scott D; Van Bonn, William; Gulland, Frances; Friedlaender, Ari S; Maggs, David J

    2013-10-15

    To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris). Pharmacokinetic study. 18 juvenile northern elephant seals without signs of ocular disease. Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis. Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 μg/mL at 6.1 hours on day 1 and was 1.5 μg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 μg/mL at 2.3 hours on day 1 and 1.9 μg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing. Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species.

  12. The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

    Science.gov (United States)

    Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2017-02-01

    Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

  13. Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

    Science.gov (United States)

    Monk, Caroline S; Sweeney, Raymond W; Bernstein, Lawrence R; Fecteau, Marie-Eve

    2016-02-01

    To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. 8 healthy neonatal calves. Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

  14. Benefits of oral administration of an electrolyte solution interrupting a prolonged preoperatory fasting period in pediatric patients.

    Science.gov (United States)

    Moyao-García, D; Corrales-Fernández, M A; Blanco-Rodríguez, G; Sánchez-Hernández, E; Nava-Ocampo, A A

    2001-03-01

    The aim of this study was to evaluate the benefits of an oral isosmolar solution of electrolytes (ISE) administered to interrupt a prolonged fasting period in children undergoing an elective surgical procedure under general anesthesia. Forty unpremedicated children aged 3 to 12 years, ASA I, undergoing a surgical procedure requiring general anesthesia were assigned randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight fasting period for milk and solids of at least 8 hours. In group 2, patients under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3 hours before completing the fasting period. After anesthetic induction, blood glucose level (BGL) was quantified, and patients underwent an endoscopic examination to obtain the gastric content to determine the residual gastric volume (RGV) and pH levels. In group 1, the RGV was 0.78 +/- 0.44 mL/kg, pH was 1.75 +/- 0.38, and BGL was 86.4 +/- 14.5. In group 2, the RGV was 0.40 +/- 0.29 mL/kg, pH was 3.18 +/- 0.61, and BGL was 85.1 +/- 12.6. Only RGV and pH were significantly different between groups. A prolonged fasting period interrupted with oral ISE administration resulted in an RGV of low risk, without counterbalancing a potential fasting-induced hypoglycemia.

  15. Influence of B-Complex Vitamins on the Pharmacokinetics of Ginsenosides Rg1, Rb1, and Ro After Oral Administration.

    Science.gov (United States)

    Zheng, Peihe; Chen, Yinbin; Fu, Yangyang; Wang, Hecheng; Wang, Jia; Zheng, Siwen; Xiao, Shengyuan; Wang, Yingping

    2017-11-01

    After cultivation of ginseng, ginsenosides, which are the major active ingredients of gingeng, were approved for use by the food industry, and began to be used as added functional ingredients to try to improve the quality and price of functional foods. However, the interaction between different types of ginsenosides and nutrients needs further study. We investigated the effect of B-complex vitamins (which are essential nutrients) on the pharmacokinetics of the ginsenosides protopanaxatriol-type saponin Rg1, protopanaxadiol-type saponin Rb1, and oleanolic acid-type saponin Ro after oral administration. Ginsenosides Rg1, Rb1, and Ro, with or without B-complex vitamins, respectively, were administered orally to rats to evaluate their pharmacokinetics. The concentration of ginsenosides in plasma was determined by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were fitted using WinNonlin v6.2. After oral coadministration with B-complex vitamins, the area under the concentration-time curve from zero to infinity (AUC0-∞) of ginsenoside Rg1 was reduced by 70%, that of ginsenoside Rb1 was reduced by 43%, and that of ginsenoside Ro was reduced by 34%. The AUC0-∞ of ginsenosides Rg1 and Rb1 showed significant differences between different treatments, but the AUC0-∞ of ginsenoside Ro did not. These results suggest significant ginsenoside-nutrient interactions between ginsenosides Rg1, Rb1, and B-complex vitamins.

  16. Administration of Anesthesia

    Science.gov (United States)

    ... a Surgeon What We Do Administration of Anesthesia Administration of Anesthesia Oral and maxillofacial surgeons are extensively ... Injury Wisdom Teeth Management Procedures Administration of Anesthesia Administration of Anesthesia Oral and maxillofacial surgeons are extensively ...

  17. Disappearance of a uterine arteriovenous malformation following long-term administration of oral norgestrel/ethinyl estradiol.

    Science.gov (United States)

    Oride, Aki; Kanasaki, Haruhiko; Miyazaki, Kohji

    2014-06-01

    Uterine arteriovenous malformation (AVM) can cause sudden massive hemorrhage. We report a case of uterine AVM following curettage in a patient treated conservatively with an intermediate-dose pill. An 18-year-old gravida 2 para 0 underwent curettage at 12 weeks of gestation and was examined for massive genital hemorrhage that occurred in postoperative month 4. Abundant blood flow in a mass within the uterine lumen was observed on color Doppler ultrasonography, and the patient was diagnosed with AVM. Six days after starting oral norgestrel/ethinyl estradiol, the hemorrhage ceased, and computed tomography on day 37 of administration showed disappearance of the abnormal vasculature. After 12 months, the patient's course remains favorable without relapse. Transarterial embolization for AVM can cause ovarian failure and subsequent placental malpositioning. Administration of oral norgestrel/ethinyl estradiol may be an alternative conservative treatment option for patients who wish to maintain fertility. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  18. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    Directory of Open Access Journals (Sweden)

    Kou-Zhu Zhu

    2013-01-01

    Full Text Available To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg, the native NNAV (untreated with heat; 90 μg/kg, and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

  19. Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

    Science.gov (United States)

    Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

    2018-02-01

    The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

  20. 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.

  1. Beneficial effects of long-term administration of an oral formulation of Angiotensin-(1-7) in infarcted rats.

    Science.gov (United States)

    Marques, Fúlvia D; Melo, Marcos B; Souza, Leandro E; Irigoyen, Maria Claúdia C; Sinisterra, Rúben D; de Sousa, Frederico B; Savergnini, Sílvia Q; Braga, Vinícius B A; Ferreira, Anderson J; Santos, Robson A S

    2012-01-01

    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.

  2. Oral administration of mesalazine protects against mucosal injury and permeation in dextran sulfate sodium-induced colitis in rats.

    Science.gov (United States)

    Hayashi, Yoshihiro; Aoyagi, Kunihiko; Morita, Isamu; Yamamoto, Chifumi; Sakisaka, Shotaro

    2009-01-01

    OBJECTIVE. Mesalazine, from which 5-aminosalicylic acid is released, is a therapeutic drug for inflammatory bowel disease. There has been no study concerning the effect of orally administered mesalazine on dextran sodium sulfate (DSS)-induced colitis in the rat model of ulcerative colitis. MATERIAL AND METHODS. Colitis was evaluated by means of the length of the colon, white blood cell count (WBC), tissue myeloperoxidase (MPO) activity, and histological inflammation scores. Colonic mucosal permeation was evaluated using Evans blue. The localization of a tight junction protein, occludin, was evaluated immunohistochemically and examined using confocal laser scanning microscopy. RESULTS. Mesalazine significantly improved changes in the length of the colon, tissue MPO activity, WBC, and the histological inflammation score as compared with DSS-induced colitis. Furthermore, the drug completely inhibited the increased permeation in DSS-induced colitis in rats. The immunofluorescence signals of occludin were disrupted and irregularly distributed in DSS-induced colitis, while the signals appeared as a typical reticular pattern but with reduced intensity by the administration of mesalazine, without any reduction in the protein content. In addition, the oral administration of mesalazine significantly improved mucosal permeation, thereby protecting the intestinal mucosa against injury in DSS-induced colitis in rats. CONCLUSIONS. These findings suggest that the recovery of mucosal impairment due to treatment with mesalazine may be associated with the protection of the tight junction protein occludin in DSS-induced colitis.

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

    Science.gov (United States)

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

    2017-08-08

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

  4. Ex vivo antibacterial activity of levofloxacin against Escherichia coli and its pharmacokinetic profile following intravenous and oral administrations in broilers.

    Science.gov (United States)

    Lee, Hong Ki; DeVito, Virginia; Vercelli, Cristina; Tramuta, Clara; Nebbia, Patrizia; Re, Giovanni; Kovalenko, Kaspars; Giorgi, Mario

    2017-06-01

    The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage in the target animals is increasingly being recognized as vital for maximizing efficacy and minimizing the risk of resistance, so this study aimed to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) of levofloxacin in broilers. Using a parallel study design, each group of animals (n=20) received 5mg/kg of levofloxacin intravenously (IV) and orally (PO). Plasma, serum and tissues were collected for PK and PD studies. Plasma concentrations of levofloxacin were determined by HPLC. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined against E. coli, isolated in clinical broilers. Ex vivo antibacterial activity was evaluated using the time killing method. Mean values of terminal half-life for IV and PO groups were 6.93 and 8.09h, respectively. Following oral administration, the peak plasma concentration was achieved at 0.88h (Tmax). Mean value of oral bioavailability was 123.25%. Levofloxacin residues were found in all the tissues tested (muscle, liver, kidney and lung). Plasma concentration above 8× MIC lead to eradication of E. coli (incubation period of 24h). The results of ex vivo growth inhibition curves were consistent with the in vitro time-kill study. Levofloxacin showed dependent plasma concentration antibacterial activity against a clinical isolate of E. coli. According to the assessment of PK/PD relationship, administration of 5mg/kg of levofloxacin seems to be effective in killing E. coli. Also, simulated optimal dose based on the ex vivo PK/PD approach was 2.9mg/kg/day (bactericidal) to 4.3mg/kg/day (eradication) PO against E. coli (MIC=0.125μg/ml). Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Oral administration of transgenic barley expressing a Culicoides allergen induces specific antibody response.

    Science.gov (United States)

    Jonsdottir, S; Svansson, V; Stefansdottir, S B; Mäntylä, E; Marti, E; Torsteinsdottir, S

    2017-07-01

    Insect bite hypersensitivity is an immunoglobulin (Ig)E-mediated dermatitis of horses initiated by bites of midges of the genus Culicoides. Culicoides spp. are not indigenous to Iceland and the prevalence of insect bite hypersensitivity is much higher in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. Immunotherapy is therefore needed. The aim of the study was to express an allergen from Culicoides in barley grain and investigate whether an immune response could be obtained in healthy Icelandic horses by oral treatment with transgenic barley expressing the allergen. In vivo experiment. The allergen was expressed in barley grain with the Orfeus technique. A device was developed to treat horses orally with barley flour. Four Icelandic horses were treated with transgenic barley and 3 with control barley, in total 500 g in 7 feedings. Serum and saliva samples were collected for measuring specific antibodies. The allergen Cul n 2, a hyaluronidase originating from the salivary gland of Culicoides nubeculosus, was expressed in barley. Horses treated with the transgenic barley mounted a Cul n 2 specific IgG1 and IgG4/7 response in serum and saliva. The serum response was significantly different between the transgenic and control barley treated horses for both subclasses and the saliva response for IgG1. The induced serum antibodies bound to the corresponding allergen from Culicoides obsoletus, rCul o 2 and were able to partially block binding of Cul n 2 as well as Cul o 2 specific IgE from insect bite hypersensitivity affected horses. Small number of horses. This study shows that specific antibody response can be induced in horses not exposed to Culicoides, using oral treatment with transgenic barley expressing an allergen. Further studies will determine whether this approach is a useful alternative for prevention and treatment of equine insect bite hypersensitivity. © 2016 EVJ Ltd.

  6. Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration.

    Science.gov (United States)

    Chen, Yin Bin; Wang, Yu Fang; Hou, Wei; Wang, Ying Ping; Xiao, Sheng Yuan; Fu, Yang Yang; Wang, Jia; Zheng, Si Wen; Zheng, Pei He

    2017-04-01

    Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from 11,830.85 ± 2,366.47 h·ng/mL to 890.55 ± 372.94 h·ng/mL. The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

  7. Pharmacokinetics and Bioavailability of a Fixed-Dose Combination of Ibuprofen and Paracetamol after Intravenous and Oral Administration.

    Science.gov (United States)

    Atkinson, Hartley C; Stanescu, Ioana; Frampton, Chris; Salem, Isam I; Beasley, Charles P H; Robson, Richard

    2015-10-01

    Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation. A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90% confidence intervals. The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125% acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78%) and ibuprofen (96.45%) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination. Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of

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

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    /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...... on the biopharmaceutical aspects of drug absorption and distribution both in vitro and in vivo. The aim of this review is to provide an overview of the different lipid-based dosage forms from a biopharmaceutical point of view and to describe effects of lipid dosage forms and lipid excipients on drug solubility, absorption...

  9. 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...

  10. 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.

  11. Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice.

    Science.gov (United States)

    Wang, Zhenbin; Wang, Qing; Wang, Lin; Xu, Weidong; He, Yuanqing; Li, Yunliang; He, Song; Ma, Haile

    2017-07-01

    Collagen hydrolysates (CHs) have been demonstrated to have positive effects on skin photoaging by topical application or oral ingestion. However, there has been little research on their influence on skin chronological aging. In this study, 9-month-old female ICR mice were given normal AIN-93M diets containing CHs (2.5, 5 and 10% w/w) from Nile tilapia scale. After 6 months, the collagen content and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities increased significantly (P skin did not change (P > 0.05). The color, luster and quantity of hair were obviously ameliorated. Moreover, the structure of epidermis and dermis, the density and distribution of collagen fibers and the ratio of type I to type III collagen were improved in a dose-dependent manner as shown by histochemical staining. Oral ingestion of CHs increased the collagen content and antioxidant enzyme activities and improved the appearance and structure of skin. These results suggest the potential of CHs as an anti-skin-aging ingredient in nutraceuticals or functional foods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.

    Directory of Open Access Journals (Sweden)

    Tamhane M

    1997-01-01

    Full Text Available Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex were divided into four groups as follows--Group 1 (n = 15 normal animals; Group II (n = 6 rats administered metoclopramide (1.35 mg/kg; Group III (n = 8 rats given atropine (0.45 mg/kg. These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8 were administered Terminalia chebula (100 mg/kg/day for 15 days orally. Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5% mixed with phenol red (50 mg/100 ml orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01 and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01. Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01. Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.

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

    Directory of Open Access Journals (Sweden)

    Athanassios Fragoulis

    2017-08-01

    Conclusion: In summary, these findings show that methysticin administration activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative damage and memory loss in a mouse model of AD. Therefore, kavalactones might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.

  14. Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging

    NARCIS (Netherlands)

    Rest, van de Ondine; Bloemendaal, Mirjam; Heus, De Rianne; Aarts, Esther

    2017-01-01

    The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

  15. Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study.

    Science.gov (United States)

    Solari, S; Cancino, A; Wolff, R; Norero, B; Vargas, J I; Barrera, F; Guerra, J F; Martínez, J; Jarufe, N; Soza, A; Arrese, M; Benitez, C

    2017-05-01

    Per-oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established. To compare tacrolimus drug exposure after sublingual and oral administration in liver transplant recipients. Experimental, open-label, non-randomised, cross-over study. Tacrolimus exposure was evaluated in 32 liver transplant recipients receiving oral administration. 12 h tacrolimus area-under-the-curve (AUC0-12 h ) was calculated using tacrolimus blood concentrations at 0-0.5-1-2-4-6-8-12 hrs post-dose. Recipients were switched to sublingual administration, and dose was adjusted to reach similar trough levels, new AUC0-12 h was calculated. Correlation between AUC0-12 h and trough levels was determined for both oral and sublingual phases. Similar trough levels were accomplished with oral and sublingual administration (6.68 ± 2 ng/mL vs. 6.62 ± 1.9 ng/mL (P = 0.8)). Although concentration 2 h post dose was higher in oral phase (15.36 ± 7.14 vs. 13.18 ± 5.64, P = 0.015), AUC0-12 h was similar in both phases (116.6 ± 34.6 vs. 111.5 ± 36.93 ng/mL* h, P = 0.19). Daily dose of tacrolimus required in sublingual phase was 37% lower than that used in oral phase (P tacrolimus when employing sublingual route. Good correlation between AUC0-12 h and trough levels was observed in sublingual phase (r2 = 0.74). Twenty-two recipients were maintained on sublingual administration after the end of study (mean follow-up: 18.7 ± 5.8 months). No difference in liver function tests or rejection rates was found during follow-up period. Sublingual administration of tacrolimus is feasible and provides similar drug exposure compared with oral administration. In our study, at long-term follow-up, sublingual administration was not associated with liver transplant rejection. © 2017 John Wiley & Sons Ltd.

  16. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

    Directory of Open Access Journals (Sweden)

    Nicholas A Young

    Full Text Available Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

  17. 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)

  18. 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.

  19. Facile hydrolysis of mebeverine in vitro and in vivo: negligible circulating concentrations of the drug after oral administration.

    Science.gov (United States)

    Dickinson, R G; Baker, P V; Franklin, M E; Hooper, W D

    1991-10-01

    The HPLC methods for the determination of plasma concentrations of the antispasmodic agent mebeverine (0.01-10 micrograms/mL) and its hydrolysis product veratric acid (0.1-50 micrograms/mL) are presented. Mebeverine was demonstrated to hydrolyze readily in fresh unbuffered human and rat plasma samples ex vivo. Hydrolysis in human plasma was completely inhibited in the presence of the esterase inhibitor physostigmine sulfate, at a concentration of 130 micrograms/mL. However, the inhibitor was only partially effective in blocking mebeverine hydrolysis in rat plasma. After oral administration of mebeverine.HCl (270 mg) to fasted human volunteers, measurable concentrations of the drug were not found in plasma. By contrast, the metabolite veratric acid achieved considerable concentrations (mean peak plasma concentration of 13.5 micrograms/mL at 40-80 min). After iv administration of mebeverine.HCl (2 mg) to rats, the drug was rapidly eliminated from plasma (mean half-life of 29 min) with simultaneous appearance of veratric acid (mean peak plasma concentration of 1.80 micrograms/mL at 15-30 min). However, after oral administration of the same dose, only traces of mebeverine were found in plasma, with the exception of one rat. Veratric acid again achieved considerable concentrations (mean peak plasma concentration of 0.90 micrograms/mL at 15 min-4 h). The results show that mebeverine undergoes rapid and extensive first-pass metabolism involving hydrolysis of the ester function, and that negligible circulating concentrations of the parent drug are found in humans.

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

    Science.gov (United States)

    Martín-Moreno, Ana María; Brera, Begoña; Spuch, Carlos; Carro, Eva; García-García, Luis; Delgado, Mercedes; Pozo, Miguel A; Innamorato, Nadia G; Cuadrado, Antonio; de Ceballos, María L

    2012-01-16

    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. 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). 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. In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.

  1. Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice.

    Science.gov (United States)

    Aoki, Shiho; Iwai, Atsushi; Kawata, Koji; Muramatsu, Daisuke; Uchiyama, Hirofumi; Okabe, Mitsuyasu; Ikesue, Masahiro; Maeda, Naoyoshi; Uede, Toshimitsu

    2015-07-16

    Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD, and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally, and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD).

  2. Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.

    Science.gov (United States)

    Abbo, Lisa A; Ko, Jeff C H; Maxwell, Lara K; Galinsky, Raymond E; Moody, David E; Johnson, Brenda M; Fang, Wenfang B

    2008-01-01

    Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.

  3. Sumatriptan (oral route of administration) for acute migraine attacks in adults

    Science.gov (United States)

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Objectives To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during

  4. 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.

  5. Acute and Chronic Effects of Oral Genistein Administration in Neonatal Mice1

    Science.gov (United States)

    Cimafranca, Melissa A.; Davila, Juanmahel; Ekman, Gail C.; Andrews, Rachel N.; Neese, Steven L.; Peretz, Jackye; Woodling, Kellie A.; Helferich, William G.; Sarkar, Jhimly; Flaws, Jodi A.; Schantz, Susan L.; Doerge, Daniel R.; Cooke, Paul S.

    2010-01-01

    Soy-based infant formulas are widely used in the United States and some other countries. These formulas contain high levels of the estrogenic isoflavone genistein, leading to concern that neonatal genistein exposure could cause acute and/or long-term adverse effects on reproductive and other organs. However, previous work to assess genistein effects in rodent models has not typically replicated the route of delivery and/or serum genistein concentrations reported for soy formula-fed human infants. Our objective was to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants. Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and nonreproductive organs were assessed after dosing and during subsequent development. Neonatal treatment resulted in changes both at the completion of dosing (PND 5) and in adult animals. At PND 5, neonatal genistein treatment caused increased relative uterine weight and down-regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (MOFs) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age despite normal fertility in these mice. The immediate and long-term effects in this neonatal animal model raise concerns that high serum concentrations of genistein are estrogenic and could potentially impact the development of human infants fed soy formula. PMID:20357267

  6. Formation of methanol and formate in Wistar rats after oral administration of methylated rapeseed oil: a fuel for lamps.

    Science.gov (United States)

    Prinz, Soenke; Tiefenbach, Birgit; Kobow, Manfred; Hennighausen, Gerhard

    2006-01-01

    Low viscosity, low surface tension and low volatility are features of lamp oils contributing to chemical pneumonia that can occur after ingestion. Because lamp oils with such physico-chemical properties have been forbidden in the European Community from July 2000 onward, industry has developed different products, mostly based upon rapeseed oil. The fatty acids of these oils are methylated. The goal of this study is to demonstrate whether methanol is released in Wistar rats after oral administration of these new lamp oils. Applying a dose of 1 ml/kg body weight lamp oil, peak levels of methanol were reached at 1 h (54.6 +/- 18.6 microg/ml), methanol was not detectable at 8 h. After the instillation of 4 ml/kg of lamp oil peak levels occurred at 2 h (189.2 +/- 24.9 microg/ml). The metabolite formate increased with time, and was highest at 8 h after the administration of 1 ml/kg body weight lamp oil (32.9 +/- 2.9 microg/ml). Starvation before the administration of 1 ml/kg body weight lamp oil decreased the methanol serum concentrations, but the differences were not significant. Based upon these experimental data in rats, it can be concluded that in humans small amounts of methanol will be released after ingestion of these lamp oils. As these products are mainly ingested accidentally by toddlers in low quantities, the risk of a methanol intoxication seems to be very low.

  7. 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.

  8. 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.  

  9. Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

    Directory of Open Access Journals (Sweden)

    Ondine van de Rest

    2017-11-01

    Full Text Available The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60–75 years received a single administration of 100, 150, or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18–35 years received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210, and 240 min after tyrosine intake. Working memory was assessed using the N-back task at 90 min after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p < 0.001, and the plasma response was higher than for young adults with the same dose (p < 0.001. Load-dependent working memory performance decreased with higher doses of tyrosine (p = 0.048, especially in older adults with greater dose-dependent plasma tyrosine responses (p = 0.035. Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

  10. 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

  11. Oral administration of an ethanolic extract of Hypericum gentianoides attenuates spontaneous colitis in mdr1a -/- mice

    Directory of Open Access Journals (Sweden)

    Kelley M. K. Haarberg

    2016-05-01

    Full Text Available Background: Nutraceuticals (i.e., complementary and alternative medicines are gaining ground as therapeutic modalities for inflammatory and autoimmune disorders, primarily due to their low toxicity and high patient compliance. Several species of Hypericum have been shown to possess immunomodulatory capabilities in many disease models. However, the therapeutic potential of the chemically unique Hypericum gentianoides (HG is largely untested. We investigated the efficacy of an orally administered ethanolic extract of HG (HGEE to prophylactically inhibit/ameliorate the spontaneous colitis that develops in mdr1a deficient (mdr1a -/- mice. Methods: Beginning at six weeks of age, vehicle (5% ethanol, HGEE (4.8 mg/day or metronidazole (0.75 mg/mL were orally administered daily to mdr1a -/- or FVB WT mice until they reached 20 weeks of age or had lost ≥ 15 % of their body weight. Macroscopic disease assessment included measurement of weight loss, colon shortening, and combined colonic/cecal macroscopic lesion scores. Colonic/cecal inflammation was also scored histologically. Inflammatory responses were assessed using myeloperoxidase (MPO assay and analysis of serum cytokines/chemokines. Results: Daily administration of HGEE significantly (p < 0.05 delayed the onset of clinical signs of disease, reduced the associated morbidity, and attenuated macroscopic and microscopic disease/inflammatory scores in mdr1a -/- mice. After 14 weeks of treatment, there were no adverse macroscopic or microscopic effects observed following the daily administration of HGEE to wild type FVB mice. Histological evaluation of colonic tissue revealed a decrease in neutrophil infiltration in HGEE treated mdr1a -/- mice, which was substantiated by a significant decrease (p ≤ 0.05 in colonic MPO activity. Compared to vehicle treated mdr1a -/- mice, levels of G-CSF, KC, and TNFα were significantly lower in the serum of mdr1a -/- mice treated with HGEE. Conclusion: Oral

  12. Uptake and efflux of rhenium in cells exposed to rhenium diseleno-ether and tissue distribution of rhenium and selenium after rhenium diseleno-ether treatment in mice.

    Science.gov (United States)

    Collery, Philippe; Bastian, Gérard; Santoni, François; Mohsen, Ahmed; Wei, Ming; Collery, Thomas; Tomas, Alain; Desmaele, Didier; D'Angelo, Jean

    2014-04-01

    We proposed a new water-soluble rhenium diseleno-ether compound (with one atom of Re and two atoms of Se) and investigated the uptake of Re into the nucleus of malignant cells in culture exposed to the compound for 48 h and its efflux from the nucleus after a post-exposure period of 48 h, as DNA is the main target of Re. We also studied the distribution of both Re and Se in the main organs after an oral administration of 10 or 40 mg/kg Re diseleno-ether to mice for four weeks, five days-a-week. Re and Se concentrations were assayed by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using the Wilcoxon signed-rank test, comparing two related groups. We observed that Re was well incorporated into the nucleus of malignant cells in the most sensitive cells MCF-7, derived from human breast cancer, and that there was no efflux of Re. In contrast, in MCF-7 resistant cells (MCF-7 Mdr and MCF-7 R), A549 and HeLa cells, there was significant efflux of Re from the nucleus after the wash-out period. In mice, an important and dose-dependent uptake of both Re and Se was observed in the liver, with lower concentrations in kidneys. The lowest concentrations were observed in blood, lung, spleen and bones. There was a significant increase of Re concentrations in the blood, liver and kidney in mice treated with Re diseleno-ether at the dose of 40 mg/kg/24 h versus those treated at the dose of 10 mg/kg/24 h. There was a significant increase of Se concentrations in all tissues with the dose of Re diseleno-ether of 10 mg/kg/24 h versus controls, and a significant increase in the liver in mice treated with dose of Re diseleno-ether of 40 mg/kg/24h versus those treated with 10 mg/kg/24 h. We are the first to demonstrate that a compound combining Re and Se in a single molecule, is able to deliver Re and Se to the organism via an oral route, for cancer treatment.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract of Wattakaka volubilis in Wistar Female Rats

    Directory of Open Access Journals (Sweden)

    Velmani Gopal

    2014-09-01

    Full Text Available Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W. volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from 100-1000 μg/mL of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT, alkaline phosphatase (ALP, bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and α-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract’s administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis

  15. Oral administration of morphine versus ibuprofen to manage postfracture pain in children: a randomized trial.

    Science.gov (United States)

    Poonai, Naveen; Bhullar, Gina; Lin, Kangrui; Papini, Adam; Mainprize, David; Howard, Jocelyn; Teefy, John; Bale, Michelle; Langford, Cindy; Lim, Rodrick; Stitt, Larry; Rieder, Michael J; Ali, Samina

    2014-12-09

    Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain. We used a parallel group, randomized, blinded superiority design. Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine (0.5 mg/kg orally) or ibuprofen (10 mg/kg) for 24 hours after discharge. Our primary outcome was the change in pain score using the Faces Pain Scale - Revised (FPS-R). Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose. We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group. For both morphine and ibuprofen, we found a reduction in pain scores (mean pre-post difference ± standard deviation for dose 1: morphine 1.5 ± 1.2, ibuprofen 1.3 ± 1.0, between-group difference [δ] 0.2 [95% confidence interval (CI) -0.2 to 0.6]; dose 2: morphine 1.3 ± 1.3, ibuprofen 1.3 ± 0.9, δ 0 [95% CI -0.4 to 0.4]; dose 3: morphine 1.3 ± 1.4, ibuprofen 1.4 ± 1.1, δ -0.1 [95% CI -0.7 to 0.4]; and dose 4: morphine 1.5 ± 1.4, ibuprofen 1.1 ± 1.2, δ 0.4 [95% CI -0.2 to 1.1]). We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points (p = 0.6). Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group (56.1% v. 30.9%, p ibuprofen. However, morphine was associated with a significantly greater number of adverse effects. Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures. ClinicalTrials.gov, no. NCT01690780. © 2014 Canadian Medical Association or its licensors.

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

    OpenAIRE

    Jezdimirović Milanka; Aleksić Nevenka; Trailović Saša; Ivanović Saša; Jezdimirović Nemanja

    2012-01-01

    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 co...

  17. Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, Erica C; Valberg, Stephanie J; Godden, Sandra M; Finno, Carrie J; Murphy, Michael J

    2004-01-01

    To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). 2 healthy horses and 5 Thoroughbreds with RER. 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.

  18. 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.

  19. Tissue Distribution, Excretion, and Metabolic Profile of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis grossedentata) after Oral Administration in Rats.

    Science.gov (United States)

    Fan, Li; Tong, Qing; Dong, Weiwei; Yang, Guangjie; Hou, Xiaolong; Xiong, Wei; Shi, Chunyang; Fang, Jianguo; Wang, Wenqing

    2017-06-14

    Dihydromyricetin (DMY), a flavanonol compound found as the most abundant and bioactive constituent in vine tea (Ampelopsis grossedentata), possesses numerous biological activities. In the present study, an HPLC-MS/MS method for the determination of DMY in tissues, urine, and feces was developed and applied to the tissue distribution and excretion study after oral administration in rats, and the metabolic profile of DMY was further investigated using UPLC-QTOF-MS. The results indicated that DMY could be distributed rapidly in various tissues and highly in the gastrointestinal tract. The elimination of DMY occurred rapidly as well, and most unconverted forms were excreted in feces. A total of eight metabolites were identified in urine and feces, while metabolites were barely found in plasma. The predicted metabolic pathways including reduction, dehydroxylation, methylation, glucuronidation, and sulfation were proposed. The present findings may provide the theoretical basis for evaluating the biological activities of DMY and will be helpful for its future development and application.

  20. Development of a Prodrug of Levofloxacin to Avoid Chelation with Al3+ and of Pemetrexed Dimedoxomil Esters for Oral Administration.

    Science.gov (United States)

    Matsuyama, Kenji

    2017-01-01

    An ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) avoids insoluble chelate formation with metal-containing drugs in the intestinal tract and is rapidly hydrolyzed to the parent drug. Furthermore, the minimum inhibitory concentration confirms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria flora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after modification of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with trifluoroacetic acid (TFA) in CH2Cl2 at a temperature of 0°C for 2 h. A serum pemetrexed concentration of >2 μg/mL was observed after oral administration of pemetrexed dimedoxomil at a dose of 60 mg/kg to rats.

  1. 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.

  2. Radioimmunoassay of plasma lisuride in man following intravenous and oral administration of lisuride hydrogen maleate: effect on plasma prolactin level.

    Science.gov (United States)

    Hümpel, M; Nieuweboer, B; Hasan, S H; Wendt, H

    1981-01-01

    The development of a sensitive radioimmunoassay for the determination of lisuride in plasma is described. The antiserum against lisuride-4-hemisuccinate-BSA was raised in rabbits. Using this method the plasma levels of lisuride were monitored following one intravenous (25 microgram) and two oral (100 microgram and 300 microgram) doses of lisuride hydrogen maleate in three female and three male volunteers (intra-individual comparison). The plasma prolactin was also determined by radioimmunoassay. Following i. v. injection, the concentration of lisuride declined in three phases, with half-lives of 5 min, 25 min and 2 h. The total plasma clearance of 800 +/- 250 ml X min-1 was in the range of "plasma flow" through the liver. In agreement with the high rate of biotransformation, the bioavailability of lisuride administered orally was 10% +/- 7% of the 100-microgram dose, and 22% +/- 7% of the 300-microgram dose. The plasma prolactin was lowered to 3%-18% of its pretreatment value depending on the route of administration and the dose. The reduction appeared to be short-lived and to be directly dependent on the plasma concentration of lisuride. Following intravenous injection, the prolactin level declined after a so far unexplained lag-time of 0.5 h.

  3. Changes in Bioavailability of Omega-3 (DHA) through Alpha-Tocopheryl Phosphate Mixture (TPM) after Oral Administration in Rats.

    Science.gov (United States)

    Libinaki, Roksan; Gavin, Paul D

    2017-09-20

    Benefits of Omega-3 Docosahexaenoic acid (DHA) supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM), following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg) or low dose (88.6 mg/kg) of DHA. TPM was examined at 1:0.1 w/w (low TPM dose) and 1:0.5 w/w (high TPM dose). Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL) and AUC values (1396.60 and 1560.60) for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont) and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns) and 50% (p DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90%) the LDC control (p = 0.057). This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

  4. Oral administration of an aqueous extract from the oyster mushroom Pleurotus ostreatus enhances the immunonutritional recovery of malnourished mice.

    Science.gov (United States)

    Llauradó, Gabriel; Morris, Humberto J; Lebeque, Yamila; Venet, Gleymis; Fong, Onel; Marcos, Jane; Fontaine, Roberto; Cos, Paul; Bermúdez, Rosa C

    2016-10-01

    Mushroom nutriceutical components have lately attracted interest for developing immunonutritional support. However, there is relatively little information pertaining to the use of mushroom preparations for modulating the metabolic and immunological disorders associated to malnutrition. This study was aimed to evaluate the effects of oral administration of an aqueous extract (CW-P) from Pleurotus ostreatus on the recovery of biochemical and immunological functions of malnourished mice. 8-week old female BALB/c mice were starved for 3days and then refed with commercial diet supplemented with or without CW-P (100mg/kg) for 8days. Regardless of the diet used during refeeding, animal body weights and serum protein concentrations did not differ between groups. Oral treatment with CW-P normalized haemoglobin levels, liver arginase and gut mucosal weight. CW-P increased total liver proteins and also DNA and protein contents in gut mucosa. Pleurotus extract provided benefits in terms of macrophages activation as well as in haemopoiesis, as judged by the recovery of bone marrow cells and leukocyte counts. Moreover, CW-P stimulated humoral immunity (T-dependent and T non-dependent antibodies responses) compared to non-supplemented mice. CW-P extract from the oyster mushroom can be used to develop specific food or nutritional supplement formulations with potential clinical applications in the immunotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Changes in Bioavailability of Omega-3 (DHA through Alpha-Tocopheryl Phosphate Mixture (TPM after Oral Administration in Rats

    Directory of Open Access Journals (Sweden)

    Roksan Libinaki

    2017-09-01

    Full Text Available Benefits of Omega-3 Docosahexaenoic acid (DHA supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM, following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg or low dose (88.6 mg/kg of DHA. TPM was examined at 1:0.1 w/w (low TPM dose and 1:0.5 w/w (high TPM dose. Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL and AUC values (1396.60 and 1560.60 for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns and 50% (p < 0.05 increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90% the LDC control (p = 0.057. This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

  6. Effect of food intake on the pharmacokinetics of sarpogrelate and its active metabolite following oral administration to beagle dogs.

    Science.gov (United States)

    Baek, In-Hwan; Lee, Byung-Yo; Kim, Min-Soo; Kwon, Kwang-Il

    2013-10-01

    1. The objectives of this study were to develop a pharmacokinetic model for sarpogrelate and its metabolite M-1 and to identify the effect of food on sarpogrelate and M-1 pharmacokinetics in beagle dogs. 2. A single 100 mg oral dose of sarpogrelate was administered to fasted and fed beagle dogs and the plasma concentrations of sarpogrelate and M-1 were measured simultaneously by liquid chromatography tandem mass spectrometry. The resultant data were analyzed by modeling approaches using ADAPT5. 3. The plasma concentration time course of sarpogrelate and M-1 were described using a parent-metabolite compartment model with first-order absorption and elimination. The systemic exposure of sarpogrelate and its metabolite after the administration of a single 100 mg oral dose was significantly decreased under the fed condition compared to that under the fasting condition. Modeling approaches have sufficiently explained the food effect of sarpogrelate, i.e. an increased Vc and decreased Ka, in fed dogs. The food effect of sarpogrelate was due to its pH-dependent dissolution. 4. These findings suggest that food intake affects both the rate and extent of absorption of sarpogrelate, and that the pharmacological effect of sarpogrelate can differ significantly according to food intake.

  7. Comparative Analysis of the Effectiveness of the Topical Administration of Benzocaine and EMLA® on Oral Pain and Tactile Sensitivity

    Directory of Open Access Journals (Sweden)

    David Gomes de Alencar Gondim

    2018-01-01

    Full Text Available Objectives. To compare the effectiveness of the topical administration of benzocaine and EMLA on oral pain and tactile sensitivity. Materials and Methods. A randomized, double-blind, split-mouth clinical trial was carried out with 20 volunteers. The sensorial and quantitative tests were applied before the contact with topical anesthetic and after the application. Results. In the superficial tactile perception test, when we compared each group singly, there were statistically significant values in the decrease of superficial tactile perception when compared to the moment prior to the application of anesthetic agents. For the sensitivity to mechanical pain, no statistical significant difference was observed at evaluated times. In the needle penetration test, in an intergroup analysis, we found a decrease in the pain sensitivity to needle penetration at 5 min (p=0.053 and at 10 min (p=0.019 after the contact of the anesthetic drug with the oral mucosa. Conclusion. The application of topical anesthetic drugs reduces the discomfort associated with this procedure, mainly until the first 10 minutes. Only the needle penetration sensitivity test showed sufficient sensitivity to reveal a difference in the anesthetic effect between EMLA and benzocaine. This trial is registered with RBR-2N2GSW.

  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. Decreased Absorption of Dolutegravir and Tenofovir Disoproxil Fumarate, But Not Emtricitabine, in an HIV-Infected Patient Following Oral and Jejunostomy-Tube Administration.

    Science.gov (United States)

    Brooks, Kristina M; Garrett, Katy L; Kuriakose, Safia S; George, Jomy M; Balba, Gayle; Bailey, Bria; Anderson, Megan; Lane, H Clifford; Maldarelli, Frank; Pau, Alice K

    2017-08-01

    The use of enteral feeding tubes to administer antiretroviral medications is necessary in certain patients with human immunodeficiency virus (HIV) infection. However, adequacy of drug exposures after these administration routes are largely unknown, making dosing recommendations and the attainment of viral suppression challenging in this patient population. This report describes a patient with advanced HIV infection and a complicated medical history including long-term intractable nausea/vomiting necessitating antiretroviral medication administration via a Roux-en-Y jejunostomy (J)-tube. Pharmacokinetic assessments were performed to compare differences in antiretroviral drug absorption and plasma exposure following oral and J-tube administration of dolutegravir, tenofovir disoproxil fumarate, and emtricitabine. Results were also compared with published pharmacokinetic data in HIV-infected individuals. Exposure to dolutegravir and tenofovir were similar between J-tube and oral administration routes, whereas emtricitabine exposure was 38% lower when administered via J-tube. However, in comparison with reference data in HIV-infected individuals taking these medications orally, exposure to dolutegravir and tenofovir was 75-76% and 55-61% lower, respectively, following both routes of administration. Emtricitabine exposure was similar to and 71% higher than reference data following J-tube and oral administration, respectively. This report highlights the importance of performing pharmacokinetic assessments in patients with the potential for impaired drug absorption to ensure antiretroviral treatment success. © 2017 Pharmacotherapy Publications, Inc.

  10. [Effect of intermittent rehydration therapy as an oral and enteral rehydration solution, alone or in combination with intravenous administration on intravascular dehydration].

    Science.gov (United States)

    Takehisa, Yozo; Takehisa, Takahiro; Yamato, Kaoru; Kuramoto, Etsuko; Ikawa, Seiichiro

    2012-01-01

    The purpose of this study was to demonstrate the effectiveness of intermittent fluid infusion (intermittent rehydration therapy) to dehydrated elderly patients and the efficacy of Heisei Solution Water (HSW), an oral and enteral rehydration solution developed by our group. We enrolled 375 elderly patients with suspected dehydration from among 1,921 patients of our hospital and 13 affiliated hospitals. A total of 36 of 375 patients received intermittent rehydration therapy. These patients were then divided into 3 groups according to the method of administration: (1) oral and enteral administration (n=16), (2) intravenous administration only (n=10) and (3) combined oral, enteral and intravenous administration (n=10). We then compared blood urea nitrogen/creatinine (BUN/Cr) ratios among the 3 groups. BUN/Cr ratios were improved in all groups, but there was no statistically significant difference in the degree of improvement of BUN/Cr ratios among the 3 groups. Intermittent rehydration therapy is a highly effective way to manage dehydration. The intermittent oral and enteral administration of HSW demonstrated the same effectiveness as other forms of administration.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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%.

  13. Effect of oral administration of AZD8309, a CXCR2 antagonist, on the severity of experimental pancreatitis.

    Science.gov (United States)

    Malla, Sudarshan R; Kärrman Mårdh, Carina; Günther, Annett; Mahajan, Ujjwal M; Sendler, Matthias; D'Haese, Jan; Weiss, Frank Ulrich; Lerch, Markus M; Hansen, Mark Berner; Mayerle, Julia

    2016-01-01

    Acute pancreatitis is a common gastrointestinal disorder burdened with a high mortality. Two pathophysiological events during experimental pancreatitis are thought to determine the clinical course: premature digestive protease activation and tissue infiltration by inflammatory cells. We have investigated the effect of AZD8309, a potent and orally bioavailable antagonist of the chemokine receptor CXCR2, which has been proposed to regulate the transmigration of neutrophils. Male C57BL6 mice (25-30 g) received gavage feeding of AZD8309 (50 mg/kg/BW) or mannitol (controls) twice daily starting 3 h prior to pancreatitis induction. Mild pancreatitis was induced by i.p. caerulein administration (50 μg/kg BW), severe pancreatitis by intraductal taurocholate (2%). Pancreas, lung, and serum was harvested up to 48 h after pancreatitis induction and used for histopathology, amylase, lipase, cathepsin B, trypsin, and elastase activity measurements, myeloperoxidase (MPO) content and cytokine concentrations. Oral administration of AZD8309 significantly reduced MPO in the pancreas and lungs (8 h & 24 h) and reduced intrapancreatic trypsin and elastase activity (8 h) in caerulein-pancreatitis. In taurocholate-pancreatitis AZD8309 reduced cathepsin B activity and MPO. Serum cytokine levels were reduced by AZD8309 as well as histopathological damage. The CXCR2 antagonist AZD8309 reduced the transmigration of neutrophils as well as intrapancreatic protease activation in experimental pancreatitis. This effect was sufficient to reduce the overall severity of the disease. CXCR2 may therefore be a viable therapeutic target and AZD8309 a suitable agent for the treatment of acute pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  14. Characterization of proteinuria and tubular protein uptake in a new model of oral L-lysine administration in rats.

    Science.gov (United States)

    Thelle, K; Christensen, E I; Vorum, H; Ørskov, H; Birn, H

    2006-04-01

    Intravenous infusion of basic amino acids is used experimentally and pharmacologically to prevent renal proximal tubular uptake of filtered proteins. Intravenously injected L-lysine is rapidly cleared from plasma and the effect on tubular protein reabsorption is transient. To obtain a more sustained effect, we developed a model of oral L-lysine administration and characterized this model by analyzing urinary protein excretion and proximal tubule uptake of filtered proteins. Rats placed in metabolic cages were treated with 20 mmol/kg/6 h of L-lysine, glycine, or water. Urines were analyzed for proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and radioimmunoassay. Proximal tubule uptake of proteins and expression of apical membrane receptors were investigated by immunocytochemistry. In vitro uptake and receptor expression were studied using a yolk sac cell line. L-lysine administration produced increased urinary excretion of a large number of proteins while the effect on tubular accumulation of selected proteins was variable. L-lysine treatment induced changes in the localization of two receptors responsible for tubular endocytosis of filtered proteins. In conclusion, oral L-lysine treatment induced proteinuria, in particular albuminuria, as efficiently as previous reports on intravenous infusion. The effect on tubular protein accumulation was variable suggesting differential effects on tubular reabsorption and degradation of filtered proteins. Changes in tubular protein handling were accompanied by changes in the localization of the endocytic receptors, megalin, and cubilin. In vitro experiments supported the in vivo observations. The findings suggest that L-lysine may affect receptor trafficking in addition to possible effects on the direct binding of ligands to the receptors.

  15. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

    Science.gov (United States)

    Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

    2007-03-01

    To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

  16. Oral Administration to Nursing Women of Lactobacillus fermentum CECT5716 Prevents Lactational Mastitis Development: A Randomized Controlled Trial

    Science.gov (United States)

    Hurtado, José A.; Maldonado-Lobón, Jose A.; Díaz-Ropero, M. Paz; Flores-Rojas, Katherine; Uberos, José; Leante, José L.; Affumicato, Laura; Couce, María Luz; Garrido, José M.; Olivares, Mónica

    2017-01-01

    Abstract Objective: The objective of this study is to evaluate the preventive effect of oral administration of Lactobacillus fermentum CECT5716 on mastitis incidence in lactating women. Methods: A randomized double-blinded controlled trial that included 625 women was conducted. Women who received preventive dose of antibiotic in the context of delivery were recruited 1–6 days after childbirth and randomly assigned to a group. Probiotic group received 1 capsule/day containing L. fermentum 3 × 109 CFU, control group received 1 placebo capsule/day containing maltodextrin. The intervention period was 16 weeks. The primary outcome of the study was the incidence of clinical mastitis defined as at least two out of the three breast symptoms (pain, redness, and lump) and at least one of fever or flu-like symptoms (shivering, hot sweats, or aches). Results: Two hundred ninety-one women completed 16 weeks of treatment. Sixteen women in the probiotic group developed mastitis versus 30 women in the control group (odds ratio = 0.531; p = 0.058). Incidence rate of mastitis in the probiotic group was significantly lower than that in the control group (IR = 0.130 in the probiotic group versus IR = 0.263 in the control group; p = 0.021). Therefore, the oral administration of L. fermentum CECT5716 during lactation decreased by 51% the incidence rate of clinical mastitis. Staphylococcus spp. load at the end of intervention was significantly lower in breast milk of women in the probiotic group than in breast milk of women in the control group (p = 0.025). Conclusion: Consumption of the probiotic strain L. fermentum CECT5716 might be used during breastfeeding as an efficient strategy to prevent development of lactational mastitis in women. Trial registration: NCT02203877.

  17. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

    1986-11-01

    RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

  18. Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study.

    Science.gov (United States)

    van Dijkhuizen, E H Pieter; Pouw, Juliëtte N; Scheuern, Andrea; Hügle, Boris; Hardt, Sven; Ganser, Gerd; Kümmerle-Deschner, Jasmin Beate; Horneff, Gerd; Holzinger, Dirk; Bulatović Ćalasan, Maja; Wulffraat, Nico M

    2016-01-01

    Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials.

  19. Oral administration of melatonin counteracts several of the effects of chronic stress in rainbow trout.

    Science.gov (United States)

    Conde-Sieira, M; Muñoz, J L P; López-Patiño, M A; Gesto, M; Soengas, J L; Míguez, J M

    2014-01-01

    To assess a possible antistress role of melatonin in fish, we orally administered melatonin to rainbow trout for 10 d and then kept the fish under normal or high stocking density conditions during the last 4 d. Food intake; biochemical parameters in plasma (cortisol, glucose, and lactate concentrations); liver (glucose and glycogen concentrations, and glycogen synthase activity); enzyme activities of amylase, lipase, and protease in foregut and midgut; and content of the hypothalamic neurotransmitters dopamine and serotonin, as well as their oxidized metabolites, 3,4-dihydroxyphenylacetic acid and 5-hydroxy-3-indoleacetic acid, were evaluated under those conditions. High stocking density conditions alone induced changes indicative of stress conditions in plasma cortisol concentrations, liver glycogenolytic potential, the activities of some digestive enzymes, and the 3,4-dihydroxyphenylacetic acid-to-dopamine and 5-hydroxy-3-indoleacetic acid-to-serotonin ratios in the hypothalamus. Melatonin treatment in nonstressed fish induced an increase in liver glycogenolytic potential, increased the activity of some digestive enzymes, and enhanced serotoninergic and dopaminergic metabolism in hypothalamus. The presence of melatonin in stressed fish resulted in a significant interaction with cortisol concentrations in plasma, glycogen content, and glycogen synthase activity in liver and dopaminergic and serotoninergic metabolism in the hypothalamus. In general, the presence of melatonin mitigated several of the effects induced by stress, supporting an antistress role for melatonin in rainbow trout. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review.

    Science.gov (United States)

    Batchelor, Hannah K

    2015-06-09

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food-drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food-drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food-drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food-drug interactions within paediatric populations.

  1. Transmission of (/sup 14/C)deoxynivalenol to eggs following oral administration to laying hens

    Energy Technology Data Exchange (ETDEWEB)

    Prelusky, D.B.; Trenholm, H.L.; Hamilton, R.M.G.; Miller, J.D.

    Following a single oral dose of (/sup 14/C)deoxynivalenol (2.2 mg of DON, 2.4 ..mu..Ci/bird) low levels of residues were transmitted to eggs. Maximum radioactivity, which occurred in the first eggs laid after dosing (within 24 h), amounted to 1.9 ..mu..g DON-equivalents/60-g egg (0.087% of dose) levels dropped rapidly in ensuing eggs. During daily consumption of DON, administered in spiked feed over a 12-day period (2.2 mg of DON/bird per day for 6 days followed by 2.2 mg of (/sup 14/C)DON, 1.5 ..mu..Ci/bird per day for 6 days), radioactivity levels increased with each subsequent egg laid up until the last exposure to the toxin; maximum levels accounted for 4.2 ..mu..g DON-equivalents/60-g egg. Residues quickly declined once the birds were switched to clean feed. Results indicate that although residues appear to accumulate in eggs, levels do not persist once the contaminated source is withdrawn. Preliminary analysis of egg material showed only about 10% of radioactivity present could be identified as the parent toxin, DON.

  2. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra.

    Science.gov (United States)

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    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.

  3. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    Science.gov (United States)

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.

  4. 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.

  5. Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration.

    Science.gov (United States)

    Polettini, Aldo; Cone, Edward J; Gorelick, David A; Huestis, Marilyn A

    2012-05-13

    Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)). MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg(-1) cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 ± 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r(2)=0.90, p=0.00) and AMP (r(2)=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C(max) and melanin. This study demonstrated that despite large inter

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

    Directory of Open Access Journals (Sweden)

    A Martso

    2008-01-01

    Results. There is evidence that patients tolerate both its sachets and tablets equally well, as confirmed by subjective and objective observations. There are neither marked side effects nor considerable changes in laboratory tests and in the values of vital functions. Diclofenac potassium as early-action tablets (50 and 100 mg exerts a very good analgesic effect in treating migraine since the plasma concentration of the drug peaks on an average of an hour of administration (range 0,33-2 hours and the analgesic effect developed following 60-90 min. Conclusion. By comparing the rate of absorption, it may be concluded that diclofenac potassium as sachets will produce a much rapider analgesic effect. Thus, the high solubility of diclofenac potassium and its very good absorbability (as sachets in particular make the drug a superior analgesic that has a rapid analgesic activity.

  7. Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

    Science.gov (United States)

    Sun, Wei; Sanapala, Shilpa; Rahav, Hannah; Curtiss, Roy

    2015-11-27

    A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Sun Woo Lim

    Full Text Available BACKGROUND: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. METHODS: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media. RESULTS: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

  9. Potential beneficial effects of oral administration of isoflavones in patients with chronic mountain sickness

    Science.gov (United States)

    CUI, JIANHUA; GAO, LIANG; YANG, HAIJUN; WANG, FULING; JIANG, CHUNHUA; GAO, YUQI

    2014-01-01

    Soy isoflavones (Ifs), which are natural phytoestrogens, have beneficial effects in cardiovascular disease. We have previously shown that genistein, the most active component of Ifs, inhibits pulmonary vascular structural remodeling and right ventricular hypertrophy induced by chronic hypoxia in male Wistar rats. This study aimed to evaluate the effects of Ifs on right ventricular and pulmonary hemodynamics in individuals with chronic mountain sickness (CMS). Twenty-eight male patients living on the Qinghai-Tibetan plateau (5,200 m) who were suffering from CMS were treated orally with Ifs (20 mg, twice daily) for 45 days. Physiological and plasma biochemical indices, hematology and echocardiography were investigated. It was observed that 45 days of treatment with Ifs significantly increased blood oxygen saturation and markedly decreased the CMS score and heart rate (all P<0.05) of the subjects. Following treatment with Ifs, hematocrit (P<0.05), hemoglobin concentration (P<0.01) and plasma levels of malondialdehyde (P<0.05) were significantly decreased, while plasma levels of nitric oxide (P<0.01) and the plasma activity of nitric oxide synthase (P<0.01) and superoxide dismutase (P<0.01) were markedly increased compared with the respective values obtained prior to treatment with Ifs. The echocardiography results showed that Ifs significantly decreased the main pulmonary artery diameter (P<0.05), right ventricular end-diastolic anteroposterior diameter (P<0.01), right ventricular end-diastolic trans diameter (P<0.01), right ventricular anterior wall (P<0.01) and right ventricular outflow tract (P<0.01). These results indicate the potential beneficial effects of Ifs in the reduction of excessive erythrocytosis, the alleviation of oxidative damage and the amelioration of right ventricular index and pulmonary hemodynamics in CMS. PMID:24348805

  10. ADMINISTRATION OF EARLY POST-PARTUM ORAL DRENCH IN DAIRY COWS: EFFECTON METABOLIC PROFILE

    Directory of Open Access Journals (Sweden)

    R. Schallenberger Gonçalves

    2015-01-01

    Full Text Available Some prophylactic treatments have been proposed in high-yielding dairy cattle in order to minimize the effects of negative energy balance and some disturbances such as hypocalcaemia and ketosis. The objective of this study was to evaluate the effects of two doses of d rench within 24 h after calving on the metabolic profile and prevention of ketosis. a total of 48 cows from a herd in r io Grande do s ul state (southern Brazil was used in the study. The animals were randomly selected and treated orally with d rench ( n = 32, propylene glycol, electrolytes and choline in 40 L of water and water ( n = 16 used as control. Blood samples were collected by blood coccygeal venipuncture through a vacutainer plain system tubes. Biochemical determinations were performed in serum (albumin, urea, cholesterol, triglycerides, non-esterified fatty acids - ne F a -, calcium, phosphorus, magnesium, aspartate transaminase - as T- and gammaglutamyl- transferase -GGT- and a cow-side determination of beta-hydroxybutyrate (BHB was performed using the a bbot blood Precision Xtra system. a ll cows in the experiment had their milk production controlled. The d rench treatment produces a tendency to a better milk yield (32.5 vs 29.6 L/cow/day and helps to prevent subclinical ketosis, as indicated by a lesser prevalence of subclinical ketosis (29.7% vs 37.2% and mean values of BHB (1.19 vs 1.27 mmol/L as well as a lesser lipolysis as indicated by ne F a values (509 vs 1.560 μmol/L. The other components of the metabolic profile did not have substantial effects between treatments. i n short, on the conditions of the present work, the d rench treatment is an effective management tool for prevention of subclinical ketosis and severe lipolysis.

  11. Major human milk oligosaccharides are absorbed into the systemic circulation after oral administration in rats.

    Science.gov (United States)

    Vazquez, E; Santos-Fandila, A; Buck, R; Rueda, R; Ramirez, M

    2017-01-01

    Human milk oligosaccharides (HMO) are involved in many biological functions influencing infant health. Although HMO act locally at the intestine, recent evidence has demonstrated that HMO are partially incorporated into the systemic circulation of breast-fed infants. In the last few years, a large amount of research has been conducted using preclinical models to uncover new biological functions of HMO. The aim of this study was to evaluate the absorption and urine excretion of HMO in rats. We administered a single oral dose of the following HMO: 2'-fucosyllactose (2'-FL), 6'-sialyllactose and lacto-N-neotetraose at different concentrations to adult rats. The time course of absorption of HMO into the bloodstream and their appearance in urine was studied. Our results showed that rats, similar to human infants, are able to effectively absorb a portion of HMO from the intestine into plasma and to excrete them in urine. On the basis of this, we also conducted a specific kinetic absorption study with 2'-FL, the most predominant HMO in human milk, in 9-11-d-old rat pups. Our results confirmed that a significant amount of 2'-FL was absorbed into the systemic circulation and subsequently excreted in urine during lactation in rats in a dose-depended manner. We also found basal levels of these HMO in plasma and urine of adult rats as well as rat pups as a natural result of nursing. Our data suggest that the rat may be a useful preclinical model that provides new insights into the metabolism and functions of HMO.

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

    Directory of Open Access Journals (Sweden)

    Prashant Kumar

    Full Text Available Zidovudine (AZT is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50-75% the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano. The nanoparticles (NPs are of 50-60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery.

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

    Science.gov (United States)

    C., Bhaskar; Golla, Kishore; Kondapi, Anand K.

    2015-01-01

    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. PMID:26461917

  14. Effects of oral administration of energy drinks on blood chemistry, tissue histology and brain acetylcholine in rabbits.

    Science.gov (United States)

    Ebuehi, O A T; Ajayl, O E; Onyeulor, A L; Awelimobor, D

    2011-01-01

    Energy drinks are canned or bottled carbonated beverages that contain large amounts of caffeine and sugar with additional ingredients, such as B-Vitamins, amino acids and herbal stimulants. Previous reports have shown that consumption of large amounts of these energy drinks may result in adverse health consequences. The present study is to ascertain if oral administration of energy drinks, such as "power horse" and "red bull", may affect blood chemistry, tissue histology and acetyl choline levels in rabbits. Five ml of power horse and red bull energy drinks, caffeine and saline (control) were orally administered daily for 36 days to rabbits. Body weight, feed and water intake were measured every other day. The blood samples were taken by cardiac puncture for blood chemistry measurement and their liver, heart and brain tissues were used for histological assay. The plasma, liver, brain and heart acetylcholine levels were also determined. There were no significant differences in the body weight, feed intake and organ weights of rabbits administered energy drinks or caffeine as compared to the control. The blood chemistry results showed that the activities of the aspartate and alanine amino transferase, concentrations of plasma creatinine, uric acid and albumin were increased in the control as compared to the red bull and caffeine administered rabbits. The concentrations of total protein, total cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL) and glucose concentrations were increased in power horse and red bull administered rabbits as compared to caffeine administered rabbits and control rabbits. The concentrations of plasma and brain acetylcholine of rabbits administered power horse and red bull were significantly higher than in the control, while it was lower in liver and heart acetyl choline levels. The histopathological findings of the brain and liver show that there were no obvious histopathological abnormalities in the

  15. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs.

    Directory of Open Access Journals (Sweden)

    Hirotaka Igarashi

    Full Text Available Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14, and 14 and 28 days after cessation (day 28 and 42. DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA gene sequences using next-generation sequencing (Illumina MiSeq. In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health

  16. Oral administration of a medium containing both D-aspartate-producing live bacteria and D-aspartate reduces rectal temperature in chicks.

    Science.gov (United States)

    Do, P H; Tran, P V; Bahry, M A; Yang, H; Han, G; Tsuchiya, A; Asami, Y; Furuse, M; Chowdhury, V S

    2017-10-01

    1. The aim of this study was to investigate the effects on the rectal temperature of young chicks of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chicks were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chicks were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature. In Experiment 3, after 1 week of chronic oral administration of the medium, 14-d-old chicks were exposed to either high ambient temperature (HT; 40 ± 1°C, 3 h) or control thermoneutral temperature (CT; 30 ± 1°C, 3 h) to monitor the changes in rectal temperature. 3. Chronic, but not acute, oral administration of the medium significantly reduced rectal temperature in chicks, and a chronic effect also appeared under HT conditions. 4. Chronic oral administration of the medium significantly reduced the mRNA abundance of the avian uncoupling protein (avUCP) in the breast muscle, but led to a significant increase in avian adenine nucleotide translocator (avANT) mRNA in the same muscle. 5. (a) These results indicate that the medium can reduce body temperature through the decline in avUCP mRNA expression in the breast muscle that may be involved in reduced mitochondrial proton leaks and heat production. (b) The increase in avANT further suggests a possible enhancement of adenosine triphosphate (ATP) synthesis.

  17. Cation permeable membranes from blends of sulfonated poly(ether ether ketone) and poly (ether sulfone)

    NARCIS (Netherlands)

    Wilhelm, F.G.; Punt, Ineke G.M.; van der Vegt, N.F.A.; Strathmann, H.; Wessling, Matthias

    2002-01-01

    Sulfonated poly(aryl ether ether ketone), S-PEEK, is blended with non-sulfonated poly(ether sulfone) (PES) to adjust the properties of ion permeable and ion selective membranes. In this study, membranes are prepared from blends with (i) a S-PEEK content between 10 and 100 wt.% using one S-PEEK batch

  18. Breathing patterns and levels of consciousness in children during administration of nitrous oxide after oral midazolam premedication.

    Science.gov (United States)

    Litman, R S; Kottra, J A; Berkowitz, R J; Ward, D S

    1997-12-01

    The combination of midazolam and nitrous oxide is commonly used to achieve sedation and analgesia during pediatric oral procedures, yet there are few, if any, data that illustrate the ventilatory effects of N2O in children, especially when used in combination with additional central nervous system (CNS) depressants. It was hypothesized that the addition of N2O inhalation to oral midazolam premedication would enhance the sedative effects of the midazolam and add analgesia without causing significant respiratory depression. The purpose of this study was to test this hypothesis. Thirty-four healthy children about to undergo restorative dental treatment under general anesthesia were premedicated with oral midazolam, 0.7 mg/kg, and were then exposed to 40% N2O for 15 minutes after a 5-minute control period. The effect of adding N2O on SpO2, respiratory rate, PETCO2, VT, and VT/TI was examined and the levels of consciousness (conscious vs deep sedation) before and during N2O inhalation were determined. During the course of the study, no child developed hypoxemia (SpO2 children who did not develop hypoventilation (defined as PETCO2 > 45 mm Hg) during the control period did so after initiation of N2O. Overall, there were no significant differences in SpO2, PETCO2, VT, or VT/TI between the control and study periods. However, respiratory rates were significantly higher in the first 10 minutes of N2O inhalation when compared with the control period. Before starting N2O administration, 14 children were not clinically sedated, 19 children met the criteria for conscious sedation, and one child met the criteria for deep sedation. At the end of 15 minutes of N2O inhalation, 12 children were not clinically sedated, 17 children met the definition of conscious sedation, three were deeply sedated, and one child had no response to IV insertion, implying a state of general anesthesia. There were no differences in sedation scores between the control and study periods (P = .6). Overall

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

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar; Mehrdana, F.; Hansen, Egon Bech

    2017-01-01

    The antimicrobial peptide CAP18 has been demonstrated to have a strong in vitro bactericidal effect on Yersinia ruckeri, but its activity in vivo has not been described. In this work, we investigated whether CAP18 protects rainbow trout Oncorhynchus mykiss (Walbaum) against enteric red mouth...... the conventional antibiotic oxolinic acid. Oral administration of CAP18 to trout did not prevent infection. The proteolytic effect of secretions on the peptide CAP18 in the fish gastrointestinal tract is suggested to account for the inferior effect of oral administration....

  20. 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.

  1. Keeping ether "en-vogue": the role of Nathan Cooley Keep in the history of ether anesthesia.

    Science.gov (United States)

    Guralnick, Walter C; Kaban, Leonard B

    2011-07-01

    In this report, we explore the little known role of Dr Nathan Cooley Keep in the dissemination of ether anesthesia in Boston. Keep was a prominent Boston dentist who, for a short time, taught and employed both William Morton and Horace Wells. He used ether anesthesia for a variety of dental and other surgical procedures requiring pain control. Keep administered ether to anesthetize Henry Wadsworth Longfellow's wife during the delivery of their daughter. This was the first use of ether for obstetric anesthesia. Dr Keep was also the first Dean of the Harvard Dental School and convinced the Massachusetts General Hospital to appoint a dentist to the staff of the hospital for the first time. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

    2017-07-15

    OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

  3. Oral administration of Vaccinium uliginosum L. extract alleviates DNCB-induced atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Kim, Kang-Hyun; Choung, Se-Young

    2014-12-01

    Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that responds to the interplay of environmental, immunological, and genetic factors. To explore the effect of Vaccinium uliginosum (VU) extract on AD, we orally administrated VU total water extract to AD-induced NC/Nga mice. VU extract reduced AD-like skin lesions, ear thickness, and the frequency of scratching episodes in a time-dependent manner. VU also suppressed the levels of IgE and histamine and the ratio of IgG1/IgG2a in the serum of AD-induced NC/Nga mice. VU administration resulted in the reduction of splenic cytokine production, epidermal thickening, and the infiltration of eosinophils, mast cells, and degranulated mast cells induced by 2,4-dinitrochlorobenzene (DNCB). In addition, VU significantly reduced the mRNA expression of chemokine ligands in dorsal skin. Total water extract and subfractions of VU inhibited interleukin (IL)-4 production in splenocytes, suggesting that VU total extract has a Th2 cytokine modulating effect. These results suggest that the VU total water extract could be a candidate therapeutic agent for the treatment of AD through an immunoregulatory effect.

  4. Oral administration of sunitinib malate for long-term survival of a patient with multiple lung metastases from renal leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Li X

    2016-07-01

    Full Text Available Xiaoyan Li, Hongjun Gao, Chuanhao Tang, Xiaoqing Liu Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China Abstract: Sunitinib, an oral tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for the treatment of metastatic renal cell carcinoma and imatinib-refractory gastrointestinal stromal tumor. In non-gastrointestinal stromal tumor soft tissue sarcomas, the activity of this small-molecule drug has been rarely reported. Herein, we report a patient with lung metastases from renal leiomyosarcoma who responded favorably to sunitinib after the failure of conventional chemotherapy. Adverse effects of sunitinib, which include fatigue, hand-foot syndrome, and stomatitis were observed following its administration. Withdrawal of sunitinib led to progression of disease, and resuming use of sunitinib was still effective for multiple lung metastases. Sunitinib might be an effective treatment for renal leiomyosarcoma, especially when conventional chemotherapy fails. Keywords: sunitinib, gastrointestinal stromal tumor, GIST, renal leiomyosarcoma

  5. Effects of Oral Maternal Administration of Caffeine on Reproductive Functions of Male Offspring of Wistar Rats.

    Science.gov (United States)

    Ogunwole, Eunice; Akindele, Opeyemi O; Oluwole, Omobola F; Salami, S A; Raji, Y

    2015-12-20

    Caffeine was investigated for its possible fetal programming effects on reproductive function of male offspring. Sixty-five pregnant Wistar rats were grouped into four. Group 1 was control and received distilled water. Groups 2, 3 and 4 were treated orally with 1.14, 3.42 and 5.70 mg/kg body weight of caffeine respectively. Each group was subdivided into four based on gestation days (GD) 1-7, 8-14, 15-21 and 1-21. The day of parturition was taken as postnatal day zero (0). Male offspring were sacrificed on postnatal day 70. Parameters determined were: weight at birth, body weight at postnatal day 21 and 70, anogenital distance (AGD) index, sperm parameters, reproductive organ weight, histology and hormonal profile (testosterone, FSH and LH). Data were analyzed using Analysis of Variance. Level of significance was taken at Pcaffeine treated dams showed dose dependent significant decreases in birth weight. Male offspring from dams treated with caffeine during GD 1-7 and GD 1-21 had a significant increase in their AGD index. Also, male offspring from dams treated with 1.14 and 5.70 mg/kg body weight of caffeine during GD 8-14 had a significant increase in AGD index. Dams treated with 3.42 mg/kg body weight of caffeine during GD 15-21, had a significant increase in the AGD index of their male offspring. The sperm motility of offspring from dams treated with 5.70 mg/kg body weight of caffeine during GD 1-7 and GD 1-21 were significantly increased. Offspring of GD 8-14 and GD 15-21 dams treated with 3.42 and 5.70 mg/kg body weight of caffeine respectively, showed significantly reduced serum testosterone level. There was a significant decrease in the weight of testes of offspring from dams treated with caffeine during GD 8-14. Histological sections of testes of offspring from caffeine treated dams showed interstitial congestions, edema, reduced germinal epithelial height and detached basal membrane. Maternal caffeine exposure during different gestational periods adversely

  6. Pharmacokinetics of the active antifungal enantiomer, SCH 42427 (RR), and evaluation of its chiral inversion in animals following its oral administration and the oral administration of its racemate genaconazole (RR/SS).

    Science.gov (United States)

    Kim, Hong; Radwanski, Elaine; Lovey, Raymond; Lin, Chin-Chung; Nomeir, Amin A

    2002-05-15

    Genaconazole (SCH 39304) is a potent triazole antifungal agent that is active both orally and topically. Genaconazole is a racemic mixture which contains 50% of the RR (SCH 42427) and 50% of the SS (SCH 42426) enantiomers. The RR isomer accounts for most of the antifungal activity of genaconazole. Serum concentrations of the RR and SS enantiomers were analyzed by a chiral HPLC method which involved extraction of serum with organic solvent followed by separation on a Cyclobond I column and quantification by UV absorbance at 205 nm. The bioavailability and pharmacokinetic profiles of the two enantiomers after oral administration of the racemate (genaconazole) were very similar in cynomolgus monkeys. In rats following dosing with genaconazole, the RR enantiomer had a lower C(max) and a longer t(1/2) than the SS enantiomer, while the AUC(I) values of the two enantiomers were similar. Based on chiral HPLC analysis, there was no evidence for the inversion of the RR to the SR isomer, or of the SS to the SR isomer, indicating that there was no chiral inversion of the RR or SS enantiomers in either species. Genaconazole at 20 mg/kg and the RR (SCH 42427) enantiomer at 10 mg/kg had very similar serum concentration-time profiles and C(max), AUC(I), and t(1/2) values for the RR enantiomer in both rats and monkeys, indicating that the two treatments were equivalent with respect to the bioavailability of the RR enantiomer. Copyright 2002 Wiley-Liss, Inc.

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

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  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. Serum calcium response following oral zinc oxide administrations in dairy cows

    DEFF Research Database (Denmark)

    Thilsing-Hansen, T; Jørgensen, R J; Thilsing, Trine

    2001-01-01

    Six non-pregnant cows were allocated into 3 groups. Group 1 comprised a pair of lactating cows, whereas groups 2 and 3 each comprised a pair of non-lactating cows. The cows in groups 1 and 2 were dosed intraruminally by stomach tube with zinc oxide at 120 mg Zn per kg of bodyweight at weekly...... intervals for a period of 33 days. Each cow received a total of 4 doses of zinc oxide. Group 3 served as non-treated control group. Blood samples were collected from all 6 cows daily. Serum was analysed for concentration of calcium. Within 12-24 h of each zinc oxide administration the serum calcium...... of the hypocalcaemic response decreased with the number of zinc oxide dosings. This effect was explained as a response from the stimulation of the calcium homeostatic mechanisms. In the Zn dosed non-lactating cows responses were similar but less clear. The perspective of these findings is discussed in relation...

  10. 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.

  11. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.

    Science.gov (United States)

    Almon, Einat; Khoury, Tawfik; Drori, Ariel; Gingis-Velitski, Svetlana; Alon, Sari; Chertkoff, Raul; Mushkat, Mordechai; Shaaltiel, Yoseph; Ilan, Yaron

    2017-07-01

    An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels. An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed. An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Online video in clinical skills education of oral medication administration for undergraduate student nurses: a mixed methods, prospective cohort study.

    Science.gov (United States)

    Holland, Agi; Smith, Fiona; McCrossan, Gill; Adamson, Elizabeth; Watt, Susan; Penny, Kay

    2013-06-01

    Improvements in the safety of the prescribing, dispensing and administration of medicines are identified as a priority across international healthcare systems. It is therefore essential that higher education institutions play their part in helping to meet this patient safety objective. New developments in clinical skills education which are aligned to emerging educational theory are available, but evaluations and supportive evidence are limited. To evaluate the use of an online best practice exemplar as an adjunct to the clinical skills teaching of oral medication administration to undergraduate student nurses. Mixed-methods prospective cohort design. Two intakes of undergraduate nursing students (n=168, n=154) undertaking a first year clinical skills based module at a British university. The Control group received standard teaching using lectures and skills classes facilitated by experienced clinical skills lecturers. The Intervention group received the standard teaching and unlimited access to an online video clip of medication administration. Performance and satisfaction were measured using module assessment results and a satisfaction questionnaire. Qualitative data were gathered using focus groups (n=16, n=20). The Intervention group was significantly (p=0.021) more likely to pass the assessment and rate their satisfaction with the teaching significantly higher (pskill was enhanced. An online video of a best practice exemplar as an adjunct to taught clinical skills sessions improves student assessment results and satisfaction ratings. The video was also reported to positively influence all themes identified in Classroom Learning and was perceived to promote the Transfer to Practice of teaching input. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Oral administration of Sauce llorón extract to growing lambs to control gastrointestinal nematodes and Moniezia spp.

    Science.gov (United States)

    Cedillo, J; Kholif, A E; Salem, A Z M; Elghandour, M M Y; Vázquez, J F; Alonso, M U; Barbabosa, A; Chagoyán, J C V; Reyna, A G

    2015-07-01

    To explore anthelmintic effects of oral administration of aqueous extract of Sauce llorón (Salix babylonica; SB) against gastrointestinal nematodes and Moniezia spp. Sixteen Pelibuey male lambs of 3-4 months of age and (23.7 ± 3.3) kg body weight were used in a completely randomized design to be fed a total mixed ration (Control; SB0), or Control plus SB extract using 20 (SB20), 40 (SB40) and 60 (SB60) mL/lamb(/)day for 45 days. Lambs had a natural gastrointestinal nematodes and Moniezia spp. infection and had never been treated with chemical anthelmintic drugs. Individual faecal samples were collected for ova counting using McMaster procedure after 0, 7, 14, 21, 30 and 45 days post extract administration. No extract dose × day interactions for both gastrointestinal nematodes and Moniezia spp. egg count were found. Administration of SB extract had a higher effect (quadratic effect, P = 0.006 4) at dose of 20 mL SB/lamb/day for gastrointestinal nematode eggs during the first 21 days; however, the dose of SB40 tended (linear effect, P = 0.089 7) to be more effective than the others for Moniezia spp. egg during the first 7 days. Sampling day had a linear (P = 0.043 6) effect on Moniezia spp. egg count. The aqueous extract of SB could be more effective against nematodes at 20 and at 40 mL/lamb/day for Moniezia spp. The use of the SB extract could represent a promising alternative to synthetic anthelmintics for the treatment of gastrointestinal nematodes and Moniezia spp. in small ruminants from organic and conventional production systems. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  14. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

    Science.gov (United States)

    Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

    2017-02-01

    This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl 2 ). After 15 days of oral administration of CO (2 ml kg -1 body weight) and MO (2 ml kg -1 body weight) along with intraperitoneal (i.p.) administration of HgCl 2 (5 mg kg -1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl 2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl 2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl 2 (2 ml kg -1 body weight + 5 mg kg -1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl 2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl 2 -induced oxidative damage. © 2016 Blackwell Verlag GmbH.

  15. Efficacy of oral transmucosal and intravenous administration of buprenorphine before surgery for postoperative analgesia in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Ko, Jeff C; Freeman, Lynetta J; Barletta, Michele; Weil, Ann B; Payton, Mark E; Johnson, Brenda M; Inoue, Tomohito

    2011-02-01

    To compare the efficacy of preoperative administration of buprenorphine (via oral transmucosal [OTM] and IV routes) for postoperative analgesia in dogs undergoing ovariohysterectomy. Prospective, randomized, blinded study. 18 dogs undergoing routine ovariohysterectomy. Dogs were allocated to 3 groups (6 dogs/group) and were assigned to receive buprenorphine (20 μg/kg [9.09 μg/lb], IV; a low dose [20 μg/kg] via OTM administration [LOTM]; or a high dose [120 μg/kg [54.54 μg/lb] via OTM administration [HOTM]) immediately before anesthetic induction with propofol and maintenance with isoflurane for ovariohysterectomy. Postoperative pain was assessed by use of a dynamic interactive pain scale. Dogs were provided rescue analgesia when postoperative pain exceeded a predetermined threshold. Blood samples were collected, and liquid chromatography-electrospray ionization-tandem mass spectrometry was used to determine plasma concentrations of buprenorphine and its metabolites. Data were analyzed with an ANOVA. Body weight, surgical duration, propofol dose, isoflurane concentration, and cardiorespiratory variables did not differ significantly among treatment groups. Number of dogs requiring rescue analgesia did not differ significantly for the HOTM (1/6), IV (3/6), and LOTM (5/6) treatments. Similarly, mean ± SEM duration of analgesia did not differ significantly for the HOTM (20.3 ± 3.7 hours), IV (16.0 ± 3.8 hours), and LOTM (7.3 ± 3.3 hours) treatments. Plasma buprenorphine concentration was ≤ 0.60